insulin-glargine and Hypoglycemia

Hypoglycemia and insulin-related adverse events are crucial barriers to effective diabetes management, particularly in the elderly, people with renal impairment, people with diabetes fasting during Ramadan, or people with type 1 diabetes mellitus (T1DM). There is a scarcity of clinical and real-world evidence assessing the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in these special populations. To understand the entirety of evidence, this mini-review elaborates on the use of Gla-300 in diabetes management among special populations.. Clinical and real-world evidence related to the use of Gla-300 among special populations with diabetes were retrieved using PUBMED and Google Scholar.. Gla-300 has shown improved glycemic control with stable insulin action and low risk of hypoglycemia in diverse groups with diabetes. It also appears to have an acceptable safety profile during Ramadan fasting. However, adequate monitoring and adjustment of insulin dose on an individual basis should be considered.. Gla-300 is a second-generation basal insulin with proven benefits of reduced risk of hypoglycemia and improved glycemic control in special populations of people with diabetes.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

To compare the clinical efficacy and safety of glargine-U100 (Lantus/Gla-100) with glargine-U300 (Toujeo/Gla-300) in adult patients with type 2 diabetes (T2D) and type 1 diabetes (T1D).. A literature search on Gla-300/Gla-100 in diabetes management was conducted using the MEDLINE/Embase/Cochrane databases from inception to 10 January 2021. Eligible studies considered for inclusion were parallel-design, randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies. The random-effects model was applied for interpretation of the results.. Of 5348 records screened, 592 were assessed for eligibility and 15 RCTs were considered for data extraction and meta-analysis (T2D [N = 10; n = 7082]; T1D [N = 5; n = 2222]). In patients with T1D, all safety parameters were comparable between Gla-100 and Gla-300. In T2D, statistically significant differences were observed in favour of Gla-300 over Gla-100 for nocturnal and total hypoglycaemia. For efficacy parameters, a statistically and clinically significant difference favouring Gla-100 in basal insulin dose requirement was observed for both T2D and T1D. Change in HbA1c showed a statistically but not clinically significant reduction with Gla-100 compared with Gla-300 in T1D. Statistically significant but clinically less relevant differences favoured Gla-300 for control of body weight in T1D and T2D and Gla-100 for fasting blood glucose in T2D.. Gla-100 and Gla-300 had comparable efficacy and safety profiles in both T1D and T2D populations. Gla-300 showed a lower risk of nocturnal and total hypoglycaemia, significant in insulin-experienced/exposed patients with T2D. Patients on Gla-300 required significantly more units of insulin daily than the Gla-100 group to achieve equivalent efficacy.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Regular, Human; Treatment Outcome

Insulin therapy should ideally mimic a basal-bolus pattern. Lente, NPH, NPH/regular mixes, PZI, glargine U100, and detemir are intermediate-acting formulations that are administered twice daily in dogs. To minimize hypoglycemia, intermediate-acting insulin protocols are usually geared towards alleviating (but not eliminating) clinical signs. Insulin glargine U300 and insulin degludec meet the criteria for an effective and safe basal insulin in dogs. In most dogs, good control of clinical signs is achieved when using a basal insulin alone. In a small minority, bolus insulin at the time of at least one meal per day may be added to optimize glycemic control.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

Our aim in this study was to compare the efficacy and safety of commercially available fixed-ratio combinations (FRCs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and basal insulins by a network meta-analysis of randomized controlled trials (RCTs) of people with type 2 diabetes.. We present a systematic review and network meta-analyses of RCTs of individuals with type 2 diabetes randomized to FRCs or to their components for ≥24 weeks. All reports were obtained from PubMed or ClinicalTrials.gov up to February 28, 2022. The primary outcome was glycated hemoglobin (A1C) level attained. Secondary outcomes included fasting plasma glucose, change in body weight, and incident hypoglycemia. Treatment effects were estimated as mean difference (MD) and standard error (SE), or as odds ratio (OR) with 95% confidence interval (CI) using the fixed combination of insulin glargine 100 IU/mL and lixisenatide (iGlarLixi) as reference.. We included 29 RCTs from among the 1,404 articles identified. No direct comparisons between FRCs were found. After excluding some insulin-capped trials to reach model consistency, both FRCs were more efficacious regarding A1C than their components, but no difference between FRCs was found (MD, -0.10%; SE, 0.10%). The effect of the fixed combination of insulin degludec and liraglutide (IDegLira) (MD, -0.47 mmol/L; SE, 0.24 mmol/L) and basal insulins was similar to that of iGlarLixi (reference) on fasting glucose, whereas GLP-1RAs had lower efficacy than iGlarLixi. Weight gain was lower with GLP-1RAs and IDegLira (MD, -0.72 kg; SE, 0.32 kg) than with iGlarLixi (reference) and higher with basal insulins. Incident hypoglycemia (based on different definitions) was least frequent with GLP-1RAs, followed by IDegLira (OR, 0.78; 95% CI, 0.39 to 1.57), iGlarLixi (reference), and basal insulins.. For A1C, both FRCs were more efficacious over their individual components, with similar efficacies of the 2 FRCs.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Liraglutide; Network Meta-Analysis; Randomized Controlled Trials as Topic

To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin-naïve patients with type 2 diabetes mellitus.. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO.. Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta-analyses and network meta-analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U-300 or degludec U-100, glargine U-100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U-100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin < 7.0%) and lead to fewer hypoglycemic events than injecting it at bedtime. The optimal starting dose for the initiation of any basal insulins can be 0.10-0.20 U/kg/day. There is no eligible evidence to investigate the optimal maintenance dose for basal insulins.. The five basal insulins are effective for the target population. Glargine U-300, degludec U-100, glargine U-100, and detemir lead to fewer hypoglycemic events than NPH without compromising glycemic control.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

To compare the efficacy and safety of insulin glargine-300 once daily (Gla-300) with insulin degludec/aspart (IDegAsp) once daily in patients with type 2 diabetes (T2D) inadequately controlled on oral anti-diabetic drugs (OADs).. A systematic literature review of randomized controlled trials was followed by an indirect treatment comparison of studies involving insulin naïve adults, inadequately controlled [glycated haemoglobin (HbA1c) ≥7.0%] on OADs, who received Gla-300 or IDegAsp once daily. Outcomes of interest were change in HbA1c, blood glucose, weight and insulin dose, as well as incidence and event rate of hypoglycaemia and other adverse events.. Four trials with broadly similar baseline patient characteristics were included in the meta-analyses and indirect treatment comparison. At 24-28 weeks, the indirect comparison of Gla-300 to IDegAsp once daily estimated no statistically significant difference for change in HbA1c (%) from baseline [mean difference of 0.10% (95% CI: -0.20, 0.39; p = .52)]; a statistically significant mean difference of -1.31 kg (95% CI: -1.97, -0.65; p < .05) for change in body weight from baseline; statistically significant odds ratios of 0.62 (95% CI: 0.41, 0.93; p < .05) for incidence of any hypoglycaemia; and 0.47 (95% CI: 0.25, 0.87; p < .05) for incidence of anytime confirmed hypoglycaemia (plasma glucose <3.0-3.1 mmol/L). No significant differences were observed for insulin dose and adverse events.. In insulin-naïve patients with T2D inadequately controlled on OADs, commencing Gla-300 shows a comparable HbA1c reduction, but with significantly less weight gain and a lower incidence of any and confirmed hypoglycaemia compared with commencing IDegAsp.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Regular, Human

Recent studies have found compared with insulin glargine (IGlar), insulin degludec/aspart (IDeg/Asp) may provide adequate glycemic control and prevent hypoglycemia events in type 2 diabetes mellitus (T2DM). Consequently, we performed a meta-analysis to appraise and compare the efficiency and safety of IDeg/Asp and IGlar in the treatment of T2DM. We sought the databases including PubMed, Embase, Scopus, Cochrane library to confirm related articles which inspected the effect of IDeg/Asp versus IGlar for the treatment of T2DM until May 2021. Finally, six randomized controlled trials (RCTs) of 1,346 patients were included. The results showed that IDeg/Asp significantly decreased the mean hemoglobin A1c (HbA1c) level but was prone to serious adverse events, and IGlar increased the nocturnal confirmed hypoglycemia events. Besides, there were no significant changes in other indicators, including mean fasting plasma glucose (FPG) level, nine-point self-measured plasma glucose (SMPG) level, and adverse events. What's more, we found that there was no significant difference in the occurrence of hypoglycemia overall, but our subgroup analysis of confirmed hypoglycemia revealed the population in this subgroup (duration of diabetes ≤11 years) might has its particularity effecting the hypoglycemia outcome. Concerning efficiency, IDeg/Asp may have advantages in controlling the mean HbA1c level. Regarding safety, IGlar might increase the risk of nocturnal confirmed hypoglycemia. Further evidence is needed to compare better the efficiency and safety of IDeg/Asp versus IGlar therapy.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Clinical differences between degludec U100 (Deg-100) and glargine U300 (Gla-300) in type 1 diabetes (T1D) were unknown.. To indirectly compare the safety, efficacy, and cost-effectiveness between Deg-100 and Gla-300 in T1D adults via systematic review.. Medline, the Cochrane Library, ClinicalTrials.gov, and Google Scholar were searched (October 2021). Randomized controlled trials comparing Deg-100 or Gla-300 vs. glargine U100 in T1D adults (follow-up ≥ 12 weeks) were selected and analyzed using a frequentist network meta-analysis. Cost-effectiveness analysis (CEA) was conducted over a 1-year time horizon from societal perspectives.. Nine trials were included. Efficacy analysis suggested that Deg-100 was non-inferior to Gla-300 in reducing HbA. Low-certainty indirect evidence suggested that Deg-100 appeared to have a favorable reduction in rates of severe hypoglycemia and more cost-effective compared with Gla-300 in T1D adults.

Topics: Adult; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

Performing an updated meta-analysis to compare the safety and efficacy of insulin glargine and insulin detemir in adults with type 1 and type 2 diabetes.. Electronic databases were searched up to 18 August 2021. A random-effects model was applied to pool data from included studies to calculate the standardized mean differences (SMDs) for the continuous variables and relative risks (RRs) for the dichotomous variable.. Nine studies compared insulin detemir and insulin glargine in type 2 diabetes and three studies in patients with type 1 diabetes. The pooled SMD of weight gain was -0.59 (95% CI -1.05 to -0.14; P=0.01; I. It was found that there is no clinically considerable difference between the impacts of insulin detemir and insulin glargine in diabetic patients. The only statistically significant differences were less weight gain in type 2 diabetes and fewer episodes of severe hypoglycemia in type 1 diabetes with insulin detemir.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Weight Gain

The pharmacokinetic and pharmacodynamic properties of the second-generation basal insulin glargine 300 Units/mL (Gla-300) may be of benefit in the treatment of type 1 diabetes mellitus (T1DM). Gla-300 provides a stable and sustained time-action profile, which is associated with glycaemic control and flexible dosing schedule. This review summarises the available evidence on the safety and efficacy of Gla-300 in children and adolescents with T1DM. Gla-300 is as effective as the first-generation basal insulin glargine 100 Units/mL (Gla-100), a standard of care for patients with diabetes in reducing HbA1c, and shows a lower risk of severe hypoglycaemia and hyperglycaemia in children and adolescents with T1DM. However, Gla-300 and Gla-100 are not bioequivalent and are not directly interchangeable. Real-world studies on patients aged 6-17 years are limited. To date, only one small study assessed the effectiveness and safety of Gla-300 versus Gla-100 in newly diagnosed T1DM paediatric patients, confirming the treatment safety and effectiveness of Gla-300 in clinical practice. Gla-300 is a longer-acting basal insulin alternative in the management of children (aged ≥ 6 years) and adolescents with T1DM.. The smooth and prolonged activity of insulin glargine 300 Units/mL (Gla-300), a second-generation basal insulin, results in a stable and sustained glycaemic control while allowing flexible dosing times. In children aged ≥ 6 years and adolescents with type 1 diabetes mellitus (T1DM), Gla-300 provides a glycaemic control comparable to that of glargine 100 Units/mL (Gla-100), a standard of care in patients with T1DM. Gla-300 and Gla-100 show similar safety profiles, with Gla-300 resulting in a clinically relevant trend towards a lower incidence of hyperglycaemia with ketosis and a lower incidence and event rate of severe hypoglycaemia in children and adolescents with T1DM. Overall, these two insulins are similar, but not interchangeable. To the best of our knowledge, only one real-world study has addressed the effectiveness and safety of Gla-300 compared to Gla-100 in newly diagnosed T1DM paediatric patients, and it has shown the therapeutic benefits of Gla-300 in clinical practice.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

Short-term glycemic variability is associated with the risk of hypoglycemia and hyperglycemia in people living with type 1 diabetes and can potentially affect clinical outcomes. Continuous glucose monitoring (CGM) is of increasing importance to evaluate glycemic variability in greater detail. Specific metrics for assessing glycemic variability were proposed, such as the SD of mean glucose level and associated coefficient of variation, and time in target glucose range to guide study designs, therapy and allow people with diabetes more transparency in interpreting their own CGM data. Randomized controlled trials (RCT) and real-world evidence provide complementary information about the efficacy/effectiveness and safety of interventions. Insulin glargine 300 U/mL (Gla-300) has a longer lasting and less variable action than insulin glargine U100 (Gla-100) with a lower risk of hypoglycemia. While insulin degludec U100 (iDeg-100) was associated with lower glucose values but more time below range in one randomized study compared with Gla-300, Gla-300 was associated with a higher per cent time in range, but also above the therapeutic range. However, a real-world study did not find differences during the day between Gla-300 and iDeg-100. The upcoming InRange RCT is the first head-to-head comparison of Gla-300 with iDeg-100 using CGM in an international population using CGM metrics as the primary endpoint. The non-interventional COMET-T real-world study will determine the real-world effectiveness of Gla-300 using CGM metrics and cover a broad spectrum of clinical practice decisions irrespective of the prior basal insulin.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Randomized Controlled Trials as Topic

Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find out the efficacy and safety of insulin icodec in patients with diabetes mellitus.. We systematically searched the electronic database of PubMed, and Google Scholar from inception until August 20, 2022, using MeSH keywords. Ongoing trials of insulin icodec were additionally searched from the ClinicalTrials.Gov. We retrieved all the available granular details of phase 1 to phase 3 studies of insulin icodec in both type 1 and type 2 diabetes.. Phase 1 study showed insulin icodec having a half-life of 196 h (>1 week) while a steady state is achieved after 3 to 4 weekly injections. Phase 2 studies compared once-weekly icodec to insulin glargine (U-100) and found a similar glucose control with no significantly greater hypoglycemia risks. Top-line results from the five phase 3 studies reported better glucose control with once-weekly icodec compared to both once-daily insulin glargine (ONWARDS 1) and once-daily degludec (in both ONWARDS 2 and 4) with similar rates of hypoglycemia in type 2 diabetes, although there was a higher hypoglycemic event with insulin icodec in type 1 diabetes (ONWARDS 6) compared to once-daily degludec despite a similar glycemic control.. A brighter prospect of once-weekly insulin icodec is on the card in particular in type 2 diabetes in terms of reducing injection pricks by >85% vs. once-daily basal insulin analogs, although few unknowns still exist.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

To examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus (T1DM).. Systematic review and individual patient data (IPD) network meta-analysis (NMA).. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through June 2015.. Randomised controlled trials (RCTs) on adults with T1DM assessing glycosylated haemoglobin (A1c) and severe hypoglycaemia in long-acting and intermediate-acting insulin regimens.. We requested IPD from authors and funders. When IPD were not available, we used aggregate data. We conducted a random-effects model, and specifically a one-stage IPD-NMA for those studies providing IPD and a two-stage IPD-NMA to incorporate those studies not providing IPD.. We included 28 RCTs plus one companion report, after screening 6680 titles/abstracts and 205 full-text articles. Of the 28 RCTs, 27 studies provided data for the NMA with 7394 participants, of which 12 RCTs had IPD on 4943 participants. The IPD-NMA for A1c suggested that glargine once daily (mean difference [MD]=-0.31, 95% confidence interval [CI]: -0.48 to -0.14) and detemir once daily (MD=-0.25, 95% CI: -0.41 to -0.09) were superior to neutral protamine Hagedorn (NPH) once daily. NPH once/two times per day improved A1c compared with NPH once daily (MD=-0.30, 95% CI: -0.50 to -0.11). Results regarding complications in severe hypoglycaemia should be considered with great caution due to inconsistency in the evidence network. Accounting for missing data, there was no evidence of inconsistency and long-acting insulin regimens ranked higher regarding reducing severe hypoglycaemia compared with intermediate-acting insulin regimens (two-stage NMA: glargine two times per day SUCRA (Surface Under the Cumulative Ranking curve)=89%, detemir once daily SUCRA=77%; one-stage NMA: detemir once daily/two times per day SUCRA=85%). Using multiple imputations and IPD only, complications in severe hypoglycaemia increased with diabetes-related comorbidities (regression coefficient: 1.03, 95% CI: 1.02 to 1.03).. Long-acting insulin regimens reduced A1c compared with intermediate-acting insulin regimens and were associated with lower severe hypoglycaemia. Of the observed differences, only glargine once daily achieved a clinically significant reduction of 0.30%. Results should be interpreted with caution due to very low quality of evidence.. CRD42015023511.

Topics: Adult; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Network Meta-Analysis

The goal of this study was to compare the efficacy and tolerability of insulin degludec with those of other long-acting insulin analogues (insulin glargine and insulin detemir) in patients with type 1 or 2 diabetes mellitus (T1D or T2D).. Those randomized controlled trials comparing insulin degludec with other long-acting insulin analogues in the treatment of patients with T1D or T2D published on or before August 21, 2022, were retrieved from PubMed, Web of Science, the Cochrane Library, and EMBASE. The efficacy end points were the changes from baseline in hemoglobin A. Data from a total of 20 trials (19,048 patients) were included. The differences in the reductions in glycosylated hemoglobin between insulin degludec and other long-acting basal insulin analogues (insulin glargine and insulin detemir) used for the treatment of patients with T1D or T2D were not significant. However, the reduction in FPG was greater with insulin degludec (-0.370 mmol/L; 95% CI, -0.473 to -0.267 mmol/L; P ≤ 0.001). Throughout the treatment periods of all of the available trials, the estimated rate ratios of overall and nocturnal hypoglycemia were significantly decreased with insulin degludec compared with insulin glargine or insulin detemir in patients with T1D or T2D; the differences in the risks for severe hypoglycemia were not significant.. Compared with other long-acting insulin analogues (insulin glargine and insulin detemir), insulin degludec was associated with a significantly decreased FPG, with lower prevalences of overall and nocturnal hypoglycemia.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

Hypoglycemia, the condition of low blood sugar, is a common occurance in people with diabetes using insulin therapy. Protecting against hypoglycaemia by engineering an insulin preparation that can auto-adjust its biological activity to fluctuating blood glucose levels has been pursued since the 1970s, but despite numerous publications, no system that works well enough for practical use has reached clinical practise.. This review will summarise and scrutinise known approaches for producing glucose-sensitive insulin therapies. Notably, systems described in patent applications will be extensively covered, which has not been the case for earlier reviews of this area.. The vast majority of published systems are not suitable for product development, but a few glucose-sensitive insulin concepts have recently reached clinical trials, and there is hope that glucose-sensitive insulin will become available to people with diabetes in the near future.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Glucose Transporter Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Polymers

Treatment of type 2 diabetes (T2D) requires progressive therapy intensification to reach and maintain individualized glycemic targets. iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide (Lixi), has been shown to provide robust HbA

Topics: Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020.. We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM.. Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument.. We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-cert. Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.

Topics: Adolescent; Adult; Bias; Child; Child, Preschool; Confidence Intervals; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Myocardial Infarction; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Young Adult

One of the effective and consistent ways to achieve glycaemic control for patients with type 2 diabetes mellitus (T2DM) is once-daily basal insulin. But it is also associated with adverse outcomes such as hypoglycaemia. Dulaglutide, a novel long-acting GLP-1 receptor agonist, may be a more suitable therapy. The present meta-analysis aims to assess the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide compared with insulin glargine for the treatment of T2DM.. We searched PubMed, Embase and Cochrane Library from inception to December 2020. Randomized clinical trials comparing dulaglutide with insulin glargine in adults with T2DM were included. Revman5.2 software was used for meta-analysis.. We included 5 studies with 3383 randomized participants. Compared with insulin glargine, dulaglutide 1.5 mg led to greater mean HbA1c reduction (MD = -0.33%, 95% CI = -0.52, -0.15) whereas dulaglutide 0.75 mg did not (MD = -0.21%, 95% CI = -0.43, 0.01). Body weight loss was seen with dulaglutide whereas weight gain was seen with insulin glargine. The risk of hypoglycaemia was lower in dulaglutide 0.75 mg and 1.5 mg groups than in insulin glargine group,whereas dulaglutide had a statistically higher gastrointestinal adverse events incidence than insulin glargine.. Compared with insulin glargine, dulaglutide may serve as an effective alternative to provide improvement in glycaemic control with weight loss and less hypoglycaemia in patients with T2DM. It may be a more suitable therapy instead of basal insulin.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Immunoglobulin Fc Fragments; Insulin Glargine; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Weight Gain; Weight Loss

Evidence from randomized controlled trials (RCTs) has shown that second-generation basal insulin (BI) analogues, insulin glargine 300 U/mL (Gla-300) and insulin degludec (IDeg), provide similar glycaemic control, with a lower risk of hypoglycaemia compared with the first-generation BI analogue insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes (T2D). However, the highly selected participants and frequent follow-up of RCTs may not be truly representative of real-life clinical practice. It is important to assess the safety and effectiveness of these second-generation BI analogues in real-life clinical practice settings. The DELIVER programme utilized electronic healthcare records from the United States to compare clinical outcomes in people with T2D who received either Gla-300 or other BI analogues in real-world clinical practice. This review provides a concise overview of the results of the DELIVER studies. Overall, Gla-300 provided similar antihyperglycaemic effectiveness and a lower risk of hypoglycaemia versus the first-generation BI analogues Gla-100 and insulin detemir in people with T2D who had switched BIs. In those who were insulin-naïve, initiation with Gla-300 versus Gla-100 was associated with significantly better antihyperglycaemic effectiveness and similar or lower hypoglycaemic risk. Both glycaemic control and hypoglycaemia risk were also shown to be similar with Gla-300 and IDeg, in people who had switched BIs and in those who were insulin-naïve. In addition, the DELIVER 2 study reported that people with T2D who switched to Gla-300 had reduced healthcare resource utilization, with an overall saving of US$1439 per person per year compared with those who switched to another BI analogue. Overall, the real-world DELIVER programme showed that the glycaemic control with a low risk of hypoglycaemia observed with Gla-300 in RCTs was also seen in standard clinical practice.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM).. A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100.. Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE): -1.13 (0.05) % and Gla-100: -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference: 0.02%, 95% CI: -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed ≤ 3.9 mmol/L or severe) vs Gla-100 at any time of day or at night (00:00-05:59 h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups.. Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.

Topics: Adult; Aged; Asia, Eastern; Asian People; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Weight Gain

We aimed to assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults.PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with ≥ 12 weeks of follow-up comparing efficacy (HbA

Topics: Adult; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain

NO. Insulin glargine may lead to less patient-reported, symptomatic, and nocturnal hypoglycemia, although overall, there may not be a difference in the risk for severe hypoglycemia orhypoglycemiarelated emergency department (ED) visits and hospitalizations (strength of recommendation [SOR]: B, systematic review of randomized controlled trials [RCTs], individual RCTs, and observational study).

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes).. We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta-analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily.. The absolute changes in HbA. In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat-to-target, which minimize differences in HbA

Topics: Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Network Meta-Analysis; Practice Guidelines as Topic

Severe hypoglycaemia (SH) remains a challenge to people with type 1 diabetes (T1DM), and new-generation basal insulins may improve patient outcomes. This post hoc meta-analysis explored the risk of SH with insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in a pooled population with T1DM from three randomized, multicentre, 6-month similarly designed phase 3 trials: EDITION 4, EDITION JP 1 and EDITION JUNIOR. Endpoints included incidence and time to first occurrence of SH. Among 629 and 626 participants randomized to Gla-300 and Gla-100, respectively, glycated haemoglobin reductions were similar. Fewer participants experienced ≥1 SH event with Gla-300 (6.2%) than with Gla-100 (9.3%). From baseline to month 6, the risk of a first SH event was lower with Gla-300: hazard ratio 0.65 [95% confidence interval (CI) 0.44-0.98; stratified log-rank test P = 0.038]. SH event rates were numerically lower with Gla-300 versus Gla-100 from baseline to month 6 [relative risk (RR) 0.80 (95% CI 0.49-1.29); P = 0.356] and baseline to week 8 [RR 0.73 (95% CI 0.37-1.44); P = 0.369]. Thus, Gla-300 demonstrated similar glycaemic control with lower risk of SH versus Gla-100, particularly during the titration period.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Risk

Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017.. To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation.. We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion.. Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).. Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I. The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.

Topics: Adamantane; Bias; Cause of Death; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Fasting; Glycated Hemoglobin; Graft Survival; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Kidney Transplantation; Nitriles; Pioglitazone; Postoperative Complications; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Transplant Recipients; Vildagliptin

Approximately 50% of patients with type 2 diabetes mellitus (T2DM) do not achieve glycemic targets and require treatment intensification. A fixed-ratio combination of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin, such as lixisenatide with insulin glargine (iGlarLixi), exploits the complementary mechanisms of action of each component to address hyperglycemia while mitigating potential adverse events (AEs). The iGlarLixi dose is titrated considering the effect of basal insulin on fasting plasma glucose, and the fixed-ratio combination ensures that the lixisenatide dose never exceeds 20 μg/day. We describe the characteristics of iGlarLixi therapy, based on the LixiLan clinical program, and provide guidance on the characteristics of patients likely to benefit from such treatment in routine clinical practice. In the phase III LixiLan trials, iGlarLixi resulted in significantly greater reductions in glycated hemoglobin (HbA1c), better achievement of HbA1c targets, less glycemic variability versus insulin glargine, lixisenatide or GLP-1 RA alone, and was associated with weight control, less hypoglycemia versus insulin glargine, and fewer GI AEs versus lixisenatide. Findings were consistent regardless of age, diabetes duration, and baseline HbA1c. The efficacy, safety, and convenient once-daily administration schedule of iGlarLixi make it a valuable treatment option for patients with T2DM requiring treatment intensification.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Combinations; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Glycemic Control; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Peptides

Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer insulin analogues may result in fewer macrovascular and microvascular events.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues (insulin glargine U100 and U300, insulin detemir and insulin degludec) with NPH (neutral protamine Hagedorn) insulin (human isophane insulin) in adults with type 2 diabetes mellitus.. For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions.. We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)long-acting insulin analogues to NPH in adults with type 2 diabetes mellitus.. Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses.. We identified 24 RCTs. Of these, 16 trials compared insulin glargine to NPH insulin and eight trials compared insulin detemir to NPH insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to insulin glargine and 1321 people to insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing insulin glargine to NPH insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing insulin detemir to NPH insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Changes in HbA1c were comparable for long-acting insulin analogues and NPH insulin. Insulin glargine compared to NPH insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with insulin detemir compared to NPH insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such. While the effects on HbA1c were comparable, treatment with insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Treatment with insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with insulin detemir instead of NPH insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.

Topics: Bias; Diabetes Mellitus, Type 2; Hemoglobin A; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Ever since the discovery of insulin a century ago, relentless attempts have been made to develop insulins that closely mimic the timeaction- profile of human physiologic insulin. The early basal insulins like neutral protamine Hagedorn (NPH), were intermediate-acting, with high risk of hypoglycemia. These primary limitations led to attempts at developing improved basal insulins with a longer duration of action. After several attempts at prolonging insulin action using phenol and structural modifications of the insulin hexamer, insulin glargine was developed in 1988. The superior and unique pharmacological properties, longer duration of action, and significantly lowered risk of hypoglycemia enabled insulin glargine to be distinguished from NPH as a better basal insulin, providing holistic glycemic control. The present review highlights the circumstances that led to the search of truly basal insulins, focusing on the journey of insulin glargine 100 U/mL (Gla-100).

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Fueled by perceptions regarding Indian dietary patterns and premixed insulin's claim to fame of providing dual fasting and post-prandial control, there was a greater inclination towards using premixed insulins in clinical practice until the last decade. However, the advent of insulin glargine 100 U/mL (Gla-100) opened up a new dimension in insulin therapy landscape in India. The data from the last 5 years reveal that Gla-100 has gained more traction among Indian clinical practitioners. Basis evidences that have emerged from various clinical studies, this present review elaborates on certain key issues which have helped Gla-100 carve its own niche and effected a progressive shift in insulin prescription pattern in India.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin; Insulin Glargine; Insulins

The EDITION trials in type 2 diabetes demonstrated comparable glycaemic control with less nocturnal and anytime (24-hour) hypoglycaemia for insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100). However, the predefined nocturnal window (0:00-5:59 AM) may not be the most relevant for clinical practice. This post-hoc analysis compared expansions of the predefined nocturnal interval during basal insulin treatment without prandial insulin. Patient-level, 6-month data, pooled from the EDITION 2 and 3 trials and the EDITION JP 2 trial (N = 1922, basal insulin only) were analysed. Accompanying hypoglycaemia during treatment with Gla-300 was compared to that during treatment with Gla-100, using predefined (0:00-5:59 AM) and expanded (10:00 PM-5:59 AM, 0:00-7:59 AM, 10:00 PM to pre-breakfast SMPG) windows. Confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 6:00 AM and 8:00 AM. Windows expanded beyond 6:00 AM included more events than other windows. The percentage of participants with at least one event was lower with Gla-300 than Gla-100 in all windows examined. Expanding the nocturnal interval allows better assessment of the risk of hypoglycaemia associated with basal insulin. The risk of nocturnal hypoglycaemia was consistently lower with Gla-300 versus Gla-100 using all four windows.

Topics: Adult; Circadian Rhythm; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Time Factors

Second-generation basal insulin analogues (e.g. insulin degludec, insulin glargine 300 U/mL), were designed to further extend the duration of insulin action and reduce within-day and day-to-day variability, and consequently hypoglycaemia risk, versus earlier long-acting basal insulins. This review examines the pharmacokinetic/pharmacodynamic characteristics of insulin degludec (100, 200 U/mL) and insulin glargine (100, 300 U/mL), and their influence on clinical outcomes.. Available pharmacokinetic/pharmacodynamic publications comparing insulin degludec and insulin glargine were reviewed.. Both insulin degludec and insulin glargine 300 U/mL have more prolonged and stable pharmacokinetic/pharmacodynamic profiles than the earlier basal insulin analogue, insulin glargine 100 U/mL. Insulin glargine 300 U/mL (0.4 U/kg, morning) showed a more stable pharmacodynamic profile (20% lower within-day variability [P = 0.047]) and more even 24-h distribution (over each 6-h quartile) than insulin degludec 100 U/mL, whereas the supratherapeutic 0.6 U/kg dose demonstrated a similar, albeit non-significant, trend. In contrast, a second clamp study indicated lower day-to-day variability in the 24-h glucose-lowering effect (variance ratio 3.70, P < 0.0001), and more even dosing over each 6-h quartile, with insulin degludec 200 U/mL versus insulin glargine 300 U/mL (0.4 U/kg, evening). Methodological differences and differences in bioequivalence that may explain these discrepancies are discussed.. Compared with earlier insulin analogues, second-generation basal insulins have improved pharmacokinetic/pharmacodynamic profiles that translate into clinical benefits, primarily reduced nocturnal-hypoglycaemia risk. Additional head-to-head comparisons of insulin degludec and insulin glargine 300 U/mL at bioequivalent doses, utilising continuous glucose monitoring and/or real-world evidence, are required to elucidate the differences in their pharmacological and clinical profiles.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Prognosis

To review evidence comparing benefits and harms of long-acting insulins in patients with type 1 and 2 diabetes.. MEDLINE and two Cochrane databases were searched during February 2018. Two authors selected studies meeting inclusion criteria and assessed their quality. Comparative studies of adult or paediatric patients with diabetes treated with insulin degludec, detemir or glargine were included. Meta-analysis was used to combine results of similar studies, and the I. Of 2534 citations reviewed, 70 studies met the inclusion criteria. No statistically significant differences in HbA1c were seen between any two insulins or formulations. Hypoglycaemia was less probable with degludec than with glargine, including nocturnal hypoglycaemia in type 1 (rate ratio 0.68, 95% CI 0.56-0.81) and type 2 diabetes (rate ratio 0.73, 95% CI 0.65-0.82), and severe hypoglycaemia in type 2 diabetes (relative risk 0.72, 95% CI 0.54-0.96). Patients with type 2 diabetes had higher rates of withdrawal because of adverse events when treated with detemir compared with glargine (relative risk 2.1, 95% CI 1.4-3.3). Adults taking detemir gained about 1 kg less body weight than those taking degludec (type 1) or glargine (type 2).. No differences in glycaemic control were seen between insulin degludec, detemir and glargine. Hypoglycaemia was less probable with degludec than glargine, and patients taking detemir gained less body weight than those given degludec or glargine. In type 2 diabetes, withdrawals as a result of adverse events were more probable with detemir than glargine.

Topics: Blood Glucose; Comparative Effectiveness Research; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome; Weight Gain

The recent introduction of the second-generation long-acting analogue insulins degludec and insulin glargine U300 have increased the choice of basal insulin therapy for patients with type 2 diabetes. The pharmacokinetic and pharmacodynamic properties of these insulins result in a flatter profile that lasts over 24 h and provides an increased window of administration of 6 h once daily. Large-scale multicentre randomised clinical trial programmes (BEGIN for degludec U100 and U200 and EDITION for glargine U300) evaluating these insulin therapies against glargine U100 have demonstrated that they are either non-inferior or superior for glycaemic efficacy and safety, but less likely to result in severe or nocturnal hypoglycaemia than glargine U100. The disposable pen devices for these insulins have been designed with patient satisfaction and convenience in mind. No concerns have arisen with adverse events with insulin analogues or cardiovascular safety from the ORIGIN and DEVOTE trials. As they demonstrate equivalent glycaemic efficacy to other basal insulins, they should be considered more in selected patient groups including those with recurrent or increased risk of hypoglycaemia, especially severe or nocturnal episodes, in the elderly or those living alone, and in patients with multiple co-morbidities such as cardiovascular or renal disease.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome

Diabetes during pregnancy has been linked to unfavorable maternal-fetal outcomes. Human insulins are the first drug of choice because of the proven safety in their use. However, there are still questions about the use of insulin analogs during pregnancy. The objective of the present study was to determine the effectiveness of insulin analogs compared with human insulin in the treatment of pregnant women with diabetes through a systematic review with meta-analysis. The search comprised the period since the inception of each database until July 2017, and the following databases were used: MEDLINE, CINAHL, EMBASE, ISI Web of Science, LILACS, Scopus, SIGLE and Google Scholar. We have selected 29 original articles: 11 were randomized clinical trials and 18 were observational studies. We have explored data from 6,382 participants. All of the articles were classified as having an intermediate to high risk of bias. The variable that showed favorable results for the use of insulin analogs was gestational age, with a mean difference of - 0.26 (95 % confidence interval [CI]: 0.03-0.49;. Diabetes durante a gestação tem sido relacionado a desfechos materno-fetais desfavoráveis. As insulinas humanas são a primeira escolha medicamentosa, devido à comprovada segurança no seu uso. Entretanto, ainda há questionamentos sobre o uso dos análogos da insulina na gestação. O objetivo do presente estudo foi determinar a efetividade dos análogos da insulina comparados às insulinas humanas no tratamento de gestantes com diabetes por meio de uma revisão sistemática com metanálise. A busca compreendeu desde o início de cada base de dados até julho de 2017, e foi realizada nos seguintes bancos de dados: MEDLINE, CINAHL, EMBASE, ISI Web of Science, LILACS, Scopus, SIGLE e Google Scholar. Selecionamos 29 artigos originais, sendo 11 ensaios clínicos randomizados e 18 estudos observacionais. Exploramos dados de 6.382 participantes. Todos os artigos foram classificados como sendo de intermediário a alto risco de viés. A variável que demonstrou resultado favorável ao uso dos análogos da insulina foi idade gestacional, com uma diferença média de - 0.26 (95% índice de confiança [IC]: 0.03–0.49;

Topics: Abortion, Spontaneous; Birth Weight; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Macrosomia; Gestational Age; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Observational Studies as Topic; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic; Treatment Outcome

To investigate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) over 12 months in a patient-level meta-analysis, using data from the EDITION studies in people with type 2 diabetes (T2DM).. EDITION 1, 2 and 3 were multicentre, randomized, open-label, 2-arm, parallel-group, treat-to-target phase IIIa studies. Similar study designs and endpoints enabled a meta-analysis to be conducted.. Reductions in glycated haemoglobin (HbA1c) were better sustained over 12 months with Gla-300 than with Gla-100 (least squares [LS] mean difference in change from baseline: -0.10 % [95% confidence interval {CI} -0.18 to -0.02] or -1.09 mmol/mol [95% CI -2.01 to -0.20]; P = .0174). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycaemia was 15% lower with Gla-300 vs Gla-100 at night (relative risk 0.85 [95% CI 0.77-0.92]) and 6% lower at any time of day (relative risk 0.94 [95% CI 0.90-0.98]). Rates of hypoglycaemia were 18% lower with Gla-300 vs Gla-100 at night (rate ratio 0.82 [95% CI 0.67-0.99]), but comparable at any time of day. HbA1c <7.0 % without nocturnal hypoglycaemia was achieved by 24% more participants with Gla-300 than with Gla-100 (relative risk 1.24 [95% CI 1.03-1.50]). Severe hypoglycaemia was rare; in both treatment groups the incidence of events at any time of day was ≤3.6%, while rates were ≤0.08 events per participant-year.. In a broad population of people with T2DM over 12 months, use of Gla-300 provided more sustained glycaemic control and significantly lower hypoglycaemia risk at night and at any time of day compared with Gla-100.

Topics: Body Weight; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities.. A systematic review of multiple databases including Medline, LILACS, Cochrane, and EMBASE databases with several combinations of agreed terms involving randomized controlled trials and cohorts, as well as manual searches and gray literature, was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed.. Eight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (two generic, two mixed, and four specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores, whether as part of subsets or combined into a single score, with the use of GLA versus neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin, but not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the cohort studies scored a maximum on the Newcastle-Ottawa scale for quality, and they generally were of moderate quality with bias in the studies.. There was no consistent difference in QoL or patient-reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings.

Topics: Blood Glucose; Brazil; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Patient Satisfaction; Quality of Life

To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs.. A post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, open-label, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use.. Of 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups.. Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use.. ClinicalTrials.gov NCT01499095; NCT01676220.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

To determine the safety and efficacy of insulin degludec versus glargine in patients with type 1 (T1D) and type 2 (T2D) diabetes mellitus.. Databases were searched until July 5, 2017. We included randomized controlled trials comparing degludec with glargine in diabetic patients, each with a minimum of 16 weeks of follow-up.. Eighteen trials with 16,791 patients were included. Degludec was associated with a statistically significant reduction in risk for all confirmed hypoglycemia at the maintenance treatment period [estimated rate ratio (ERR) 0.81; 95% confidence interval (CI) 0.72‒0.92; P = 0.001], nocturnal confirmed hypoglycemia at the entire (ERR 0.71; 95% CI 0.63‒0.80; P < 0.001) and maintenance treatment period (ERR 0.65; 95% CI 0.59‒0.71; P < 0.001), all irrespective of the pooled diabetic populations and follow-up durations. The differences in the rate of hypoglycemia were more pronounced in nocturnal period and maintenance period and in T2D than T1D patients. Degludec reduced the incidence of severe hypoglycemia in T2D [ERR 0.65; (0.52; 0.89); P = 0.005] but not T1D patients. HbA1c concentration was slightly higher in degludec over glargine but was not clinically relevant [estimated treatment difference (ETD) 0.03; 95% CI - 0.00 to 0.06%; P = 0.06]. Fasting plasma glucose level was lower in degludec-treated patients (ETD - 0.28 mmol/L; 95% CI - 0.44 to - 0.11 mmol/L; P = 0.001). Several subgroup analyses showed largely consistent findings. The rates of adverse events including total mortality and cardiovascular events were not significantly different between two treatment strategies.. Insulin degludec appears to have better safety in reducing hypoglycemic events with similar efficacy compared with insulin glargine.

Topics: Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome

As Type 2 diabetes progresses, treatment is intensified with additional therapies in an effort to manage hyperglycaemia effectively and therefore avoid complications. When greater efficacy is required, options for injectable treatments include glucagon-like peptide-1 receptor agonists and insulin, which may be added on to oral glucose-lowering treatments. Among individuals receiving long-acting basal insulin as their first injectable treatment, ~40-60% are unable to achieve or maintain their target HbA

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin Glargine; Insulin, Long-Acting; Peptides; Postprandial Period; Treatment Outcome

Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone. Two titratable, fixed-ratio combination therapies, iGlarLixi and IDegLira, that combine basal insulin and a GLP-1 RA in a once-daily subcutaneous injection are currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with T2D. The fixed-ratio combination iGlarLixi combines insulin glargine 100 Units/mL with lixisenatide, while IDegLira combines insulin degludec 100 Units/mL with liraglutide. While these new fixed-ratio combinations contain antihyperglycemic medications that are familiar to most health care providers, there are many questions relating to their use when formulated as a fixed-ratio combination therapy. This article discusses the 'top 10' considerations that health care providers should know about these novel combination therapies as these agents begin to gain an increasing presence in clinical practice.

Topics: Diabetes Mellitus, Type 2; Drug Combinations; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Patient Selection; Peptides; Weight Gain

Topics: Biosimilar Pharmaceuticals; Blood Glucose; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Insulin Glargine; Insulin Lispro

The alarming rise in the number of people living with type 2 diabetes (T2D) presents primary care physicians with increasing challenges associated with long-term chronic disease care. Studies have shown that the majority of patients are not achieving or maintaining glycemic goals, putting them at risk of a wide range of diabetes-related complications. Disease- and self-management programs have been shown to help patients improve their glycemic control, and are likely to be of particular benefit for patients with diabetes dealing with these issues. Anticipatory guidance is an individualized, proactive approach to patient education and counseling by a health-care professional to support patients in better coping with problems before they arise. It has been shown to improve disease outcomes in a variety of chronic conditions, including diabetes. While important at all stages, anticipatory guidance may be of particular importance during changes in treatment regimens, and especially during transition to, and escalation of, insulin-based regimens. The aim of this article is to provide advice to physicians on anticipatory guidance for basal-insulin dosing, focusing on appropriate basal-insulin-dose increase and prevention of potentially deleterious basal-insulin doses, so called overbasalization. It also provides an overview of new treatment options for patients with T2D who are not well controlled on basal-insulin therapy, fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists, and advice on the type of anticipatory guidance needed to ensure safe and appropriate switching to these therapies.

Topics: Counseling; Diabetes Mellitus, Type 2; Disease Management; Drug Combinations; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Patient Education as Topic; Peptides; Self Care; Self-Management

The comparison between long acting insulin analogues (LAIA) and human insulin (NPH) has been investigated for decades, with many randomized controlled trials (RCTs) and systematic reviews giving mixed results. This overlapping and contradictory evidence has increased uncertainty on coverage decisions at health systems level.. To conduct an overview of systematic reviews and update existing reviews, preparing new meta-analysis to determine whether LAIA are effective for T1D patients compared to NPH.. We identified systematic reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia. Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The methodological quality of studies was independently assessed by two reviewers, using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that contained a total of 25 relevant clinical trials. Two reviewers independently abstracted data.. We found evidence that LAIA are efficacious compared to NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR 0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24).. This study design has allowed us to carry out the most comprehensive assessment of RCTs on this subject, filling a gap in diabetes research. Our paper addresses a question that is important not only for decision makers but also for clinicians.

Topics: Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Models, Statistical; Randomized Controlled Trials as Topic; Regression Analysis

In the past decade, there has been much advancement in oral antidiabetic agents, but few changes in insulin therapy. With the addition of the ultra-long-acting insulins, insulin glargine U300 (IGlar 300) and insulin degludec (IDeg 100 and IDeg 200), it is important to understand key aspects in the agents' clinical properties, efficacy, safety, dosing, packaging, and place in therapy.. A literature review was conducted using PubMed database and was limited to English, full-text articles published from January 2000 to January 2018. The following search terms were used: insulin glargine 300, insulin degludec, Toujeo, Tresiba, and ultra-long-acting insulin.. These agents are longer acting with sustained insulin coverage as compared with other basal insulins while having a low potential for hypoglycemia. Efficacy and safety profiles are quite good, and potential for weight gain was similar to IGlar 100.. Depending on the patient's needs, these newer agents may offer some advantages. Insulin glargine U300 and IDeg 200 are concentrated, allowing for administration of large doses by less volume, thereby theoretically improving absorption. For patients needing flexible dosing, IDeg may be beneficial. The ultra-long-acting agents may also be useful if it is suspected that the basal insulin is not lasting the entire day.

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Patient Safety; Prevalence; Weight Gain

The purpose of this study was to compare the efficacy and safety of intensive insulin therapy (premixed insulin lispro vs. insulin glargine) in patients with type 2 diabetes mellitus (T2DM).. MEDLINE, EMBASE, the Cochrane Library, and www.clinicaltrials.gov were systematically searched for randomized clinical trials (RCTs) of patients with T2DM treated with either premixed insulin lispro or insulin glargine for a duration of 24 weeks.. A total of 13 RCTs and 5401 patients were included in this study. In parallel trials and crossover trials, premixed insulin lispro was found to be superior to insulin glargine at reducing glycosylated hemoglobin (HbA1c) (parallel trials: weighted mean difference [WMD] -0.18%; 95% confidence interval [CI] -0.31 to -0.06; P = 0.004; crossover trials: WMD 0.37%; 95% CI -0.51 to -0.23; P < 0.00001). Premixed insulin lispro resulted in more weight gain than insulin glargine (parallel trials: WMD +0.64 kg; 95% CI +0.14 to +1.15; P = 0.01; crossover trials: WMD +0.74 kg; 95% CI +0.19 to +1.29; P = 0.009), and premixed insulin lispro was associated with a higher risk of hypoglycemia than insulin glargine (parallel trials: odds ratio [OR] 1.20; 95% CI 1.06-1.36; P = 0.005; crossover trials: OR 2.24; 95% CI 1.45-3.46; P = 0.0003).. Premixed insulin lispro provides a larger reduction in HbA1c and is associated with a significantly higher risk of hypoglycemia and greater weight gain in patients with T2DM. These findings may be helpful in selecting therapy for individual subjects.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Randomized Controlled Trials as Topic; Weight Gain

To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist.. A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed.. All studies assessing the efficacy and/or safety of iGlarLixi were evaluated.. iGlarLixi has been approved in the United States for glycemic control in people with type 2 diabetes (T2D) inadequately controlled with basal insulin (<60 U/d) or lixisenatide. In clinical trials, iGlarLixi was associated with significantly greater reductions from baseline in glycated hemoglobin A. iGlarLixi is a titratable fixed-ratio combination that shows improved efficacy and comparable or improved safety outcomes relative to its separate constituents, offering an alternative approach to intensification of therapy in T2D.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Peptides; Treatment Outcome

Achieving and maintaining glycemic control is important for people with type 2 diabetes (T2D), to reduce disease-related complications and mortality; however, about half of US patients fail to meet glycemic targets. iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide for once-daily administration, was recently approved by the US Food and Drug Administration for use in adults with T2D inadequately controlled on basal insulin (<60 U daily) or lixisenatide. iGlar and lixisenatide have complementary mechanisms of action, primarily targeting fasting plasma glucose and postprandial plasma glucose, respectively. In the US, iGlarLixi is available in a 3:1 ratio of iGlar and lixisenatide, respectively, across the dosage range of 15-60 U of iGlar and 5-20 µg of lixisenatide.. This study identified phase 3 trials which assessed the efficacy and safety of iGlarLixi. Relevant trials were LixiLan-O, which compared iGlarLixi with iGlar or lixisenatide alone in insulin-naïve patients, and LixiLan-L, which compared iGlarLixi with iGlar alone in insulin-experienced patients.. Patients on iGlarLixi experienced greater A1C reduction and were more likely to achieve A1C <7.0% than its comparators. iGlarLixi mitigated the weight gain associated with iGlar without increasing hypoglycemia risk, and resulted in a lower frequency of gastrointestinal adverse events compared with lixisenatide.. iGlarLixi provides a new approach to therapy intensification in patients with T2D. iGlarLixi showed greater A1C efficacy compared with either iGlar or lixisenatide, mitigating iGlar-associated weight gain, without increasing hypoglycemia risk, and reducing the gastrointestinal side-effects seen with lixisenatide.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Peptides; Postprandial Period; Weight Gain

The best insulin regimen to treat hyperglycemia in hospitalized patients on nutritional support (NS) is unclear.. We searched electronic databases to identify cohort studies or randomized clinical trials in order to evaluate the efficacy of different insulin regimens used to treat hyperglycemia in hospitalized patients on NS on diverse outcomes: mean blood glucose (MBG), hypoglycemia, length of stay in hospital, and mortality.. Seventeen studies from a total of 5,030 were included. Enteral Group included 8 studies; 1,203 patients using rapid, glargine, NPH, or Premix insulin; MBG 108-225 mg/dL; hypoglycemia 0-13%. In indirect meta-analyses, NPH insulin ranked best for glucose control (MD 95% CI -2.50 mg/dL [2.65 to -2.35]). Parenteral Group included 4 studies; 228 patients using regular and glargine or NPH insulin; MBG 137-202 mg/dL; hypoglycemia 0-40%. In meta-analyses comparing regular insulin added to parenteral nutrition bag with glargine, MBG (MD 95% CI -3.78 mg/dL [-11.93 to 4.37]; I2 = 0%) or hypoglycemia frequency (RR 95% CI 1.37 [0.43-4.32]; I2 = 70.7%) did not differ. The description related to hospital length of stay and mortality was inconsistent between groups.. The best insulin regimen to treat hyperglycemia in hospitalized patients on NS has not been established; best results using insulin regimens with NPH in enteral nutrition do not seem to be clinically relevant.

Topics: Blood Glucose; Hospital Mortality; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Isophane; Length of Stay; Nutritional Support; Parenteral Nutrition

Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine. Indeed, NPH insulin remains widely used today despite a frequent need for a twice-daily dosing and a relatively high incidence of hypoglycaemia. The early insulin analogues used post-injection precipitation (insulin glargine U100) or dimerization and albumin binding (insulin detemir) as methods of increasing therapeutic duration. These products approached a 24-hour glucose-lowering effect with decreased variability in insulin action. Newer basal insulin analogues have used up-concentration in addition to precipitation (insulin glargine U300), and multihexamer formation in addition to albumin binding (insulin degludec), to further increase duration of action and/or decrease the day-to-day variability of the glucose-lowering profile. Clinically, the major advantage of these recent analogues has been a reduction in hypoglycaemia with similar glycated haemoglobin control when compared with earlier products. Future therapies may bring clinical benefits through hepato-preferential insulin receptor binding or very long durations of action, perhaps enabling once-weekly administration and the potential for further clinical benefits.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Lente; Insulin, Long-Acting; Recombinant Proteins

Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins.. MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies.. Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted.. Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Incretins; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Peptides; Recombinant Fusion Proteins; Venoms

Older adults are at an increased risk of developing type 2 diabetes mellitus (T2DM). Although oral agents (i.e., metformin) are the preferred first-line therapy, older adults often eventually require the addition of insulin to control their blood glucose. Long-acting insulin analogues are the preferred insulin products for older adults with T2DM. Insulin degludec and insulin glargine U-300 are both new generation long-acting insulins. When compared with the standard of care, long-acting insulin product insulin glargine U-100, insulin degludec, and insulin glargine U-300 had similar glucose-lowering effects, longer half-lives and durations of action, and a more even distribution over a 24-hour period. Additionally, the new generation insulins were superior with regard to rates and severity of nocturnal hypoglycemia. The long-term cardiovascular safety of these products has not been established yet. Although the new generation long-acting insulins will not revolutionize diabetes management, they appear to be an improvement over previous long-acting insulins.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily.. Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose.. Mean HbA1c and FPG reductions were similar with Gla-100 and NPH insulin regardless of concomitant OAD (P=0.184 and P=0.553, respectively) and similar proportions of subjects achieved HbA1c <7.0% (P=0.603). There was a trend for more subjects treated with Gla-100 achieving FPG ⩽100mg/dL versus NPH insulin (relative risk [RR] 1.09 [95% confidence interval (CI) 0.97-1.23]; P=0.135). Plasma glucose confirmed (<70mg/dL) overall and nocturnal hypoglycaemia incidences and rates were lower with Gla-100 versus NPH insulin (overall RR 0.93 [95% CI 0.87-1.00]; P=0.041; nocturnal RR 0.73 [95% CI 0.65-0.83]; P<0.001). After 24weeks, weight gain and insulin doses were higher with Gla-100 versus NPH insulin (2.7kg vs 2.3kg, P=0.009 and 0.42U/kg vs 0.39U/kg; P=0.003, respectively). Insulin doses were higher when either insulin was added to sulfonylurea alone.. Pooled results from treat-to-target trials in insulin-naïve people with type 2 diabetes demonstrate a significantly lower overall and nocturnal hypoglycaemia risk across different plasma glucose definitions with Gla-100 versus NPH insulin at similar glycaemic control. OAD therapy co-administered with Gla-100 or NPH insulin impacts glycaemic control and overall nocturnal hypoglycaemia risk.

Topics: Administration, Oral; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Isophane; Male; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Treatment Outcome; Weight Gain

Insulin glargine 300 units/mL: Insulin glargine 300 units/mL (Gla-300) is a formulation of insulin glargine that delivers the same number of insulin units in one-third of the injectable volume of insulin glargine 100 units/mL (Gla-100). Glucose control: Recently approved in the United States and in Europe for use in type 1 and type 2 diabetes, Gla-300 has a more constant and evenly distributed glucose-lowering effect compared with Gla-100, with a duration of action beyond 24 hours and lower within-day and between-day intra-individual variability in blood glucose levels. These benefits translate into predictable and sustained glucose control from a once-daily injection, with potential for fewer hypoglycemia episodes and less weight gain.. Case studies are presented to highlight the potential clinical benefits and considerations associated with initiating treatment with Gla-300 in people with type 1 and type 2 diabetes.

Topics: Diabetes Mellitus; Drug Monitoring; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Treatment Outcome

The goal of this post hoc analysis was to determine key patient and treatment-related factors impacting glycosylated hemoglobin (A1C) and hypoglycemia in patients with uncontrolled type 2 diabetes who were initiated to basal insulin (neutral protamine Hagedorn [NPH] or glargine).. Using individual patient-level data pooled from 6 treat-to-target trials, 2600 patients with type 2 diabetes on oral antidiabetic agents initiated to insulin glargine or NPH and treated for 24 to 36 weeks were analyzed.. Both treatments led to significant reduction in A1C levels compared with baseline, with no differences between treatment groups (mean ± standard deviation; glargine: -1.32 ± 1.2% vs NPH: -1.26 ± 1.2%; P = 0.15), with greater reduction in the BMI ≥30 kg/m group than in the BMI <30 kg/m group. Glargine reduced A1C significantly more than NPH in the BMI <30 kg/m group (-1.30 ± 1.18% vs -1.14 ± 1.22, respectively; P = 0.008), but not in the BMI ≥ 30 kg/m group (-1.37 ± 1.19 vs -1.48 ± 1.22, respectively; P = 0.18). Similar proportions of patients achieved A1C target of <7% (glargine 30.6%, NPH 29.1%; P = 0.39). Incidence of severe and severe nocturnal hypoglycemia was significantly lower in glargine versus NPH-treated patients (2.0% vs 3.9%; P = 0.04, and 0.7% vs 2.1%; P = 0.002, respectively), and occurred primarily in the BMI <30 kg/m group.. Initiation of basal insulin is highly effective in lowering A1C after oral antidiabetic agent failure. Glargine decreases A1C more than NPH in nonobese patients, and reduces the risk for severe and severe nocturnal hypoglycemia versus NPH both in obese and nonobese patients, but more so in nonobese patients. Thus, it is the nonobese patients who may benefit more from initiation of basal insulin as glargine than NPH.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Obesity; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Despite improvements in anti-hyperglycemic therapies, there are many unmet clinical needs that hinder successful glycemic control in people being treated with current basal insulin analogs.. This paper reviews the unmet needs associated with current basal insulin therapy and describes the most recent basal insulins for the treatment of diabetes.. PubMed was searched for articles on basal insulin analogs published between 2000 and April 2016.. Although long-acting insulin analogs, such as insulin glargine 100 units/mL and insulin detemir, have come towards approximating physiologic basal insulin levels, limitations such as hypoglycemia and intra- and inter-individual variability are associated with their use resulting in glycemic fluctuations. Some basal insulins lack 24 hour coverage, requiring some patients to split their dose, increasing the number of injections required to maintain glycemic control. Fear of hypoglycemia and the need for additional injections often leads to poor compliance and suboptimal glycemic control. Long-acting insulin analogs, such as insulin glargine 300 units/mL and insulin degludec, have improved upon the shortcomings of the current basal insulin analogs. Improved pharmacodynamic/pharmacokinetic profiles afford lower intra-patient variability and an extended duration of action, providing full and stable 24 hour basal insulin coverage with once daily dosing, and comparable efficacy to insulin glargine with lower rates of hypoglycemia.. The improved pharmacodynamic/pharmacokinetic profiles of new long-acting insulin formulations provide greater glycemic control with once daily dosing. With the growing number of therapeutic choices available, physicians have more scope to individualize patient options for basal insulin therapy.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male

To evaluate the efficacy and safety of adding a single bolus dose of insulin glulisine to basal insulin ('basal-plus') in persons with type 2 diabetes.. Data from patients with poor glycemic control on oral antihyperglycemic drugs who were initiated on a 'basal-plus' regimen for up to 6 months were pooled from four randomized, multicenter studies. Glycated hemoglobin (HbA1c), fasting blood glucose, postprandial glucose (PPG), insulin dose and demographics were measured at baseline and end of study.. 711 patients with a mean age of 59.9 years and a mean duration of diabetes of 11.0 years were included in the analysis population. A 'basal-plus' regimen was associated with significant decreases in HbA1c and PPG at 6 months, an increase in glargine and glulisine doses and small, but statistically significant, changes in body weight and BMI in all patient subsets. The proportion of patients with HbA1c<7% also increased in all populations studied, while the prevalence of severe hypoglycemia was low and did not significantly differ across patient groups.. These results suggest that the use of 'basal-plus' can achieve a good therapeutic response with a low risk of hypoglycemia and weight gain, regardless of a patient's age or BMI.

Topics: Age Factors; Aged; Biomarkers; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

A prospective meta-analysis of phase 3 trials showed lower rates of nocturnal hypoglycaemia with insulin degludec vs. insulin glargine. We investigated the consistency of the results across different definitions of hypoglycaemia.. This post-hoc, patient-level meta-analysis included six randomized, controlled, 26- or 52-week phase 3a trials in insulin-naïve participants with Type 2 diabetes mellitus (Type 2 diabetesinsulin naïve ), participants with Type 2 diabetes mellitus using basal-bolus therapy (Type 2 diabetesBB ) and those with Type 1 diabetes mellitus. We used three definitions of hypoglycaemia and different timescales for the nocturnal period. Rates were analysed for the entire core trial period, the 'maintenance period' only, and the extension trial set population. Analyses utilized a negative binomial regression model.. In Type 2 diabetesinsulin naïve participants, risk of nocturnal hypoglycaemia was significantly lower with insulin degludec vs. insulin glargine for all hypoglycaemia definitions and trial periods. Risk was also lower for the timescale 21.59-05.59, but not 00.01-07.59. For Type 2 diabetesBB , nocturnal hypoglycaemia rates were lower with insulin degludec vs. insulin glargine across all definitions, timescales and trial periods, with one exception. For individuals with Type 1 diabetes mellitus, nocturnal hypoglycaemia risk was significantly lower with insulin degludec during the maintenance period for the original definition (plasma glucose < 3.1 mmol/l, timescale 00.01-05.59) and in the extension trial set population for all hypoglycaemia definitions except for the nocturnal timescale 00.01-07.59.. Compared with insulin glargine, insulin degludec is associated with lower rates of nocturnal hypoglycaemia in people with Type 2 diabetes mellitus, and similar or lower rates in Type 1 diabetes mellitus, across different definitions.

Topics: Circadian Rhythm; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Practice Guidelines as Topic; Precision Medicine; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk

The progressive nature of Type 2 diabetes necessitates treatment intensification over time in order to maintain glycaemic control, with many patients ultimately requiring insulin therapy. While insulin has unlimited potential efficacy, its initiation is often delayed and improvements in glycaemic control are typically accompanied by weight gain and an increased risk of hypoglycaemia, particularly as HbA1c approaches and falls below target levels. This may account for the sub-optimal control often achieved after insulin initiation. Combining insulin with antihyperglycaemic therapies that have a low risk of hypoglycaemia and are weight-neutral or result in weight loss is a therapeutic strategy with the potential to improve Type 2 diabetes management. Although the effects differ with each individual class of therapy, clinical trials have shown that adding a glucagon-like peptide-1 receptor agonist, dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor to insulin regimens can offer a significant reduction in HbA1c without substantially increasing hypoglycaemia risk, or weight. The evidence and merit of each approach are reviewed in this paper. Once-daily co-formulations of a basal insulin and a glucagon-like peptide-1 receptor agonist have been developed (insulin degludec/liraglutide) or are under development (lixisenatide/insulin glargine). Insulin degludec/liraglutide phase III trials and a lixisenatide/insulin glargine phase II trial have shown robust HbA1c reductions, with weight loss and a low risk of hypoglycaemia. With insulin degludec/liraglutide now approved in Europe, an important consideration will be the types of patients who may benefit most from a fixed-ratio combination; this is discussed in the present review, and we also take a look toward future developments in the field.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Combinations; Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Peptides; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

A meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane Library and www. clinicaltrials. gov (up to February 15(th), 2015) were searched. Randomized controlled trials comparing dulaglutide to other drugs for T2DM were collected. Twelve RCTs were included, and the overall bias was low. As the monotherapy, compared with control (placebo, metformin and liraglutide), dulaglutide resulted in a significant reduction in HbA1c (WMD, -0.68%; 95% CI, -0.95 to -0.40), FPG (WMD, -0.90 mmol/L; 95% CI, -1.28 to -0.52), a similar risk of hypoglycemia (7.8% vs. 10.6%), less body weight loss (WMD, 0.51 kg; 95% CI, 0.27 to 0.75). As an add-on intervention with oral antihyperglycemic medication (OAM) and insulin, compared with control (placebo, sitagliptin, exenatide, liraglutide and glargine), dulaglutide lowered HbA1c (WMD, -0.51%; 95% CI, -0.68 to -0.35) and body weight significantly (WMD, -1.30 kg, 95% CI, -1.85 to -1.02) notably, and elicited a similar reduction in FPG (WMD, -0.19 mmol/L; 95% CI, -1.20 to 0.82), an similar incidence of hypoglycemia (24.5% vs. 24.5%). This meta-analysis revealed the use of dulaglutide as a monotherapy or an add-on to OAM and lispro appeared to be effective and safe for adults with T2DM.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin; Insulin Glargine; Liraglutide; Metformin; Patient Safety; Peptides; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Sitagliptin Phosphate; Treatment Outcome; Venoms

To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).. This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO.. Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.. 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings.. NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.

Topics: Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

The common insulin concentration in most preparations of insulin is 100 units per mL or U-100. Human regular U-500 insulin was the first concentrated insulin introduced and it has been available in the United States since the 1950s. Humulin R is the only human regular U-500 available on the market. Human regular U-500 is five times more concentrated than U-100 and because of its pharmacodynamic properties, works as both a basal and a bolus insulin. Human regular U500 allows for delivery of a larger insulin dose with a smaller volume leading to better absorption compared to U-100 and has traditionally been used in patients with moderate to severe insulin resistance. More recently other forms of concentrated insulin have become available and the newer concentrated insulin preparations can be used in diabetic patients with or without insulin resistance. Our intent is to provide primary care physicians with a review of the pharmacology and current literature on concentrated insulins as well as recommendations for patient selection, dose initiation, and dose adjustment.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Compounding; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin Resistance; Insulin, Long-Acting; Patient Selection; Pregnancy; Pregnancy in Diabetics

The purpose of this article is to educate nurse practitioners about the role of Toujeo®, insulin glargine U-300 (Gla-300), which is a new option for the treatment of diabetes mellitus.. A comprehensive literature search was conducted using MEDLINE with the key terms: insulin glargine 300, Toujeo, Gla-300, and EDITION for clinical trial data. Other resources included package inserts, drug information websites, and the World Health Organization (WHO).. Gla-300 appears to be a safe and effective option for basal insulin therapy. In clinical trials, it was shown to be equally efficacious as Gla-100 with fewer episodes of hypoglycemia and slightly less weight gain, and subjects receiving Gla-300 required approximately 10 units more basal insulin to obtain the same hemoglobin A1c (HbA1c) as subjects receiving Gla-100.. This new basal therapy option represents a potential advantage for patients who require higher doses of insulin because of the higher concentration of Gla-300. The lower incidence of hypoglycemia and more predictable pharmacokinetics could offer a significant therapeutic benefit in difficult-to-control patients with diabetes mellitus. The biggest disadvantage of this product is the slightly higher insulin dosage that is required to improve and/or maintain patients' HbA1c.

Topics: Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Weight Gain

A more concentrated insulin glargine formulation, containing 300 U/mL (Gla-300) was approved in 2015 in the US and Europe for the treatment of diabetes mellitus in adults.. This drug evaluation focuses on the pharmacokinetics (PK) and pharmacodynamics (PD) of Gla-300 from studies published up to May 2016. The clinical relevance of this new formulation will be addressed.. Gla-300 was developed to produce a flatter and more prolonged PK/PD profile compared with insulin glargine 100 U/mL (Gla-100) in order to maintain effective glycemic control and reduce the risk of hypoglycemia. Compared to Gla-100, Gla-300 achieves lower and delayed peak concentrations with a PK exposure that is more stable and evenly distributed across a 24-h dosing interval. As a consequence, Gla-300 results in a consistent glucose-lowering effect with less variability over a 24-h dosing interval, which translates to a reduction in the rate of hypoglycemia (particularly nocturnal events).

Topics: Adult; Blood Glucose; Diabetes Mellitus; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

To systematically evaluate the efficacy and safety of insulin degludec for diabetes mellitus (DM).. Databases including Cochrane Library, PubMed, Embase, Wanfang Data, China Biology Medicine disc (CBM) and China National Knowledge Infrastructure (CNKI) were searched electronically for randomized controlled trials (RCTs) meeting including criteria and the methodological quality of studies was assessed. Then meta-analysis was performed using RevMan 5.0 software.. Twelve RCTs with 6 527 patients were included into our study: 4 358 patients in degludec group and 2 169 patients in control group. Compared with insulin glargine, insulin degludec was more effective in reducing fasting blood glucose (MD=-0.40, 95%CI: -0.65--0.16, P=0.001), but less effective in improving levels of glycated hemoglobin (MD=0.13, 95%CI: 0.08-0.17, P<0.001). There was no significant difference in the incidence rate of adverse events in two groups (OR=0.98, 95%CI: 0.87-1.10, P=0.700), but incidence rate of nocturnal hypoglycaemia was significantly lower in insulin degludec group (OR=0.82, 95%CI: 0.72-0.94, P=0.004).. Insulin degludec is non-inferior to other basal insulin in reducing levels of blood glucose, but insulin degludec can obviously reduce the incidence rate of nocturnal hypoglycaemia, so it is safer than other basal insulin. The long-term efficacy and safety should be further studied .

Topics: Blood Glucose; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Safety

Glargine 300 units/ml (Gla-300) is a novel basal insulin formulation approved in 2015 for the treatment of diabetes. This more concentrated form of glargine causes delayed redissolution from the subcutaneous depot after injection and thus altered action profile. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of Gla-300 in patients with type 1 diabetes mellitus (T1DM) will be reviewed. Expert opinion: Gla-300 has a flatter and more prolonged pharmacokinetic profile compared to glargine 100 units/ml (Gla-100), but is less potent on a unit per unit basis. The prolonged duration of Gla-300 should provide 24h coverage with a single daily dose in all patients. Two phase III trials comparing Gla-300 and Gla-100 were conducted in patients with T1DM. A1C reduction and other measures of glycemic control were similar between groups. Hypoglycemia rates were similar among groups in one trial, but favored Gla-300 in the other. Evidence for improvement in hypoglycemia with Gla-300 is more convincing in the type 2 diabetes population. Gla-300 is available in an insulin pen to mitigate potential dosing errors with different glargine concentrations; the maximum dose per injection is 80 units. Future research should include direct comparison with degludec and use in insulin-resistant populations.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom ~3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies. Trials using basal/bolus regimens had higher rates of total hypoglycaemia with BIL due to higher rates of daytime hypoglycaemia. Severe hypoglycaemia rates were similar to comparator among both patients with T1D or type 2 diabetes (T2D). T1D patients lost weight compared with glargine (GL). Patients with T2D tended to gain less weight with BIL than with glargine. Compared to glargine, BIL was associated with higher liver fat, triglycerides and alanine aminotransferase (ALT) levels, including a higher frequency of elevation of ALT ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL. In conclusion, BIL demonstrated better glycaemic control with reduced glucose variability and nocturnal hypoglycaemia but higher triglycerides, ALT and liver fat relative to conventional comparator insulin. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings.

Topics: Alanine Transaminase; Blood Glucose; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Liver; Polyethylene Glycols; Treatment Outcome; Triglycerides; Weight Loss

A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy and safety of insulin glargine (IGlar) and other insulins in T2DM.. A systematic review was carried out in major medical databases up to December 2012. Relevant studies compared efficacy and safety of IGlar, added to oral drugs (OAD) or/and in combination with bolus insulin, with protamine insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events was considered the primary endpoint.. Twenty eight RCTs involving 12,669 T2DM patients followed for 12-52 weeks were included in quantitative analysis. IGlar + OAD use was associated with higher probability of reaching target HbA1c level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR = 1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD demonstrated significantly lower risk of symptomatic hypoglycemia as compared to NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90, 1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63, 0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH, with less frequent adverse events leading to treatment discontinuation than MIX + OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe adverse reactions were less common for IGlar + OAD when compared to MIX + OAD (RR = 0.71 [0.52; 0.98]).. For the majority of examined efficacy and safety outcomes, IGlar use in T2DM patients was superior or non-inferior to the alternative insulin treatment options.

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome

To determine the impact of gender on glycaemic control and hypoglycaemia in insulin-naïve patients with type 2 diabetes (T2DM).. Data were pooled from six randomized clinical trials of insulin glargine or NPH insulin in insulin-naïve, inadequately controlled patients. Female [n = 1251; mean glycated haemoglobin (HbA1c) level 8.99%, age 56.91 years, diabetes duration 9.84 years] and male patients (n = 1349; mean HbA1c 8.9%, age 57.47 years, diabetes duration 10.13 years) were started on and treated with insulin glargine or NPH insulin for 24-36 weeks. HbA1c and fasting blood glucose levels, percent achieving HbA1c target of <7% and insulin dose change were recorded.. For both men and women, HbA1c levels were significantly reduced over time (p < 0.001); a significantly greater HbA1c reduction was observed in men than in women (-1.36 vs. -1.22; p = 0.002). Significantly fewer women achieved target HbA1c of <7% (p < 0.001). At the study end, women had a significantly higher insulin dose/kg than men (0.47 vs. 0.42 U/kg; p < 0.001). The incidence rates of severe and severe nocturnal hypoglycaemia were significantly higher in women (3.28% vs. 1.85%; p < 0.05 and 2.24% vs. 0.59%; p < 0.001, respectively). Women were more likely to experience severe hypoglycaemia [odds ratio (OR) 1.80; 95% confidence interval (CI) 1.08, 3.00; p = 0.02] and severe nocturnal hypoglycaemia (OR: 3.80; 95% CI 1.72, 8.42; p = 0.001).. These observations confirm studies that found a smaller improvement in HbA1c and greater hypoglycaemia in women during insulin treatment. Physicians should be aware of the need to determine and closely monitor dosing, particularly in women, to optimize the balance between glycaemic control and hypoglycaemia risk.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Prevalence; Randomized Controlled Trials as Topic; Sex Factors; Treatment Outcome

To conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively.. The EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249).. No significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (≤3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with ≥1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low (<1 kg) in both groups, with less gain with Gla-300 [LS mean difference -0.28 kg (95% CI -0.55 to -0.01); p = 0.039]. Both treatments were well tolerated, with similar rates of adverse events.. Gla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Randomized Controlled Trials as Topic

The limitations of current basal insulin preparations include concerns related to their pharmacokinetic and pharmacodynamic properties, hypoglycaemia, weight gain, and perception of management complexity, including rigid dosing schedules. Insulin degludec (IDeg) is a novel basal insulin with improved pharmacokinetic and pharmacodynamic properties compared to insulin glargine (IGlar) including a long half-life of ∼25 h and a duration of action >42 h at steady state, providing a flat and stable blood glucose-lowering effect when injected once daily. Evidence from phase 3a clinical trials with a treat-to-target design in patients with type 1 and type 2 diabetes has shown that IDeg has similar efficacy to IGlar, with a 9% and 26% reduction in risk of overall and nocturnal hypoglycaemia, respectively (in the pooled population) during the entire treatment period, and a 16% and 32% reduction during the maintenance period, respectively. Given its pharmacodynamic properties, IDeg offers a broad dosing window, allowing for flexible dose administration, if required. Two different formulations of IDeg are available (100 units/mL [U100] and 200 units/mL), the latter providing the same IDeg dose as the U100 formulation in half the injection volume. The unique pharmacokinetic profile of IDeg facilitates glycaemic control while minimising the risk of nocturnal hypoglycaemia.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Weight Gain

Insulin glargine 100 units/ml (Gla-100) has become a standard of care in diabetes treatment over the past decade, providing 24-h basal insulin coverage after once-daily subcutaneous injection for many people with diabetes, with a well-established efficacy and safety profile. New insulin glargine 300 units/ml (Gla-300) is a basal insulin that provides the same number of units as Gla-100 in a third of the volume. Compared with Gla-100, Gla-300 has shown more constant and prolonged pharmacokinetic (PK)/pharmacodynamic (PD) profiles. This review summarizes the findings from the EDITION series of clinical trials that investigated Gla-300 in individuals with type 1 and type 2 diabetes mellitus. Overall, Gla-300 has been shown to achieve similar glycaemic control with less, or similar, nocturnal hypoglycaemia compared with Gla-100, and a trend towards lower hypoglycaemia at any time of day. The EDITION series of clinical trials also provides some evidence for less weight gain with Gla-300 than with Gla-100. In addition, the PK/PD profiles of Gla-300 may allow more flexibility in the timing of doses, improving convenience; thus, Gla-300 could offer several positive features for individuals with diabetes requiring basal insulin therapy.

Topics: Administration, Oral; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Compounding; Drug Therapy, Combination; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Randomized Controlled Trials as Topic; Weight Gain

Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar).. Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy.. This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Humans; Hypoglycemia; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

To describe the studies evaluating the efficacy and safety of new insulin glargine 300 U/mL (Gla-300) as a basal insulin in the treatment of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus.. A literature search of MEDLINE was conducted (January 2008-June 2015) using the terms U300, Gla-300, and insulin glargine 300 units/mL and supplemented with congress abstracts published in 2014 and 2015.. All English language studies assessing the efficacy and/or safety of Gla-300 were evaluated.. The efficacy and safety of once-daily Gla-300 has been compared with insulin glargine 100 U/mL (Gla-100) in the EDITION trials, 6 phase-3, multinational, open-label studies in T1DM and T2DM. Across these studies, Gla-300 consistently demonstrated glycemic control comparable to Gla-100; a mean (standard error) change in glycated hemoglobin A1c of -1.02% (0.03) with both Gla-100 (n = 1235) and Gla-300 (n = 1239) was seen in a patient-level meta-analysis. Gla-300 was associated with comparable or reduced nocturnal hypoglycemia compared with Gla-100; the relative risk for nocturnal hypoglycemia with Gla-300 versus Gla-100 was 0.75 (95% CI = 0.68 to 0.83) in a patient-level meta-analysis. There is also some evidence for less weight gain with Gla-300 compared with Gla-100, despite a higher insulin dose. Gla-300 was well tolerated, with the number of adverse events being comparable to that with Gla-100.. These results suggest that Gla-300 may have a place as an alternative, long-acting basal insulin for patients with T1DM or T2DM, with the possibility for improved tolerability.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

Treat-to-target trial designs compare investigational insulins with a standard insulin. Treat-to-target trials force-titrate insulin dosages to achieve a prespecified treatment goal. With comparable glycaemic control, comparisons of safety endpoints such as hypoglycaemia can be made to establish the risk-benefit profile of the new insulin. Glargine versus NPH showed comparable A1C reductions; however, A1C <7% without associated nocturnal hypoglycaemia was reached in more patients on glargine and overall hypoglycaemia was lower. Detemir versus glargine showed non-inferiority between the groups; however, with less weight gain and more injection site reactions with detemir. Detemir/aspart versus glargine/aspart showed non-inferiority between the treatments, however, with less weight gain in the detemir group but comparable risk of hypoglycaemia. Degludec in combination with aspart versus glargine/aspart showed comparable A1C reductions. However, degludec-treated patients had less overall hypoglycaemia and less nocturnal hypoglycaemia. Because insulin titrations are guided by goal attainment with each treatment, treat-to-target trials enable clinicians to determine differences in non-glycaemic treatment effects, such as rates of hypoglycaemia and weight gain, at the same level of glycaemic control.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome

To assess patient-reported outcomes associated with initiating insulin glargine among insulin-naïve patients with type 2 diabetes mellitus (T2DM).. This was a pooled analysis of patient-level data from Phase 3, randomized controlled trials evaluating once-daily insulin glargine vs. comparator treatment for ≥24 weeks in previously insulin-naïve adult patients with T2DM and poor glycaemic control. Eligible studies utilized strict, predefined insulin titration algorithms with weekly dose-adjustment to achieve fasting plasma glucose (FPG) levels of ≤5.6 mmol/l. Treatment satisfaction was measured using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) change (c) and status (s) versions.. A total of 1577 patients from four studies were included; 830 patients treated with insulin glargine and 747 with comparators. At week 24, DTSQc scores improved in both groups with a significantly higher increase in treatment satisfaction for insulin glargine vs. comparators (13.5 vs. 12.1; p < 0.0001). Multivariate regression analysis revealed that significant predictors of DTSQc improvement at week 24 were insulin glargine treatment (p < 0.0001), higher baseline DTSQs (p < 0.0001), and lower baseline body weight (p = 0.0103). Greater improvement in DTSQc at week 24 was significantly associated with decrease from baseline in glycosylated haemoglobin (p < 0.001) and FPG (p = 0.0001); a numerically more positive change in weight from baseline approached significance (p = 0.07).. Initiation of insulin glargine in insulin-naïve patients with T2DM is associated with greater improvements in treatment satisfaction than alternative interventions, with perceived improvements in glycaemic control and baseline weight likely to be important factors.

Topics: Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Endpoint Determination; Fasting; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Time Factors; Treatment Outcome

This meta-analysis of 5 trials from the Phase 3a insulin degludec (IDeg) clinical trial program evaluated the risk of hypoglycemia in a subset of subjects with type 2 diabetes (T2D) who required high basal insulin doses at the end of the trials.. This meta-analysis compared glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), basal insulin dose, body weight, and rates of overall and nocturnal confirmed hypoglycemia in a pooled population of T2D subjects using >60 U basal insulin at trial completion. Five Phase 3a, open-label, randomized, treat-to-target, confirmatory 26- or 52-week trials with IDeg (n = 2,262) versus insulin glargine (IGlar) (n = 1,110) administered once daily were included. Overall confirmed hypoglycemia was defined as self-measured blood glucose >56 mg/dL or any episode requiring assistance; nocturnal confirmed hypoglycemia had an onset between 00:01 and 05:59 AM.. More than one-third of IDeg- (35%) and IGlar- (34%) treated T2D subjects required >60 U of basal insulin daily at the ends of the trial. Patients achieved similar mean HbA1c values (estimated treatment difference [ETD] IDeg - IGlar: 0.05%, P = .44) while mean FPG values were lower with IDeg than IGlar (ETD: -5.9 mg/dL, P = .04) at end-of-trial. There was a 21% lower rate of overall confirmed hypoglycemic episodes for IDeg (estimated rate ratio [RR] IDeg/IGlar: 0.79, P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes for IDeg (RR: 0.48, P<.01).. In this post hoc meta-analysis, more than 30% of subjects with T2D required >60 U/day of basal insulin at the end of the trials. In these individuals, IDeg achieves similar HbA1c reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Risk

The aim of this analysis was to evaluate the cost-effectiveness of insulin degludec (IDeg) versus insulin glargine (IGlar) in adults with type 2 diabetes mellitus (T2DM) who are considered appropriate for treatment with a basal insulin analogue, using a short-term economic model.. Meta-analysis data from three phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg versus IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results.. IDeg is a cost-effective treatment option versus IGlar in patients with T2DM using basal insulin. Base case incremental cost-effectiveness ratios (ICERs) were estimated at £15,795 per quality-adjusted life-year (QALY) and £13,078 per QALY, which are below commonly accepted thresholds for cost-effectiveness. Sensitivity analyses demonstrated that hypoglycaemia event rates had an important effect on the results. With higher event rates for non-severe hypoglycaemia IDeg was less costly and more effective than IGlar (dominant). Conversely, using lower event rates for severe hypoglycaemia generated higher ICERs. Using hypoglycaemia rates from a subgroup of patients who experienced ≥1 hypoglycaemic event per year IDeg was highly cost-effective versus IGlar; with estimated ICERS of £4887 and £2625 per QALY.. This short-term modelling approach allows the economic evaluation of newer insulin analogues when advanced long-term modelling based on HbA1c differences is inappropriate. For patients with T2DM who are considered appropriate for treatment with a basal insulin analogue, IDeg is a cost-effective treatment option compared with IGlar and offers additional benefits to subgroups of patients, such as those suffering from recurrent hypoglycaemia.

Topics: Adult; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Models, Economic; National Health Programs; Quality-Adjusted Life Years; Treatment Outcome; United Kingdom

It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar).. The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI).. Five trials, including a total number of 1758 patients followed up from 24 to 28 weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3 RCTs; WMD (95% CI): -14.70 mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09 mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR = 1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI) = 0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI) = 1.78 kg (1.04; 2.52)].. BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk of severe hypoglycaemic episodes.

Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain

The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success. The subsequent elucidation of the chemical and three-dimensional structure of insulin and its chemical synthesis and biosynthesis allowed modification of the insulin molecule itself, resulting in insulin analogs that are designed to mimic normal endogenous insulin secretion during both fasting and prandial conditions. Insulin glargine was the first once-daily, long-acting insulin analog to be introduced into clinical practice more than 10 years ago and is specifically designed to provide basal insulin requirements. It has a prolonged duration of action and no distinct insulin peak, making it suitable for once-daily administration and reducing the risk of nocturnal hypoglycemia that is seen with intermediate-acting insulins. Insulin glargine can be used in combination with prandial insulin preparations and non-insulin anti-diabetic agents according to individual requirements.

Topics: Animals; Delayed-Action Preparations; Diabetes Mellitus; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Time Factors

Evaluate early (0-12 weeks) and later (12-24 weeks) treatment outcomes in subjects with type 2 diabetes not achieving glycaemic control with oral antidiabetes drugs (OADs).. Selected data were pooled from 15 randomised, controlled treat-to-target (fasting plasma glucose < 100mg/dL [< 5.6 mmol/L]) trials adding insulin glargine to metformin, a sulphonylurea, or both. Glycaemic and hypoglycaemia parameters, insulin dose, and body weight at weeks 12 and 24 were assessed using individualised subject-level data.. Data from 2837 subjects were analysed. HbA1c decreased from 8.8% (73 mmol/mol) at baseline by 1.4% (15 mmol/mol) at Week 12, and a further 0.2% (2 mmol/mol) at Week 24 in the pooled population. Similar reductions were observed across the different treatment groups. HbA1c < 7.0% (<53 mmol/mol) was reached by 34.8% of participants at Week 12 and an additional 24.3% by Week 24. Hypoglycaemia incidence and rates were similar during the early and continued treatment periods across all treatment combinations, but were markedly lower for insulin glargine plus metformin versus the other 2 regimens.. Early and sustained glycaemic benefits with a low-risk of hypoglycaemia are observed after initiation of insulin glargine in a pooled type 2 diabetes cohort previously uncontrolled on OADs.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Treatment Outcome

GLP-1 receptors agonists have been a substantial change in treatment of type 2 diabetes mellitus, and its weekly administration has broken pre-established schemes. Daily exenatide is administered every 12 hours (BID) subcutaneously, while weekly exenatide is administered once a week. Both molecules share a common mechanism of action but have differential effects on basal and postprandial glucose. We review the major clinical trials with both exenatide BID and weekly exenatide. It can be concluded that exenatide BID shows a hypoglycemic effect similar to other treatments for type 2 DM but adding significant weight loss with low incidence of hypoglycemia. Weekly exenatide decreases HbA1c similar to liraglutide but larger than exenatide BID, both glargine and biphasic insulin, sitagliptin, and pioglitazone, maintaining weight loss and adding to gastrointestinal intolerance the induration at the injection site as a side effect.

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Exenatide; Female; Gastrointestinal Diseases; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Metformin; Peptides; Pioglitazone; Receptors, Glucagon; Thiazolidinediones; Venoms; Weight Loss

To determine whether baseline characteristics, especially haemoglobin A1c (HbA1c), predict the likelihood of reaching HbA1c ≤ 7.0% or the risk of experiencing hypoglycaemia after the addition of insulin glargine to oral therapy in type 2 diabetes.. Pooled patient-level data from 12 prospective, randomized, controlled studies that used insulin glargine in a treat-to-target titration regimen seeking fasting glucose levels ≤5.5 mmol/l (100 mg/dl) were analysed. Baseline characteristics were evaluated by logistic regression models as predictors of reaching a target HbA1c ≤ 7.0% or experiencing confirmed hypoglycaemia. The effect of prior glycaemic control was further explored by analysis of categorical ranges of baseline HbA1c.. Of 2312 participants, 95% completed 24 weeks of treatment. Lower HbA1c at baseline was independently associated with reaching HbA1c target [adjusted odds ratio (OR) for 1% difference: 0.538, p < 0.0001] and also with likelihood of experiencing confirmed hypoglycaemic events (adjusted OR: 0.835, p < 0.0001) at week 24. In an unadjusted analysis by baseline HbA1c range, the strong association between baseline control and attaining target HbA1c was confirmed (75% with baseline HbA1c < 8.0%, 60% with baseline HbA1c ≥ 8.0 and <9.0% and 38% with baseline HbA1c ≥ 9.0% attained HbA1c ≤ 7.0%). The incidence of hypoglycaemia confirmed <3.9 mmol/l (70 mg/dl) was higher in the lower baseline HbA1c ranges but severe hypoglycaemia was infrequent at all baseline HbA1c levels.. Systematically titrated insulin glargine, added to oral agents, was effective over a wide range of baseline HbA1c. Lower baseline HbA1c was the best clinical predictor of achieving HbA1c ≤ 7.0% and also associated with higher risk of glucose-confirmed hypoglycaemia. Severe hypoglycaemia was infrequent using this treatment approach.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Risk Assessment; Treatment Outcome

Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes. The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy. Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycaemic control in women with type 1 diabetes. However, a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short-acting analogue where the woman's diabetes is well controlled with human insulin. There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended. Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes. There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control. A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia. The greater evidence base supports the use of insulin detemir as the first line long-acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin. There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Randomized Controlled Trials as Topic; Treatment Outcome

To compare the impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin glargine or NPH insulin.. A pooled analysis of 24-week patient level data from randomized controlled studies comparing once-daily insulin glargine with once-daily NPH insulin in insulin-naïve adult patients with T2DM was performed, stratifying patients into quartiles by duration of diabetes: <5.8 years; 5.8 to <9.2 years; 9.2 to <14 years and ≥14 years. Daytime and nocturnal hypoglycaemia events were evaluated.. Data from 2330 patients in four randomized controlled trials were included in the analysis; 1258 treated with insulin glargine and 1072 with NPH insulin. The rates of daytime hypoglycaemia were similar for insulin glargine and NPH insulin, irrespective of disease duration. Patients with longer T2DM duration treated with glargine experienced greater glycated haemoglobin A1c (HbA1c) reductions. Rates of severe nocturnal hypoglycaemia and nocturnal hypoglycaemia [self-monitored blood glucose < 70 mg/dl (3.89 mmol/l) and < 50 mg/dl (2.78 mmol/l)] were all significantly and positively correlated with the duration of diabetes for patients treated with NPH insulin but not with insulin glargine. Despite improvements in HbA1c, rates of symptomatic nocturnal hypoglycaemia were significantly lower with insulin glargine than with NPH insulin in patients with longer T2DM duration.. There is a lower risk for nocturnal hypoglycaemia with insulin glargine than with NPH insulin. When considering diabetes duration, insulin glargine (compared to NPH insulin) may be particularly beneficial in patients with a longer duration of T2DM.

Topics: Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Time Factors

Primary care practitioners are increasingly responsible for the management of the escalating numbers of patients with type 2 diabetes. The majority of these patients will require insulin replacement therapy as their disease progresses, because glycemic control is often unsustainable using oral antidiabetic drugs. This review explains the practicalities of initiating and optimizing basal insulin in clinical practice, emphasizing the need for regular glycated hemoglobin (A1c) monitoring to allow timely initiation of insulin when the A1c target is not met. The importance of patient education in overcoming barriers to insulin is discussed, as well as the choice of available basal insulins and the necessity to optimize basal insulin dosage by self-titration. The traditional view of insulin therapy as a last resort is challenged with the modern basal insulin analogues (insulin detemir and insulin glargine), which offer simple and effective glycemic control with a reduced risk of hypoglycemia compared with older insulin formulations such as neutral protamine Hagedorn.

Topics: Decision Making; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Patient Education as Topic; Primary Health Care

Elderly patients with diabetes are more vulnerable to the occurrence and effects of hypoglycaemia; therefore, treatments with low risk of hypoglycaemia are preferred in this population. This study aimed to compare hypoglycaemia rates between insulin degludec (IDeg) and insulin glargine (IGlar) in elderly patients.. Hypoglycaemia data from patients ≥65 years of age with type 1 (T1DM) or type 2 (T2DM) diabetes from seven randomised, treat-to-target phase IIIa trials were used to compare IDeg and IGlar in a pre-planned meta-analysis. Overall, 917/4345 (21 %) randomised patients in the seven trials were elderly (634 IDeg, 283 IGlar). Overall confirmed hypoglycaemia was defined as <3.1 mmol/L or severe hypoglycaemia (symptoms requiring external assistance). Nocturnal hypoglycaemia included confirmed episodes from 0001 to 0559 hours (inclusive). Treatment comparisons of hypoglycaemia in T1DM patients were not performed due to low numbers of elderly patients with T1DM randomised (43 IDeg, 18 IGlar); statistical comparisons were also not made for severe hypoglycaemia due to the low number of events.. In elderly patients with T2DM, the rate of overall confirmed hypoglycaemia was significantly lower with IDeg than IGlar [estimated rate ratio (ERR) 0.76 (0.61; 0.95)95 % CI]; nocturnal confirmed hypoglycaemia was also significantly lower with IDeg [ERR 0.64 (0.43; 0.95)95 % CI]. Confirmed hypoglycaemia occurred in the majority of T1DM patients, whereas severe episodes occurred infrequently and at similar rates in both treatment groups in T1DM and T2DM.. Results of this pre-planned meta-analysis in elderly patients with diabetes demonstrate a significant reduction in hypoglycaemic events with IDeg relative to IGlar.

Topics: Aged; Aged, 80 and over; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Weight Gain

Degludec is a novel long-acting insulin analogue, providing an adequate supply of basal insulin over 24 hours with one daily injection, with a supposed greater reproducibility and flexibility than other basal insulins.. An extensive search of Medline and the Cochrane Library for 'degludec' was performed, up to July 1st, 2012, collecting all randomised trials with a duration of at least 16 weeks and enrolling patients with diabetes. The principal outcome was the effect of degludec, compared with other basal insulins, on endpoint HbA1c and hypoglycaemia. Secondary outcomes included BMI, FPG at endpoint, and the incidence of cardiovascular events and cancer.. In the four trials comparing degludec with glargine, endpoint HbA1c was similar in the two groups, whereas FPG was significantly lower in degludec-treated patients. Degludec was associated with a lower rate of overall and nocturnal hypoglycaemia in type 2 and type 1 diabetes, respectively. No differences were observed for cardiovascular events and cancer.. The number of available trials and the duration of exposure were limited, so the results obtained should be considered preliminary.. Degludec appears to be associated with a lower incidence of hypoglycaemia in comparison with glargine, for similar levels of glycaemic control. The use of this agent could represent one step further in insulin therapy.

Topics: Blood Glucose; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

We aimed to determine risk factors associated with hypoglycemia during subcutaneous insulin therapy in non-critically ill patients with type 2 diabetes.. We conducted an analysis of three randomized control trials using basal/bolus regimen and regular sliding scale insulin (SSI) in patients with diabetes admitted to medical and surgical settings.. We analyzed medical records of 261 general medicine and 211 noncardiac surgery patients treated with basal/bolus regimen with glargine/glulisine (n = 169), detemir/aspart (n = 67), neutral protamine Hagedorn/regular (n = 63), or with SSI (n = 173). The overall frequency of mild and severe hypoglycemia (<70 and <40 mg/dl) was 19% and 2%, respectively. During treatment, medical patients experienced a higher number of hypoglycemia than surgical patients (23% versus 13%; p = .005), but the rate of severe hypoglycemia was similar between groups (1.9% versus 1.9%; p = not significant). Increasing age, impaired kidney function (glomerular filtration rate < 60 ml/min), total daily insulin dose, and type of insulin regimen (basal/bolus versus SSI) during hospitalization were important contributors for hypoglycemia in both medical and surgical patients. Among these variables, increasing age and type of insulin regimen (basal/bolus versus SSI) were found to be independent predictors of hypoglycemic events.. Mild hypoglycemic events are common during subcutaneous insulin therapy in medical and surgical patients with type 2 diabetes. Increasing age, impaired renal function, daily insulin dose, and insulin regimen (basal/bolus versus SSI) are important predictors of hypoglycemia during insulin therapy in patients with type 2 diabetes mellitus.

Topics: Aged; Critical Illness; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Subcutaneous; Inpatients; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

To evaluate the benefits of initiating insulin at an earlier versus later treatment stage, and regimens with/without sulfonylurea (SU).. Pooled analysis of 11 prospective randomized clinical trials, including 2171 adults with uncontrolled type 2 diabetes initiating insulin glargine following a specific titration algorithm. Clinical outcomes were glycated haemoglobin A1c (HbA1c) reduction, per cent achieving HbA1c ≤ 7.0%, weight gain and hypoglycaemic events. Statistical analysis compared outcomes 24 weeks after basal insulin initiation in patients previously uncontrolled on 0/1 oral antidiabetic drug (OAD) versus 2 OADs, and in patients taking metformin (MET) or SU alone or in combination at baseline. A meta-analysis was also conducted.. For the pooled analysis, patients on 0/1 OAD and those on MET monotherapy at baseline had the largest 24-week reductions in HbA1c following the addition of insulin glargine (∼0.44 U/kg). Of patients failing MET/SU monotherapy and MET + SU in combination, 68.1, 50.4 and 56.4% achieved HbA1c ≤ 7.0%, respectively (p = 0.0006). Weight gain was lowest when basal insulin was added to MET. Patients on 0/1 OAD at baseline had significantly less symptomatic hypoglycaemia when basal insulin was added than those on 2 OADs (p = 0.0007). Despite higher insulin doses, those taking MET alone had less hypoglycaemia than those taking SU or MET + SU. Results were confirmed in the meta-analysis.. Adding insulin glargine to MET monotherapy early in treatment may provide efficacy/safety benefits over regimens including SU. This may reflect treatment earlier in the disease and supports the inclusion of insulin as a second step in the American Diabetes Association/European Association for the Study of Diabetes treatment algorithm.

Topics: Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Treatment Outcome

As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks and HbA1c ≤ 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c ≤ 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Off-Label Use; Pregnancy; Pregnancy in Diabetics

Topics: Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Gliclazide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Risk Factors

Basal insulin analogues are an effective treatment for type 2 diabetes with proven efficacy, and insulins NPH, detemir and glargine have shown comparable glycaemic control. However, pharmacokinetics and clinical studies highlight the advantages of insulins detemir and glargine over insulin NPH in terms of once-daily dosing, reduced risk of hypoglycaemia, reduced within-patient variability, appropriate duration of action and simple titration. Insulin detemir has demonstrated the additional advantage of less weight gain. Introduction of insulin detemir, at the appropriate time, can help empower patients to reach glycaemic targets, with a reduced risk of hypoglycaemia and less weight gain.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

The widespread use of insulin analogues is based not only on the pharmacokinetics of these preparations, which is much closer to the physiology of insulin secretion under normal conditions, but also on their safety and effectiveness. The publication of a possible association between the use of a long-acting insulin analogue (glargine) and breast cancer has caused uneasiness among the medical community regarding the safety of these analogues. The mechanism of increased tumor activity of insulin analogues is explained by the fact that they act through insulin receptors (IR) and insulin-like growth factor-1 (IGF-1R), stimulating cell growth and inhibiting apoptosis. There are two major mechanisms: an increase in the binding time of insulin to IR and increased activation of IGF-1R. Therefore, to evaluate the safety of an analogue, the slower dissociation rate from its insulin receptor must be excluded, as well as the increased affinity for the IGF-1 receptor. This is equivalent to an index of mitogenic/metabolic activity of less than 1. These aspects can only be evaluated through study of cell lines and animal testing, which are reductionist models that cannot always be extrapolated to humans. To date, there are no data to question the safety of insulin analogues in general. However, the results of observational studies and some in vitro studies, suggesting a potential risk of mitogenicity with the administration of glargine, have caused some alarm among the medical community. Until now, there are no data to refute or confirm this risk and, therefore, evaluation of the existing data is crucial to obtain objective information.

Topics: Amino Acid Sequence; Animals; Apoptosis; Cell Line, Tumor; Cell Transformation, Neoplastic; Diabetes Mellitus; Drug Evaluation, Preclinical; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Long-Acting; Male; Mammary Neoplasms, Experimental; Mitosis; Molecular Sequence Data; Neoplasms; Rats; Rats, Sprague-Dawley; Receptor, IGF Type 1; Receptor, Insulin

Most guidelines suggest that failure of oral antidiabetic drugs should be followed by the addition of a basal insulin with aggressive titration of the dose. In most countries, neutral protamine Hagedorn (NPH)-insulin, glargine and detemir are the only choices. Clinical trials show that the metabolism and metabolic outcomes after treatment with intermediate- or long-acting insulins differ little. Despite this, the hypoglycaemic potential, effect on body weight and adherence to insulin treatment may affect the choice of basal insulin. Adherence seems to be negatively correlated to the prescribed dose and the number of injections. Furthermore, the choice of basal insulin might be influenced by the number of units necessary to achieve the goal for HbA1c.. By searching the literature systematically, we identified all randomised clinical trials comparing long-acting insulins (human NPH-insulin and the analogues glargine and detemir) for the treatment of type 2 diabetes conducted over the last 10 years. We continued by reviewing only studies in which similar antihyperglycaemic potential of the treatments was achieved.. According to the inclusion criteria for this review, all drugs were efficacious regarding the main purpose of decreasing glycaemia. For an equal efficacy, we were able to detect other differences between the treatments and, furthermore, an estimate on the number of units of insulin needed to achieve comparable glycaemic control.. The analysis confirmed a favourable profile of both analogues regarding hypoglycaemia. For detemir, we additionally identified a favourable profile regarding weight gain and need for an increased number of units of insulin to achieve comparable glycosylated haemoglobin (HbA1c) responses. We conclude that the efficacy of insulin treatment seems to vary little between the available products, however doses needed to achieve similar effects vary; units used per HbA1c reduction could be a relevant parameter for the choice of insulin.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Time Factors; Treatment Outcome; Weight Gain

To estimate absolute and relative incidence rates of hypoglycaemia when using once-daily evening or morning regimens of insulin glargine (glargine) versus once-daily evening NPH insulin (NPH) using individual patient data (IPD).. Randomized controlled trials with accessible IPD and including white European people with type 2 diabetes (T2DM) using glargine or NPH once-daily (with oral glucose-lowering drugs) were identified. Two study pools were analysed: evening glargine versus evening NPH (pool 1); and morning glargine versus evening NPH (pool 2). The number-needed-to-treat to avoid hypoglycaemia was calculated for glargine versus NPH.. In study pool 1 (n = 2711), the risk of nocturnal hypoglycaemia was approximately halved with glargine compared with NPH [odds ratios (OR): 0.44-0.52, p < 0.001-0.047]. This led to a significant reduction in anytime risk of symptomatic hypoglycaemia [plasma glucose (PG) <3.9 mmol/l, OR: 0.64, p = 0.018; PG <2.0 mmol/l, OR: 0.51, p < 0.001]. In study pool 2 (n = 470), although a strong numerical reduction in all types of nocturnal hypoglycaemia was observed (OR: 0.16-0.64), statistical significance was reached only for symptomatic hypoglycaemia with PG <3.9 mmol/l (p < 0.001). Eight (pool 1) or five (pool 2) people with T2DM needed to use glargine rather than NPH to avoid one person from experiencing a nocturnal symptomatic hypoglycaemic event within a median of about 25 weeks of starting insulin.. This meta-analysis of open-label studies provides confidence that reductions of around 50% of risk for nocturnal hypoglycaemia can be achieved with using glargine instead of NPH.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

The natural progression of type 2 diabetes mellitus (T2DM) requires continuing medical care, early insulin intensification and patient self-management education to reduce the risk of long-term complications, including microvascular and macrovascular complications. However, too few people are on insulin, and all too commonly have poor glycaemic control. This paradigm significantly increases the risk for long-term complications. It is becoming increasingly apparent that the early introduction of basal insulin, such as insulin glargine, is essential to provide clinically important improvements in glycaemic control. In this review, we discuss the rationale for the earlier insulinization in T2DM in order to reach and maintain treatment targets and to provide further support for the recent American Diabetes Association and European Association for the Study of Diabetes consensus statement.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Insulin therapy is often essential in people with type 2 diabetes mellitus (T2DM) but is typically not initiated early enough or aggressive enough, leading to worsening of glycaemic control and the majority of people staying above recommended haemoglobin A(1c) (HbA(1c)) targets of <7%. The extensive clinical experience gained with insulin glargine, in particular, the low risk of hypoglycaemia and consistent improvements in HbA(1c), suggests that insulin glargine can be initiated aggressively to help patients reach such HbA(1c) targets. However, many clinicians may be unaware of how easy it is to initiate insulin glargine. Indeed, the once-daily injection of insulin glargine plus once-daily measurement of blood glucose should provide little difficulty for patients. In the current review, the options for the initiation of insulin glargine in T2DM and how the patient can become more involved in management of their diabetes are discussed. The advantages of insulin glargine in randomized controlled trials and how these have translated into everyday clinical practice are also discussed.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Patient Education as Topic; Power, Psychological; Randomized Controlled Trials as Topic; Titrimetry

Within the USA, between 1980 and 2005, the prevalence of diagnosed diabetes has increased in all age groups, with the age group 65-74 years having the highest prevalence. The treatment of type 2 diabetes mellitus (T2DM) in elderly people is made more difficult than in their younger counterparts, primarily owing to the impact of co-morbidities, complications and hypoglycaemia as well as technical difficulties with insulin injections. Accordingly, the treatment approach for elderly patients with T2DM may need to be modified to accommodate co-morbidities and illnesses associated with ageing. Risks associated with insulin therapy, particularly hypoglycaemia, have traditionally limited the use of insulin in this patient population. Insulin glargine is associated with a low risk of hypoglycaemia compared with neutral protamine Hagedorn insulin, for example, and could thus provide a treatment of choice for healthcare providers when considering the increasing prevalence of diabetes in the elderly population. A regimen based on insulin glargine plus oral agents provides clinicians with a tool to help meet therapeutic targets in this population without increasing risk of hypoglycaemia.

Topics: Aged; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Basal insulin administered to type-2 diabetic patients with poor glycaemic control when managed with oral anti-diabetics (OADs) alone can lead to an increased risk of weight gain and hypoglycaemia. In the absence of head-to-head trials, an indirect comparison of the once-daily insulin detemir with insulin glargine was conducted on the following outcomes: weight gain, hypoglycaemic episodes, and HbA(1c).. Parallel-group randomised controlled trials of at least 20 weeks duration that compared once-daily evening glargine or detemir with a common comparator, neutral protamine Hagedorn insulin (evening), were selected. Trials focused on insulin-naïve, type-2 diabetic patients poorly controlled with OAD. Five open-label trials were identified (n = 2,092 patients; n = 1 detemir and n = 4 glargine trials), with an indirect comparison of glargine (n = 869 patients) and detemir trials (n = 169 patients) carried out using meta-regression to control for covariates. Weight gain was analysed as weighted mean differences (WMD), hypoglycaemic episodes as odds ratios (OR), and HbA(1c) at the end of study as standardised mean differences (SMD).. Patients receiving evening detemir gained significantly less weight (unadjusted WMD -1.22 kg, 95% CI -2.15, -0.29 kg; p = 0.010) and significantly fewer of them experienced hypoglycaemic episodes versus evening glargine (unadjusted OR 0.52, 95% CI 0.28, 0.98; p = 0.044). There was no significant difference between treatments for the mean HbA(1c) level at study endpoint (unadjusted SMD 0.09, 95% CI -0.16, 0.33; p = 0.480).. Once-daily use of insulin detemir resulted in significantly less weight gain and fewer hypoglycaemic episodes than glargine, while maintaining clinically appropriate HbA(1c) levels in type-2 diabetic patients currently receiving OAD.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Regression Analysis; Weight Gain

Insulin glargine (Lantus) was the first recombinant-DNA long-acting insulin analogue to be licensed for use in the treatment of diabetes mellitus.. This review considers the use of insulin glargine in the treatment of type 2 diabetes (T2DM).. Medline, Cochrane and Embase databases were searched for relevant papers from the year 2000 onwards.. Overall glargine provides at least equivalent glycaemic control and is associated with less hypoglycaemia, especially nocturnal hypoglycaemia owing to its 24 h peakless profile, which allows more aggressive titration to achieve glycaemic targets. Glargine has been shown to be safely initiated both individually and within a group setting and titration algorithms self-managed by patients are effective in achieving diabetes control. Despite these advantages, caution is needed as clinical guidelines do not advocate its use in all people with T2DM until clinical efficacy and cost effectiveness have been proved. However, insulin glargine is a welcome addition to the plethora of treatment options available for T2DM.

Topics: Algorithms; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

The insulin treatment in type 2 diabetes mellitus (DM 2) is an explosive subject within health economics. This article discusses the significance of treating DM 2 patients with long-acting insulin analogues. Several studies have shown that the therapy with insulin glargine ist associated with a markedly lower rate of hypoglycaemia compared to NPH insulin. As the improvement of HbA1c is accompanied by a higher risk for hypoglycaemia, this goal is accomplished more effectively and safely with long acting insulin analogues.

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Prognosis; Risk Factors

We systematically analysed evidence from randomized controlled trials (RCTs) examining the safety and efficacy of neutral protamine Hagedorn (NPH) insulin and glargine in the management of adults with Type 2 diabetes.. Studies were identified by searching medline (1966-March 2007), embase (1974-2007), American Diabetes Association abstract database and the Cochrane Central Register of Controlled Trials using Medical Subject Headings (MeSH) diabetes mellitus, Type 2, insulin, insulin isophane, hypoglycaemic agents and the keywords glargine and NPH. Data on study design, participants, fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), body weight and hypoglycaemia were independently abstracted by two investigators using a standardized protocol.. Data from a total of 4385 participants in 12 RCTs were pooled using a random-effects model. The mean net change (95% confidence interval) for FPG, HbA(1c) and body weight for patients treated with NPH insulin as compared with glargine was 0.21 mmol/l (-0.02 to 0.45), 0.08% (-0.04 to 0.21) and -0.33 kg (-0.61 to -0.06), respectively, with negative values favouring NPH and positive values favouring glargine. More participants experienced symptomatic and nocturnal hypoglycaemia on NPH than glargine, but there was no significant difference in confirmed or severe episodes.. We identified no difference in glucose-lowering between insulin glargine and NPH insulin, but less patient-reported hypoglycaemia with glargine and slightly less weight gain with NPH in adults with Type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Statistics as Topic; Weight Gain

A recent meta-analysis evaluated trials of the rapid-acting analogues insulin lispro and insulin aspart, performed before the introduction of the basal analogues, insulin glargine and insulin detemir. This article reviews the effect of rapid-acting and basal insulin analogues separately and in combination, relative to human insulin. Outcomes evaluated include HbA(1c), hypoglycaemia, postprandial glucose (PPG), and weight changes. Results from trials that matched defined criteria are presented in tables. In type 1 diabetes, compared with human insulin, the rapid-acting analogues generally reduced hypoglycaemia and postprandial glucose, whereas the basal analogues tended to reduce hypoglycaemia -- particularly nocturnal hypoglycaemia. Weight gain may also be reduced with basal analogues, compared with human basal insulin. In type 2 diabetes, premix rapid-acting analogues controlled postprandial glucose better than human insulin mixes; basal analogues used as basal-only therapy reduced hypoglycaemia compared with NPH insulin; and some advantages were apparent with analogues in basal-bolus therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapid-acting analogues and the potential for reduction in cardiovascular risk, should be investigated further.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period; Randomized Controlled Trials as Topic

This analysis first modeled the interaction between hypoglycemia and glycosylated hemoglobin (HbA1c) in clinical trials that compared insulin glargine (glargine) with human neutral protamine Hagedorn insulin (NPH) in patients with type 1 or type 2 diabetes mellitus. The model was then used to compare rates of hypoglycemia associated with use of these insulins.. Patient-level data from all randomized Phase III/IV clinical trials sponsored by the manufacturer of glargine that compared glargine and NPH and were available in May 2004 were included in the model. In addition, MEDLINE, EMBASE, and BIOSIS were searched for comparative randomized controlled trials of glargine and NPH using the terms insulin glargine, HOE 901, neutral protamine Hagedorn insulin, and NPH insulin. Studies were excluded from the analysis if patient-level data were not available. Unadjusted rates of symptomatic, confirmed, and severe hypoglycemia were compared with those derived from negative binomial regression analysis, which stratified the results by HbA1c at end point (with last observation carried forward), treatment, and duration of diabetes. In addition, the analysis was stratified by Phase III studies (which focused on determining tolerability and efficacy before regulatory approval) and Phase IV studies (which compared the clinical efficacy of the 2 insulins). The first month of the study was not included in the analysis because of continual adjustment of the insulin dose and maintenance of previous NPH in some studies.. Eleven sponsored randomized trials were included in the model (total of 5074 patients). Four other sponsored trials were not included because the databases were not finalized, and 3 investigator-initiated trials were not included because patient-level data were unavailable. Rates of hypoglycemia had a curvilinear relationship with HbAlc, increasing at lower end-point HbAlc values. In combined analyses of the studies of type 1 and type 2 diabetes, unadjusted rates of hypoglycemia were lower for glargine than NPH: 6.1% lower for all symptomatic hypoglycemia, 21.6% lower for confirmed hypoglycemia, and 23.9% lower for severe hypoglycemia (all, P < 0.05). When modeled using the negative binomial distribution with end-point HbA1c as a covariate, the corresponding results were 9.1% (P < 0.05), 26.6% (P < 0.001), and 30.0% (P = 0.08), respectively. When only Phase IV trials were analyzed, the relative reductions with glargine were 16.2% (P < 0.01), 40.8% (P < 0.01), and 46.8% (P < 0.05). The results of the separate analyses of studies of type 1 and type 2 diabetes were comparable.. Based on the results of this analysis, calculated unadjusted hypoglycemia event rates appear to underestimate the differences between glargine and NPH. In most of the present analyses, unadjusted rates were significantly lower with glargine than NPH. Adjustment for end-point HbA1c resulted in greater relative reductions in the risk of hypoglycemia for glargine compared with NPH. The adjusted risk reduction with glargine was highest in the Phase IV studies.

Topics: Binomial Distribution; Blood Glucose; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Models, Statistical; Randomized Controlled Trials as Topic; Treatment Outcome

Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.. This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.. A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA(1c)], hypoglycemia, preprandial and postprandial blood glucose).. Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.. The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.

Topics: Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic

For both type 1 and type 2 diabetes, tight glycaemic control is vital to reduce the risk of long-term complications. However, this must be achieved with minimal risk of hypoglycaemia. Glargine is a new long-acting insulin analogue with an action profile designed to overcome this and has now been in clinical use for a number of years. In many countries glargine is widely used. Here we present an update on the clinical information available on glargine with respect to glycaemic control, the risk of hypoglycaemia and quality of life in both type 1 and type 2 diabetes.

Topics: Blood Glucose; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Quality of Life; Randomized Controlled Trials as Topic

Achieving and maintaining glycemic control (glycated hemoglobin--HbA(1c)< or =7.0% according to American Diabetes Association and < or =6.5% according to International Diabetes Federation) is the primary goal in treating diabetes, which lowers the risk for diabetes-related complications. Insulin therapy is essential for type 1 diabetes treatment. Insulin therapy in type 2 diabetes is initiated when glycemic control is inadequate despite the combination of antihyperglycemic drugs. The type of insulin therapy is selected according to the patient's lifestyle and needs. Multiple insulin injection therapy and premixed insulin therapy are usually administered. In multiple insulin injection therapy, basal insulin is administered one or two times a day, and regular human insulin or rapid-acting insulin analog is administered with each meal. The duration of action of regular insulin is 6-8 hours; therefore, the risk for postprandial hypoglycemia is increased. The action of novel insulin analogs (rapid- and long-acting) closely mimics physiological insulin secretion. Three rapid-acting insulin analogs are currently available: insulin lispro, insulin aspart, and insulin glulisine. Insulin glulisine is the most recently approved rapid-acting insulin analog. It is safe, flexible, and effective in achieving target postprandial glycemic control. Moreover, the pharmacokinetics of insulin glulisine does not depend on the amount of subcutaneous fat. Basal insulins include intermediate-acting human insulins (neutral protamine Hagedorn) and long-acting insulin analogs (insulin glargine, insulin detemir). The latter are the optimal choice covering basal insulin requirement. Compared to neutral protamine Hagedorn insulin, long-acting insulin analogs have no pronounced concentration peak and reduce nocturnal hypoglycemia risk and weight gain.

Topics: Adolescent; Adult; Age Factors; Aged; Algorithms; Blood Glucose; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Life Style; Middle Aged; Risk Factors; Time Factors

Insulin glargine is an analogue of human insulin that is modified to provide a consistent level of plasma insulin over a long duration. Pharmacokinetic and pharmacodynamic studies show that a single injection of insulin glargine leads to a smooth 24-hour time-action profile with no undesirable pronounced peaks of activity. In clinical trials, this profile has been associated with at least equivalent, if not better, glycemic control than other traditional basal insulins and a significantly lower rate of overall and nocturnal hypoglycemia. The convenience of a once-daily injection, a lack of need for resuspension (insulin glargine is a clear solution when injected), and lower rates of hypoglycemia should translate into improvements in patient treatment satisfaction. This review appraises the evidence for the view that insulin glargine represents an advance in basal insulin therapy for both type 1 and type 2 diabetes patients.

Topics: Blood Glucose; Cardiovascular Diseases; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Patient Compliance; Patient Satisfaction; Practice Guidelines as Topic; Risk Factors; Treatment Outcome

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes between meals and overnight as well as postprandially. The most frequently used insulin for basal therapy is the intermediate-acting neutral protamin Hagedorn (NPH) insulin, although it does not correspond to a physiological profile. Insulin glargine is a new extended-action recombinant insulin analog, which is absorbed slowly into the bloodstream, reaching peak action in about 4 h and maintaining this concentration profil for 24-30 h. Some studies demonstrated that insulin glargine reduces the incidence of hypoglycemia and is at least as effective as NPH insulin given once or twice daily. It is equally effective administered before breakfast, dinner or at bedtime. Similar absorption rates were recorded after subcutaneous injection in differents part of body. The continuous subcutaneous insulin infusion utilizing an external insulin infusion pump (CSII) is one approach to intensive insulin therapy. Some studies indicate that pump therapy is associated with improved glycemic control compared with traditional insulin therapies and with significant decreases in frequency of both mild and severe hypoglycemic episodes. The author summarizes the indication, the effect and side effects of pump therapy.

Topics: Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity

Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes.. All studies were 24-28 weeks long, except one 52-week study, for which interim 20-week data were used.. Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA(1c) (< or =7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively.. These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA(1c) target of < or =7.0% in patients with type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

This article reviews our current understanding of the etiology, presentation, and management of type 1 diabetes. The discussion includes a review of the natural history of diabetes, the complex relationship between genetic and environmental risk for type 1 diabetes, and current methods for prediction of type 1 diabetes. The article also reviews the current management of children who have new-onset type 1 diabetes, age-appropriate management goals, and diabetes complications. Finally, the article discusses the future of diabetes screening programs and the progress toward the ultimate goal of curing type 1 diabetes.

Topics: Autoantibodies; Blood Glucose; Child; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Genetic Predisposition to Disease; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Nutrition Therapy

Despite many improvements in the treatment of type 1 diabetes mellitus (DM1), the non-physiological time-action profiles of conventional insulins remain a significant obstacle. In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular and NPH insulin. The rapid insulin analogs used as prandial and the long-acting insulin analogs used as basal simulate physiological insulin profiles more closely than the older conventional insulins. The efficacy of insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in DM1 has been established in pediatric patients. Insulin pumps have improved since they were first introduced. CSII therapy may provide an effective alternative for selected pediatric patients with DM1. In most studies at pediatric age, CSII therapy resulted in a improvement in HbA1c, a decreased rate of hypoglycemia without an abnormal increase in BMI, and without adversely affecting psychosocial outcomes in children and adolescents with DM1.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting

A better diabetes regulation seems possible, with the aid of the recently available insulin analogs than with isophane insulin, for patients with diabetes mellitus type 1 or 2. The glycaemic regulation can be improved and/or the chances of hypoglycaemia can be reduced by reduced variability in the resorption of (insulin glargine) or by binding to the serum albumin (insulin detemir). With poor regulation it seems possible to bring about a substantial HbA1c reduction without an increase in hypoglycaemic incidents, and with reasonable to good regulation to achieve a reduction of the number of hypoglycaemias whilst HbA1c remains the same.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness.. Electronic databases.. A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine.. Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control. Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended model. Three economic models are provided in the submission, two relating to type 1 diabetes and one relating to type 2 diabetes. All three models compare the cost--utility of insulin glargine against NPH insulin. In general, the structures of the models are poor and in all three models, mistakes relating to assumptions and calculations have been made. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons. The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia.. The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes. Further research into insulin glargine is needed that addresses the quality of life issues associated with fear of hypoglycaemia and also the economic impact of balance of HbA1c control and incidence of hypoglycaemia achieved in practice. Studies examining the economic evidence on insulin glargine should be published.

Topics: Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome

Tight glycaemic control (ideally, HbA1c<7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes.

Topics: Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Parenteral; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

The pharmacodynamics, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of insulin glargine are reviewed. Current treatment regimens for patients with type 1 diabetes mellitus and some with type 2 are designed to provide a basal insulin level with intermittent preprandial insulin coverage. Insulin glargine precipitates after subcutaneous injection, slowing absorption. Insulin glargine is used as a basal insulin and exhibits a flat pharmacokinetic profile, with a duration of action of at least 24 hours. Hypoglycemia is the most commonly reported adverse effect, especially within the first four weeks after a switch to insulin glargine. Insulin glargine should not be mixed with any other insulin product and should be administered with a syringe that has not been used for other insulin products or other medications. Insulin glargine is administered once daily at bedtime. Patients previously receiving twice-daily isophane insulin (NPH) should receive an insulin glargine dosage 20% less than the total daily dose of NPH insulin. Clinical trials did not consistently show improvements in hemoglobin A1c levels when patients with type 1 diabetes mellitus were switched from NPH insulin once or twice daily to insulin glargine. Insulin glargine should be considered for patients who continue to have elevated morning blood glucose levels and problems with nocturnal hypoglycemia despite receiving NPH insulin at bedtime. In patients with type 2 diabetes mellitus, insulin glargine significantly improved glycemic control compared with once-daily NPH insulin, but not when it was compared with combined treatment with once- or twice-daily NPH insulin. Clinical trials assessing progression of retinopathy and nephropathy and comparing insulin glargine therapy with continuous subcutaneous insulin infusion therapy are needed to more clearly determine insulin glargine's role. Insulin glargine is a new long-acting formulation that can provide prolonged basal glucose control in patients with diabetes mellitus.

Topics: Area Under Curve; Diabetes Mellitus; Drug Costs; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Insulin glargine is a recombinant human insulin analogue produced by DNA technology using a nonpathogenic strain of Escherichia coli. Two modifications of human insulin result in a stable molecule which is soluble in slightly acidic conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue. Because of these properties, absorption of insulin glargine is delayed and the analogue provides a fairly constant, basal insulin supply without peaks in plasma insulin levels for approximately 24 hours, similar to that achieved by a continuous subcutaneous insulin infusion. Insulin glargine is indicated as a once daily subcutaneous injection to provide basal glycaemic control in adults and children aged >6 years with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Fasting plasma glucose and fasting blood glucose levels generally improved to a greater extent in patients with type 1 diabetes mellitus receiving insulin glargine than patients who administered Neutral Protamine Hagedorn (NPH) insulin. In patients with type 1 or 2 disease, glycosylated haemoglobin levels were slightly reduced and to a similar extent with insulin glargine and NPH insulin. Most clinical trials in patients with type 1 or 2 diabetes mellitus demonstrated a lower incidence of hypoglycaemia, especially nocturnal hypoglycaemia, compared with NPH insulin. One of the most common adverse events with insulin glargine treatment was injection site pain which, in some studies, occurred more frequently than in patients receiving NPH insulin. In all cases the symptoms were mild and treatment discontinuation was not required. Otherwise, the drug is well tolerated and does not appear to be immunogenic.. Insulin glargine once a day provides basal control of glycaemia for approximately 24 hours without inducing peaks in plasma insulin levels in patients with type 1 or 2 diabetes mellitus. In long term, well designed trials insulin glargine once daily improved glycaemic control at least as effectively as NPH insulin given once or twice daily. The drug was well tolerated and in most studies the incidence of nocturnal hypoglycaemia was significantly less in patients treated with insulin glargine compared with patients receiving NPH insulin. Therefore, insulin glargine is likely to be a useful addition to the armamentarium of insulin therapy by establishing basal glycaemic control with once daily administration and a reduced risk of nocturnal hypoglycaemia.

Topics: Absorption; Area Under Curve; Blood Glucose; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Patient Satisfaction; Randomized Controlled Trials as Topic; Treatment Outcome

In diabetes mellitus, the clinical goal of intensive glycemic control (lowering blood glucose concentrations to normal or near-normal levels) has been hindered by the lack of insulin regimens that duplicate the basal-bolus secretion of insulin by the healthy pancreas. In particular, intensive therapy has been associated with a risk of hypoglycemia.. This article reviews the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, and potential drug interactions of insulin glargine, a new long-acting recombinant human insulin analogue. Results of clinical trials of its efficacy and tolerability as a basal insulin in the treatment of type 1 and type 2 diabetes are summarized.. Primary research and review articles on insulin glargine were identified through a search of MEDLINE from 1966 to July 2001. Abstracts were identified through a search of the Institute for Scientific Information Web of Science from 1995 to July 2001 and proceedings of American Diabetes Association scientific meetings. Additional information was obtained from the product information for insulin glargine. All identified articles and abstracts were evaluated for relevance, and all relevant information was included in the review. Priority was given to data from the primary medical literature.. Insulin glargine has a slower onset of action than human neutral protamine Hagedorn (NPH) insulin, a longer duration of action (up to 24 hours), and no pronounced peak. It has similar tolerability and produces similar glycemic control to once- or twice-daily human NPH insulin, with a similar glucose-lowering effect on a molar basis. A decreased incidence of hypoglycemia, particularly at night, has been reported with insulin glargine compared with human NPH insulin. Insulin glargine appears to be comparable to human NPH insulin in terms of toxicity, adverse effects, immunogenicity, and potential for drug interactions. Results of clinical trials of insulin glargine in both type 1 and type 2 diabetes support its use in combination with a short-acting insulin, insulin lispro, or oral antidiabetic medications. Although insulin glargine cannot be mixed with other insulin preparations, it has the potential convenience of providing basal insulin with once-daily bedtime dosing.. Based on the as yet small amount of data from full clinical study reports in peer-reviewed publications, insulin glargine appears to be a well-tolerated and effective basal insulin preparation for patients with type 1 or type 2 diabetes (including pediatric patients). Its delayed onset of action and prolonged, flat time-action profile mimic the action of endogenous basal insulin (or an insulin pump), decreasing the risk of hypoglycemic episodes. Insulin glargine may be a useful new option for meeting overnight insulin requirements, although most patients will require a rapid-acting insulin such as insulin lispro with or before meals for optimal management of blood glucose levels.

Topics: Adult; Child; Diabetes Mellitus; Drug Interactions; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dogs; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Swine; Time Factors

To describe the phase 3a ONWARDS clinical development programme investigating insulin icodec (icodec), a once-weekly basal insulin, including the design and rationale for each of the ONWARDS 1-6 trials.. Six randomized controlled trials have been initiated in adults with type 2 diabetes (T2D) (insulin-naive: ONWARDS 1, 3 and 5; previously insulin-treated: ONWARDS 2 and 4) and type 1 diabetes (T1D) (ONWARDS 6). Each trial will investigate icodec use in a unique clinical scenario, with consideration of long-term safety and varied comparator treatments (insulin glargine U100 or U300 or insulin degludec). ONWARDS 5 will incorporate real-world elements and a digital dose titration solution to guide icodec dosing. The primary objective for each of the trials is to compare the change in HbA1c from baseline to week 26 or week 52 between icodec and comparator arms. Secondary objectives include investigating other glycaemic control and safety parameters, such as fasting glucose, time in glycaemic range and hypoglycaemia. Patient-reported outcomes will assess treatment satisfaction.. The ONWARDS 1-6 trials will evaluate the efficacy and safety of once-weekly icodec compared with currently available daily basal insulin analogues in T2D and T1D. These trials will generate comprehensive evidence of icodec use in diverse populations across the spectrum of diabetes progression and treatment experience.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

To use continuous glucose monitoring (CGM)-based time-in-range (TIR) as a primary efficacy endpoint to compare the second-generation basal insulin (BI) analogues insulin glargine 300 U/ml (Gla-300) and insulin degludec 100 U/ml (IDeg-100) in adults with type 1 diabetes (T1D).. InRange was a 12-week, multicentre, randomized, active-controlled, parallel-group, open-label study comparing glucose TIR and variability between Gla-300 and IDeg-100 using blinded 20-day CGM profiles. The inclusion criteria consisted of adults with T1D treated with multiple daily injections, using BI once daily and rapid-acting insulin analogues for at least 1 year, with an HbA1c of 7% or higher and of 10% or less at screening.. Overall, 343 participants were randomized: 172 received Gla-300 and 171 IDeg-100. Non-inferiority (10% relative margin) of Gla-300 versus IDeg-100 was shown for the primary endpoint (percentage TIR ≥ 70 to ≤ 180 mg/dl): least squares (LS) mean (95% confidence interval) 52.74% (51.06%, 54.42%) for Gla-300 and 55.09% (53.34%, 56.84%) for IDeg-100; LS mean difference (non-inferiority): 3.16% (0.88%, 5.44%) (non-inferiority P = .0067). Non-inferiority was shown on glucose total coefficient of variation (main secondary endpoint): LS mean 39.91% (39.20%, 40.61%) and 41.22% (40.49%, 41.95%), respectively; LS mean difference (non-inferiority) -5.44% (-6.50%, -4.38%) (non-inferiority P < .0001). Superiority of Gla-300 over IDeg-100 was not shown on TIR. Occurrences of self-measured and CGM-derived hypoglycaemia were comparable between treatment groups. Safety profiles were consistent with known profiles, with no unexpected findings.. Using clinically relevant CGM metrics, InRange shows that Gla-300 is non-inferior to IDeg-100 in people with T1D, with comparable hypoglycaemia and safety profiles.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

To explore the effect of active insulin titration versus usual titration on glycaemic control in patients with type 2 diabetes mellitus uncontrolled with oral antidiabetic drugs (OADs).. In a 24-week, prospective and randomized study, 172 patients with uncontrolled type 2 diabetes were randomly assigned to either active titration or usual titration. Efficacy and safety outcomes included changes in glycated haemoglobin (HbA1c) and fasting plasma glucose, percentage of individuals achieving HbA1c<53 mmol/mol, and hypoglycaemic events.. At Week 24, change in HbA1c was -1.08% ± 1.60% in the active titration group and -0.95% ± 1.34% in the usual titration group (P = 0.569). The percentages of individuals achieving HbA1c<53 mmol/mol were 29.4% and 16.1% in the active and usual titration groups, respectively (P = 0.037). There was no significant difference in the incidence of hypoglycaemia between the two groups. Multivariate logistic regression indicated that, with active titration, baseline HbA1c levels and postprandial glucose excursion were significantly associated with achieving HbA1c<53 mmol/mol.. Addition of basal insulin using active titration for 24 weeks provided a higher rate of HbA1c target achievement without significant hypoglycaemia compared to usual titration in individuals with uncontrolled type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Prospective Studies

To determine the effectiveness and safety of early combination of insulin glargine with intravenous (IV) insulin infusion compared with IV insulin infusion alone in the management of diabetic ketoacidosis (DKA).. This was a single-centre, open-label, randomized controlled trial of adults aged 18 years or older diagnosed with DKA. The 'early glargine' group was given subcutaneous insulin glargine 0.3 units/kg within the first 3 hours of DKA diagnosis, in addition to the standard IV insulin infusion. The control group received standard IV insulin treatment only. The primary outcome was the time to DKA resolution. The other outcomes included rebound hyperglycaemia, mortality, hypoglycaemia and hypokalaemia, as well as the length of hospital stay (LOS).. A total of 60 patients (30 patients per group) were enrolled. Most patients (76.7%) had type 2 diabetes. Both groups were similar in baseline characteristics, except for higher serum beta-hydroxybutyrate and lower pH levels in the early glargine group. The mean ± standard deviation time to DKA resolution in the early glargine group was significantly faster than the control group (9.89 ± 3.81 vs. 12.73 ± 5.37 hours; P = .022). The median (interquartile range) LOS was significantly shorter in the early glargine group than in the control group (4.75 [3.53-8.96] vs. 15.25 [5.71-26.38] days; P = .024). The incidence of rebound hyperglycaemia, all-cause mortality, hypoglycaemia and hypokalaemia was similar between the groups.. Early combination of insulin glargine with IV insulin infusion led to a faster DKA resolution and a shorter LOS, without increasing hypoglycaemia and hypokalaemia.

Topics: Adult; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Hypokalemia; Insulin; Insulin Glargine; Insulin, Regular, Human

To compare efficacy and safety of degludec 100 IU/mL (Deg-100) and glargine 300 IU/mL (Gla-300) in adults with type 1 diabetes.. Open-label, single-center, randomized, parallel-group, 24-week trial in adults with type 1 diabetes, on basal-bolus insulin therapy, HbA1c ≤ 10%, using self-monitoring blood glucose. Participants were randomized 1:1 to a basal-bolus insulin regimen with Deg-100 (N = 129) or Gla-300 (N = 131). Primary efficacy endpoint: mean change in HbA1c from baseline to week-24. Main safety outcome: incidence rate of hypoglycemia during the study. Quality of life (DQOL) and satisfaction with diabetes treatment (DTSQ) were assessed.. At week 24, after adjusting for baseline HbA1c, the decrease in HbA1c did not differ between groups: Deg-100 (-0.07 ± 0.7%) and Gla-300 (-0.16 ± 0.77%) (P = 0.320). There were no significant differences between groups in HbA1c, nocturnal hypoglycemia, severe hypoglycemia, DQOL, or DTSQ scores. The incidence rates of hypoglycemia < 3.9 mmol/L (Deg-100: 115.24 events/person-year vs Gla-300: 99.01 events/person-year, p < 0.001); and < 3.0 mmol/L (Deg-100: 41.17 events/person-year vs Gla-300: 34.29 events/person-year, p < 0.001) were different between groups.. Deg-100 and Gla-300 have similar metabolic efficacy, incidence ratio of nocturnal and severe hypoglycemia, DQOL and DTSQ scores. Differences in the incidence rate of hypoglycemia < 3.9 mmol/L and < 3.0 mmol/L should be confirmed.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Quality of Life

To compare nocturnal glucose profiles according to hourly plasma glucose measurements during treatment with insulin degludec and insulin glargine U100 in a cohort of people with type 1 diabetes prone to nocturnal severe hypoglycaemia.. The HypoDeg trial is a 2-year investigator-initiated, randomized, controlled crossover trial in 149 participants randomized to treatment with insulin degludec and insulin glargine U100 for 12 months each. The 51 participants in this predefined substudy stayed at least one night in hospital during each treatment arm for plasma glucose samples to be taken. Endpoints were glucose profiles, including mean plasma glucose, glycaemic variability and risk of hypoglycaemia.. There were no differences between treatments regarding mean plasma glucose. We saw a flatter glucose profile during insulin degludec compared with insulin glargine U100 treatment, which had a nadir at 4:00 AM, with a subsequent rise. During treatment with insulin degludec, the participants had lower glycaemic variability, with an estimated treatment difference of -4.3% (95% confidence interval [CI] -8.1 to -0.5; P < 0.05). Participants treated with insulin degludec were less likely to experience nocturnal hypoglycaemia below 3.0 mmol/L (hazard ratio 0.36 [95% CI 0.17-0.73; P < 0.05]).. Based on nocturnal plasma glucose measurements, treatment with insulin degludec compared with insulin glargine U100 administered in the evening results in lower glycaemic variability and lower risk of nocturnal hypoglycaemia without differences in mean plasma glucose.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

It is generally recommended to reduce basal insulin doses after exercise to reduce the risk of post-exercise nocturnal hypoglycaemia. Based on its long t. The ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise test in the afternoon. All participants wore blinded continuous glucose monitors for 6 days, measuring the incidence of (nocturnal) hypoglycaemia and subsequent glucose profiles.. Post-exercise adjustment of degludec does not mitigate the risk of subsequent nocturnal hypoglycaemia in people with type 1 diabetes. Although reducing degludec reduced next-day time below range, this did not translate into fewer hypoglycaemic events, while postponing degludec should be avoided because of increased time above range. Altogether, these data do not support degludec dose adjustment after a single exercise bout.. EudraCT number 2019-004222-22 FUNDING: The study was funded by an unrestricted grant from Novo Nordisk, Denmark.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Exercise; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged

Basal Insulin Fc (BIF; insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed safety and efficacy of BIF versus degludec in 265 patients with type 1 diabetes (T1D) using multiple daily injections.. During this randomized, parallel, open-label study, patients with T1D were randomized (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to a fasting glucose level of 80-100 mg/dL. The primary end point was HbA1c change from baseline to week 26 (noninferiority margin, 0.4%). Secondary end points included percent time in range (TIR) (70-180 mg/dL), continuous glucose monitoring (CGM) fasting glucose (FG) level, and rate of hypoglycemia.. After 26 weeks, patients receiving BIF had noninferior HbA1c change from baseline versus those receiving degludec, with a statistically significant treatment difference of 0.17% (90% CI 0.01, 0.32; P = 0.07) favoring the comparator. Percent TIR was similar for patients in the BIF (56.1%) and degludec (58.9%; P = 0.112) groups at week 26. FG values were significantly higher for patients receiving BIF (158.8 mg/dL) versus degludec (143.2 mg/dL; P = 0.003). Rates of CGM-derived hypoglycemia were not statistically significantly different for BIF and degludec over 24 h for level 1 (P = 0.960) or level 2 (P = 0.517) hypoglycemia during the treatment period. Occurrence of serious adverse events was similar between the BIF and degludec groups.. Once-weekly BIF demonstrated noninferior glycemic control to once-daily degludec (treatment difference: 0.17% favoring degludec) and no difference in hypoglycemia or other safety findings in patients with T1D.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

Basal insulin Fc (BIF) (insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed the safety and efficacy of BIF versus degludec in insulin-naive patients with type 2 diabetes (T2D) previously treated with oral antihyperglycemic medications.. During this randomized, parallel, open-label study, 278 insulin-naive patients with T2D were randomly assigned (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to fasting glucose of 80-100 mg/dL (4.4 to <5.6 mmol/L). The primary end point was HbA1c change from baseline to week 26 (noninferiority margin 0.4%). Secondary end points included fasting blood glucose (FBG), six-point glucose profiles, and rate of hypoglycemia.. After 26 weeks of treatment, BIF demonstrated a noninferior HbA1c change from baseline versus degludec, with a treatment difference of 0.06% (90% CI -0.11, 0.24; P = 0.56). Both BIF and degludec treatment led to significant reductions in FBG from baseline. At week 26, the between-treatment difference for BIF versus degludec was 4.7 mg/dL (90% CI 0.1, 9.3; P = 0.09). The rate of level 2 hypoglycemia was low and not significantly different between treatment groups (BIF 0.22 events/patient/year, degludec 0.15 events/patient/year; P = 0.64); there was no severe hypoglycemia. The occurrence of treatment-emergent adverse events was also similar between BIF and degludec.. Once-weekly BIF achieved excellent glycemic control similar to degludec, with no concerning hypoglycemia or other safety findings.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

To assess insulin glargine 100 U/mL (IGlar-100) treatment outcomes according to newly-defined subgroups of type 2 diabetes mellitus (T2DM).. Insulin-naïve T2DM participants (n = 2684) from nine randomised clinical trials initiating IGlar-100 were pooled and assigned to subgroups "Mild Age-Related Diabetes (MARD)", "Mild Obesity Diabetes (MOD)", "Severe Insulin Resistant Diabetes (SIRD)", and "Severe Insulin Deficient Diabetes (SIDD)", according to age at onset of diabetes, baseline HbA1c, BMI, and fasting C-peptide using sex-specific nearest centroid approach. HbA1c, FPG, hypoglycemia, insulin dose, and body weight were analysed at baseline and 24 weeks.. Subgroup distribution was MARD 15.3 % (n = 411), MOD 39.8 % (n = 1067), SIRD 10.5 % (n = 283), SIDD 34.4 % (n = 923). From baseline HbA1c 8.0-9.6% adjusted least square mean reductions after 24 weeks were similar between subgroups (1.4-1.5 %). SIDD was less likely to achieve HbA1c < 7.0 % (OR: 0.40 [0.29, 0.55]) than MARD. While the final IGlar-100 dose (0.36 U/kg) in MARD was lower than in other subgroups (0.46-0.50 U/kg), it had the highest hypoglycemia risk. SIRD had lowest hypoglycemia risk and SIDD exhibited greatest body weight gain.. IGlar-100 lowered hyperglycemia similarly in all T2DM subgroups, but level of glycemic control, insulin dose, and hypoglycemia risk differed between subgroups.

Topics: Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Male

This subanalysis of the SoliMix trial assessed the efficacy and safety of advancing basal insulin (BI) therapy with iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D) living in Latin American (LATAM) countries, i.e. Argentina and Mexico (N = 160).. SoliMix (EudraCT: 2017-003370-13) was a 26-week, open-label, multicentre study, where adults with T2D suboptimally controlled with BI plus one or two oral glucose-lowering drugs and glycated haemoglobin (HbA1c) ≥7.5% to ≤10% were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30.. Both primary efficacy endpoints were met in the LATAM region. After 26 weeks, HbA1c was reduced by 1.8% with iGlarLixi and 1.4% with BIAsp 30, meeting non-inferiority [least squares mean difference -0.47% (95% confidence interval: -0.82, -0.11); p < .001]. iGlarLixi was superior to BIAsp 30 for body weight change [least squares mean difference -1.27% (95% confidence interval: -2.41, -0.14); p = .028]. iGlarLixi was also superior to BIAsp 30 for HbA1c reduction (p = .010). A greater proportion of participants achieved HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycaemia with iGlarLixi versus BIAsp 30. Incidence and rates of American Diabetes Association Level 1 and 2 hypoglycaemia were lower with iGlarLixi versus BIAsp 30.. Once-daily iGlarLixi provided better glycaemic control with weight benefit and less hypoglycaemia than twice-daily premix BIAsp 30. iGlarLixi may be a favourable alternative to premix BIAsp 30 in people with suboptimally controlled T2D to advance BI therapy in the LATAM region.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Latin America; Treatment Outcome; Weight Gain

Insulin icodec is an investigational once-weekly basal insulin analogue for diabetes management.. We conducted a 78-week randomized, open-label, treat-to-target phase 3a trial (including a 52-week main phase and a 26-week extension phase, plus a 5-week follow-up period) involving adults with type 2 diabetes (glycated hemoglobin level, 7 to 11%) who had not previously received insulin. Participants were randomly assigned in a 1:1 ratio to receive once-weekly insulin icodec or once-daily insulin glargine U100. The primary end point was the change in the glycated hemoglobin level from baseline to week 52; the confirmatory secondary end point was the percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52. Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded.. Each group included 492 participants. Baseline characteristics were similar in the two groups. The mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec than with glargine U100 (from 8.50% to 6.93% with icodec [mean change, -1.55 percentage points] and from 8.44% to 7.12% with glargine U100 [mean change, -1.35 percentage points]); the estimated between-group difference (-0.19 percentage points; 95% confidence interval [CI], -0.36 to -0.03) confirmed the noninferiority (P<0.001) and superiority (P = 0.02) of icodec. The percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec than with glargine U100 (71.9% vs. 66.9%; estimated between-group difference, 4.27 percentage points [95% CI, 1.92 to 6.62]; P<0.001), which confirmed superiority. Rates of combined clinically significant or severe hypoglycemia were 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98 to 2.75) and 0.30 and 0.16 events per person-year of exposure, respectively, at week 83 (estimated rate ratio, 1.63; 95% CI, 1.02 to 2.61). No new safety signals were identified, and incidences of adverse events were similar in the two groups.. Glycemic control was significantly better with once-weekly insulin icodec than with once-daily insulin glargine U100. (Funded by Novo Nordisk; ONWARDS 1 ClinicalTrials.gov number, NCT04460885.).

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

To determine the efficacy and safety of once-weekly dulaglutide added to basal insulin in Chinese patients with type 2 diabetes mellitus (T2DM) with inadequate glycaemic control.. In the phase III, double-blind AWARD-CHN3 study, Chinese patients with T2DM (N = 291) and glycated haemoglobin (HbA1c) ≥7.0% and ≤11.0% receiving stable doses of basal insulin glargine with metformin and/or acarbose were randomized (1:1) to receive add-on dulaglutide 1.5 mg once weekly or placebo once weekly. The primary endpoint was the superiority of dulaglutide/glargine to placebo/glargine for change from baseline in HbA1c at Week 28.. The least squares (LS) mean ± standard error change in HbA1c from baseline to Week 28 was -2.0 ± 0.08% with dulaglutide/glargine and -1.1 ± 0.07% with placebo/glargine (LS mean difference: -1.0%, 95% confidence interval [CI] -1.1 to -0.8; P < 0.001), and more patients receiving dulaglutide/glargine achieved HbA1c levels <7.0% (75.9% vs. 33.8%; P < 0.001 vs. placebo/glargine). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: -1.2 kg, 95% CI -1.8 to - 0.6; P < 0.001). Reductions in fasting serum glucose were greater with dulaglutide/glargine than with placebo/glargine (LS mean difference: -0.8 mmol/L, 95% CI -1.1 to - 0.5; P < 0.001). The incidence of hypoglycaemia was similar with dulaglutide/glargine and placebo/glargine (29.2% vs. 31.3%; P = 0.704); no patient in either group had severe hypoglycaemia. The most common treatment-emergent adverse events with dulaglutide/glargine were decreased appetite (22.2%), diarrhoea (13.2%) and nausea (10.4%).. Dulaglutide added to basal insulin was efficacious and well tolerated in Chinese patients with T2DM.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; East Asian People; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin Glargine; Recombinant Fusion Proteins

Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.. To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice.. 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626).. 176 sites in 7 countries.. 1085 insulin-naive adults with T2D.. Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300).. The primary outcome was change in glycated hemoglobin (HbA. The estimated mean change in HbA. Inability to differentiate the effects of icodec and the dosing guide app.. Compared with OD analogues, icodec with app showed superior HbA. Novo Nordisk A/S.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Mobile Applications

Rosenstock J, Bain SC, Gowda A, et al; ONWARDS 1 Trial Investigators.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described.. To assess the efficacy and safety of tirzepatide vs insulin lispro as an adjunctive therapy to insulin glargine.. This open-label, phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020, to November 1, 2022) in 1428 adults with type 2 diabetes taking basal insulin.. Participants were randomized (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).. Outcomes included noninferiority of tirzepatide (pooled cohort) vs insulin lispro, both in addition to insulin glargine, in HbA1c change from baseline at week 52 (noninferiority margin, 0.3%). Key secondary end points included change in body weight and percentage of participants achieving hemoglobin A1c (HbA1c) target of less than 7.0%.. Among 1428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was -2.1% vs -1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, -0.98% [95% CI, -1.17% to -0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was -9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, -12.2 kg [95% CI, -13.4 to -10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro.. In people with inadequately controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared with prandial insulin as an additional treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia.. ClinicalTrials.gov Identifier: NCT04537923.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Internationality; Male; Middle Aged; Treatment Outcome

To investigate whether the long-acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D).. Adults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2-year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal-bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run-in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention-to-treat.. Treatment with insulin degludec resulted in a 28% (95% CI: 9%-43%; P = .02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%-53%; P = .002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%-58%; P = .04) RRR in all-day severe hypoglycaemia compared with insulin glargine U100.. Patients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all-day severe hypoglycaemia with insulin degludec compared with insulin glargine U100.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Prospective Studies

To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD).. After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (-21 mmol/mol; -1.9%) compared with iGlar (-16 mmol/mol; -1.4%; P < 0.0001) and Lixi (-10 mmol/mol; -0.9%; P < 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2-hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference -1.1 kg; P < 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant-year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%).. iGlarLixi achieved significant HbA1c reductions, to near-normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well-tolerated treatment option for Asian Pacific people with T2D.

Topics: Administration, Oral; Adult; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Metformin; Middle Aged; Peptides; Sodium-Glucose Transporter 2 Inhibitors; Weight Gain

To investigate whether an increased bolus: basal insulin ratio (BBR) with liver-targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycaemic events (HEv).. We enrolled 52 persons (HbA1c 6.9% ± 0.12%, mean ± SEM) with type 1 diabetes using multiple daily injections. Hepatic-directed vesicle (HDV) was used to deliver 1% of peripheral injected BoI to the liver. A 90-day run-in period was used to introduce subjects to unblinded continuous glucose monitoring and optimize standard basal insulin (BaI) (degludec) and BoI (lispro) dosing. At 90 days, BoI was changed to HDV-insulin lispro and subjects were randomized to an immediate 10% or 40% decrease in BaI dose.. At 90 days postrandomization, total insulin dosing was increased by ~7% in both cohorts. The -10% and -40% BaI cohorts were on 7.7% and 13% greater BoI with 6.9% and 30% (P = .02) increases in BBR, respectively. Compared with baseline at randomization, nocturnal level 2 HEv were reduced by 21% and 43%, with 54% and 59% reductions in patient-reported HEv in the -10% and -40% BaI cohorts, respectively.. Our study shows that liver-targeted BoI safely decreases HEv and symptoms without compromising glucose control. We further show that with initiation of liver-targeted BoI, the BBR can be safely increased by significantly lowering BaI dosing, leading to greater BoI usage.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulin, Regular, Human; Liver

To compare the efficacy and safety of once-weekly (OW) semaglutide versus thrice-daily (TID) insulin aspart (IAsp) in participants with inadequately controlled type 2 diabetes (T2D) treated with insulin glargine (IGlar) and metformin.. SUSTAIN 11 (NCT03689374) was a randomized (1:1), parallel, open-label, multinational, phase 3b trial. After a 12-week run-in to optimize once-daily IGlar U100, 1748 adults with T2D (HbA1c >7.5% to ≤10.0%) were randomized to OW semaglutide or TID IAsp as add-on to optimized IGlar and metformin for 52 weeks. The primary outcome was change in HbA1c from randomization to week 52. Confirmatory secondary endpoints included the occurrence of severe hypoglycaemic episodes and change in body weight (BW). Safety was assessed.. HbA1c (randomization: 8.6% [70.0 mmol/mol]) decreased by 1.5% points (16.6 mmol/mol) and 1.2% points (13.4 mmol/mol) with semaglutide (n = 874) and IAsp (n = 874), respectively (estimated treatment difference [ETD] -0.29% points [95% confidence interval {CI} -0.38; -0.20]; P < .0001 for non-inferiority). Few severe hypoglycaemic episodes were recorded in either group, with no statistically significant difference between the groups. Change in BW from randomization (87.9 kg) to week 52 was in favour of semaglutide (-4.1 kg) versus IAsp (+2.8 kg) (ETD -6.99 kg [95% CI -7.41; -6.57]). A higher proportion of participants experienced adverse events with semaglutide (58.5%) versus IAsp (52.1%); most were mild to moderate.. In this basal insulin-treated population, OW semaglutide improved glycaemic control to a greater extent than TID IAsp and provided numerically greater weight loss.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Metformin; Treatment Outcome

To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China.. This open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint).. There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group.. Compared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Metformin

The objective of this study was to compare initiation of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) vs insulin glargine U100 (iGlar) along with gliclazide, exclusively in people of South Asian origin with type 2 diabetes (T2D).. The Variability of glucose Assessed in a Randomized trial comparing the Initiation of A Treatment approach with biosimilar basal Insulin analog Or a titratable iGlarLixi combinatioN in type 2 diabetes among South Asian participants (VARIATION 2 SA) trial (ClinicalTrials.gov identifier: NCT03819790) randomized insulin-naïve adults with T2D having glycated hemoglobin (A1C) 7.1% to 11% to initiate either iGlarLixi or iGlar + gliclazide. Insulin doses were titrated similarly to a prebreakfast glucose target of 4.0 to 5.5 mmol/L. Average time in range (TIR) on a masked continuous glucose monitor (CGM), A1C, fasting plasma glucose (FPG) and weight were assessed at the end of the 12-week treatment period.. Mean baseline characteristics for the 104 randomized participants were similar between treatment groups, including the following: age, 59±11 years; diabetes duration, 13.7±7.3 years; and A1C, 8.5%±1.2%. Coprimary outcomes of average TIRs within 24- and 12-h (6 am to 6 pm) periods at the end of trial were 70.5%±16.8% and 72.9%±17.6% for iGlarLixi, whereas these TIRs were 65.6%±21.6% and 67.3%±20.7% for the iGlar + gliclazide regimen, respectively, with no significant differences between groups (p=0.35 for 24-h TIR and p=0.14 for 12-h TIR). No significant difference in secondary outcomes was observed between treatment groups. Self-reported hypoglycemic events throughout the trial period and CGM-reported hypoglycemia (<4 and <3 mmol/L) were similar between randomized treatments.. Initiation of iGlarLixi resulted in similar TIR, A1C, FPG, weight and hypoglycemia compared with the more affordable option of starting iGlar + gliclazide in adults of South Asian origin with T2D.

Topics: Adult; Aged; Biosimilar Pharmaceuticals; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Gliclazide; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Middle Aged

To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs.. LixiLan-L-CN (NCT03798080) was a 30-week randomized, active-controlled, open-label, parallel-group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30.. iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long-standing T2D advancing therapy from basal insulin.

Topics: Adult; Blood Glucose; China; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Middle Aged; Obesity; Peptides

To better understand outcomes in people with type 2 diabetes at high risk of hypoglycemia, we conducted post hoc analyses in subgroups of participants from the real-world ACHIEVE Control study (NCT02451137) with ≥1 hypoglycemia risk factor.. Insulin-naive adults with type 2 diabetes and A1c ≥8% were randomized 1:1 to insulin glargine 300 U/mL (Gla-300) or standard-of-care basal insulin (SOC-BI). Participants had documented history of ≥1 risk factors for hypoglycemia: chronic kidney disease, cardiovascular disease, dementia or blindness, age ≥65 years, or history of hypoglycemia. Outcomes included individualized A1c target attainment without documented symptomatic hypoglycemia (blood glucose [BG] ≤3.9 mmol/L or <3.0 mmol/L) or severe hypoglycemia, A1c target attainment, and absence of documented symptomatic or severe hypoglycemia at 6 and 12 months.. Within subgroups, odds ratios generally showed trends favoring Gla-300 versus SOC-BI, particularly for hypoglycemia avoidance in participants ≥65 years of age (BG ≤3.9 mmol/L; odds ratio, 1.52; 95% confidence interval, 1.14-2.03) and those with chronic kidney disease (BG ≤3.9 mmol/L; odds ratio, 2.28; 95% confidence interval, 1.26-4.12). Results were consistent with the overall population.. These data suggest potential benefit of Gla-300 versus SOC-BI for avoiding hypoglycemia in participants with ≥1 hypoglycemia risk factor.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA. HbA. Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM.. EudraCT 2015-001167-39.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Female; Follow-Up Studies; Glycemic Control; Humans; Hypoglycemia; Incidence; Insulin Glargine; Italy; Male; Middle Aged; Physician-Patient Relations; Physicians; Retrospective Studies; Self-Management; Titrimetry

This pilot, randomized, open-label controlled study compared the basal-bolus regimens of insulin glargine (IG) and neutral protamine Hagedorn (NPH) insulin in stroke patients with hyperglycemia receiving intensive care. The study recruited acute stroke patients requiring intensive care within 72 h (h) of onset and had blood glucose > 200 mg/dL. 50 patients received IG (n = 26) or NPH (n = 24) with added short-acting prandial regular insulin over a 72-h period. The primary end point was the percentage of glucose within 80-180 mg/dL assessed through continuous glucose monitoring. The baseline characteristics were comparable, except the IG had higher glucose pre-randomization than the NPH (290.69 ± 82.31 vs. 246.04 ± 41.76 mg/dL, P = 0.021). The percentage of time with glucose between 80 and 180 mg/dL was 45.88 ± 27.04% in the IG and 53.56 ± 22.89% in the NPH (P = 0.341) and the percentage of glucose reduction was 31.47 ± 17.52% in the IG and 27.28 ± 14.56% in the NPH (P = 0.374). The percentage of time with glucose < 60 mg/dL was 0.14 ± 0.49% in the IG and 0.47 ± 1.74% in the NPH. Poststroke outcomes were not significantly different. In conclusion, IG is safe and equally effective as an NPH-based basal-bolus regimen for acute stroke patients with hyperglycemia receiving intensive care.Trial registration ClinicalTrials.gov, NCT02607943. Registered 18/11/2015, https://clinicaltrials.gov/ct2/show/NCT02607943 .

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Glucose; Critical Care; Female; Humans; Hypoglycemia; Insulin Glargine; Male; Middle Aged; Pilot Projects; Stroke

To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes.. We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.9─10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels.. At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed.. Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Risk Factors

To further investigate glycaemic control and hypoglycaemia in BRIGHT, focusing on the titration period.. BRIGHT was a multicentre, open-label, randomized, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve patients with uncontrolled type 2 diabetes initiated on glargine 300 U/mL (Gla-300) (N = 466) or degludec (IDeg-100) (N = 463). Predefined efficacy and safety outcomes were investigated during the initial 12-week titration period. In addition, patients' characteristics and clinical outcomes were assessed descriptively, stratified by confirmed (≤3.9 mmol/L) hypoglycaemia incidence during the initial titration period.. At week 12, HbA1c was comparable between Gla-300 (7.32%) and IDeg-100 (7.23%), with similar least squares (LS) mean reductions from baseline (-1.37% and - 1.39%, respectively; LS mean difference of 0.02; 95% confidence interval: -0.08 to 0.12). Patients who experienced hypoglycaemia during the initial titration period had numerically greater HbA1c reductions by week 12 than patients who did not (-1.46% vs. -1.28%), and higher incidence of anytime (24 hours; 73.3% vs. 35.7%) and nocturnal (00:00-06:00 hours; 30.0% vs. 11.9%) hypoglycaemia between weeks 13-24.. The use of Gla-300 resulted in similar glycaemic control as IDeg-100 during the initial 12-week titration period of the BRIGHT study, when less anytime (24 hours) hypoglycaemia with Gla-300 versus IDeg-100 has been reported. Experiencing hypoglycaemia shortly after initiating Gla-300 or IDeg-100 may be associated with hypoglycaemia incidence in the longer term, potentially impacting glycaemic management.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Effective glycemic control can reduce the risk of complications and their related costs in patients with type 2 diabetes (T2D). Many patients fail to reach hemoglobin A1c (HbA1c) ≤ 6.5% or < 7.0%, often due to adverse effects of treatment, such as hypoglycemia and weight gain. Glycemic targets should be individualized and consider multiple factors, including the risk of adverse events and the patient's characteristics and comorbid conditions.. To compare the odds and annual cost of achieving treatment targets, which incorporate HbA1c targets of < 7.5%, < 8.0%, and ≤ 9.0%, with insulin degludec/liraglutide (IDegLira) versus basal insulin and basal-bolus therapy.. This is a post hoc analysis of the DUAL V and DUAL VII 26-week trials, which randomized patients with T2D uncontrolled (HbA1c 7%-10%) on insulin glargine 100 units/mL (IGlar U100) and metformin to IDegLira or continued IGlar U100 titration (DUAL V) or IGlar U100 + insulin aspart (DUAL VII), all with metformin. Proportions of patients achieving HbA1c targets (< 7.5%, < 8.0%, and ≤ 9.0%) by the end of trial were assessed via 3 outcomes: alone, without either hypoglycemia or weight gain (double composite outcome), or without a combination of hypoglycemia and weight gain (triple composite outcome). The cost per patient achieving the triple composite outcome at each HbA1c target (< 7.5%, < 8.0%, and ≤ 9.0%) was calculated by dividing the annual cost of treatment by the proportion of patients achieving the target. This short-term (1-year) cost-effectiveness analysis was conducted from the perspective of a U.S. health care payer.. More patients achieved HbA1c < 7.5% (. Based on data from DUAL V and DUAL VII, this analysis showed that a greater or similar proportion of patients with T2D reached HbA1c targets with IDegLira compared with IGlar U100/basal-bolus therapy. Odds of achieving double or triple composite outcomes of HbA1c reduction without hypoglycemia and/or without weight gain were greatest for IDegLira. Short-term cost analyses based on the triple composite outcomes suggest that IDegLira is a cost-effective treatment option in the United States compared with either uptitration of IGlar U100 or basal-bolus therapy.. This study was supported by Novo Nordisk A/S. The analysis was based on the DUAL V (NCT01952145) and DUAL VII (NCT02420262) trials, which were funded and conducted by Novo Nordisk. This post hoc analysis was conceived and interpreted by the authors and drafted with medical writing support that was funded by Novo Nordisk. Novo Nordisk also reviewed the manuscript for medical accuracy. Hunt and Malkin are employees of Ossian Health Economics and Communications, which received consulting fees from Novo Nordisk during the conduct of this study and has received consulting fees from Novo Nordisk, unrelated to this study. Mocarski, Ranthe, and Schiffman are employees of Novo Nordisk and Novo Nordisk A/S. Cannon has received speaker fees/honoraria from Abbvie, Amgen, and Janssen; speaker fees from Novo Nordisk; and has stock ownership in Novo Nordisk. Bargiota has received speaker fees/honoraria from AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi, Boehringer Ingelheim, and Novartis. Billings has received personal fees from Novo Nordisk, Sanofi, and Dexcom, unrelated to this study. Leiter reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, and GSK, unrelated to this study. Doshi has no relevant conflicts of interest to disclose. Parts of this study were presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Topics: Adult; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Metformin; United States

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Parenteral Nutrition, Total; Prospective Studies; Risk Factors

To determine the early benefit:risk balance of dulaglutide versus insulin glargine in patients with type 2 diabetes mellitus (T2DM).. This post hoc analysis used data from a randomized, open-label study (AWARD-2; modified intention-to-treat group) in which suboptimally controlled metformin + glimepiride-treated patients received dulaglutide 1.5 mg (n = 273) or insulin glargine (n = 262). Two composite endpoints were used: for weeks 2-20, fasting serum glucose (FSG) <130 mg/dL (<7.2 mmol/L) without hypoglycemia (blood glucose ≤70 mg/dL [≤3.9 mmol/L] or severe hypoglycemia); at week 26, patients with glycated hemoglobin (HbA1c) <7.0% (<53.0 mmol/mol) or reduction from baseline ≥1.0% (≥10.9 mmol/mol), no hypoglycemia (as defined above) and no weight gain. Odds ratios (ORs) were generated using logistic regression analysis.. The probability of reaching the FSG target without hypoglycemia was higher with dulaglutide than with insulin glargine at weeks 4 (OR 1.78; 95% confidence interval [CI] 1.22-2.60) and 8 (OR 1.69; 95% CI 1.15-2.48). The proportion of patients achieving the 26-week endpoint was higher with dulaglutide (37.4% vs. 10.3%; OR 5.28; 95% CI 3.28-8.48).. Dulaglutide's balanced efficacy-to-safety profile compares favorably with that of insulin glargine and is apparent soon after treatment initiation and after 6 months of therapy.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin Glargine; Recombinant Fusion Proteins

This study aimed to evaluate the short-term cost-effectiveness of insulin degludec 200 units/mL (degludec) versus insulin glargine 300 units/mL (glargine U300) from a Dutch societal perspective.. A previously published model estimated costs [2018 euros (EUR)] and effectiveness [quality-adjusted life years (QALYs)] with degludec compared with glargine U300 over a 1-year time horizon. The model captured hypoglycaemia rates and insulin dosing. Clinical outcomes were informed by CONCLUDE (NCT03078478), a head-to-head randomised controlled trial in insulin-experienced patients with type 2 diabetes.. Treatment with degludec was associated with mean annual cost savings (EUR 24.71 per patient) relative to glargine U300, driven by a lower basal insulin dose and lower severe hypoglycaemia rate with degludec compared with glargine U300. Lower rates of non-severe nocturnal and severe hypoglycaemia resulted in improved effectiveness (+ 0.0045 QALYs) with degludec relative to glargine U300. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes.. This short-term analysis, informed by the latest clinical trial evidence, demonstrated that degludec was a cost-effective treatment option relative to glargine U300. As such, our modelling analysis suggests that degludec would represent an efficient use of Dutch public healthcare resources in this patient population.

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Ethnicity; Female; Health Expenditures; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Models, Econometric; Netherlands; Quality-Adjusted Life Years

To compare efficacy and safety of insulin glargine 300 units/mL (Gla-300) and 100 units/mL (Gla-100) in children and adolescents (6-17 years old) with type 1 diabetes.. EDITION JUNIOR was a noninferiority, international, open-label, two-arm, parallel-group, phase 3b trial. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to achieve fasting self-monitored plasma glucose levels of 90-130 mg/dL (5.0-7.2 mmol/L), with continuation of prior prandial insulin. The primary end point was change in HbA. Gla-300 provided similar glycemic control and safety profiles to Gla-100 in children and adolescents with type 1 diabetes, indicating that Gla-300 is a suitable therapeutic option in this population.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Equivalence Trials as Topic; Fasting; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Male

To report the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) versus standard-of-care basal insulin analogues (SOC-BI) at 12 months in the ACHIEVE Control trial, which is a prospective pragmatic randomized real-life study in insulin-naïve adults with type 2 diabetes (T2D).. A total of 3304 insulin-naïve adults with T2D and glycated haemoglobin (HbA1c) concentration of 64 to 97 mmol/mol (8.0% to 11.0%) after ≥1 year of treatment with two or more antihyperglycaemic agents were randomized to Gla-300 or SOC-BI. Key secondary endpoints included HbA1c target attainment without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at 12 months.. At 12 months, 26.1% (Gla-300) and 23.7% (SOC-BI) of adults achieved HbA1c targets without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.97-1.35); 33.0% and 29.5%, respectively, achieved HbA1c targets without documented symptomatic (<3.0 mmol/L [<54 mg/dL]) or severe hypoglycaemia (OR 1.19, 95% CI 1.02-1.38). The OR for HbA1c target achievement was 1.15 (95% CI 0.99-1.34), and favoured Gla-300 versus SOC-BI for absence of documented symptomatic or severe hypoglycaemia at 12 months for both ≤3.9 mmol/L (≤70 mg/dL; OR 1.21, 95% CI 1.05-1.40) and < 3.0 mmol/L (<54 mg/dL; OR 1.26, 95% CI 1.07-1.48).. Gla-300 tended to be associated with lower hypoglycaemia risk than SOC-BI in real-world clinical practice during the 12-month follow-up.

Topics: Adult; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Prospective Studies

FPG GOAL was a 24-week, open-label, treat-to-target randomized controlled trial which demonstrated that the optimal self-monitored fasting blood glucose (SM-FBG) target for most Chinese individuals with type 2 diabetes (T2D) using insulin glargine 100 IU/mL was 3.9-6.1 mmol/L. Individuals who achieved lower fasting plasma glucose (FPG) levels might achieve the target HbA1c of < 7% without increasing the risk of hypoglycemia.. For this post hoc analysis, individuals were redivided into three groups based on their actual laboratory FPG levels at 24 weeks: level 1, ≤ 5.6 mmol/L; level 2, > 5.6 to ≤ 6.1 mmol/L; and level 3, > 6.1 to ≤ 7.0 mmol/L.. At week 24, 863 individuals with diabetes had available FPG data and 179, 122, and 179 individuals achieved FPG levels 1, 2, and 3, respectively. The proportion of individuals with HbA1c < 7% or HbA1c < 7% without hypoglycemia (≤ 3.9 or ≤ 3.0 mmol/L) was significantly higher in FPG levels 1 (p < 0.01) and 2 (p < 0.05) than in level 3. The least squares mean changes from baseline in HbA1c (- 1.77% and - 1.66% vs - 1.34%; both p < 0.001) and 2-h postprandial glucose (- 3.88 mmol/L and - 3.98 mmol/L vs - 3.22 mmol/L; both p < 0.05) were also significantly higher in FPG levels 1 and 2 compared with level 3. Linear regression analysis showed a moderate relationship between FPG and HbA1c levels at 24 weeks (r = 0.449).. Chinese individuals with T2D who achieved lower FPG levels with insulin glargine 100 IU/mL were more likely to achieve the recommended target HbA1c of < 7% compared with those with higher FPG levels. ClinicalTrials.gov identifier NCT02545842.

Topics: Adolescent; Adult; Aged; Asian People; Blood Glucose; Blood Glucose Self-Monitoring; China; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Postprandial Period; Treatment Outcome; Young Adult

To compare the safety and efficacy of insulin glargine 300 U/mL (Gla-300) versus first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) at 6 months.. In the 12-month, open-label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin-naïve adults with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) 64 to 97 mmol/mol (8.0%-11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla-300 or SOC-BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per Healthcare Effectiveness Data and Information Set (HEDIS) criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months.. Of 1651 and 1653 participants randomized to Gla-300 and SOC-BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19, 95% CI 1.01-1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups.. Among insulin-naïve adults with poorly controlled T2D, Gla-300 was associated with a statistically significantly higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (vs SOC-BI) in a real-life population managed in a usual-care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers and decision makers.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

It is thought that a reduction in the frequency of basal insulin injections might facilitate treatment acceptance and adherence among patients with type 2 diabetes. Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment of diabetes.. We conducted a 26-week, randomized, double-blind, double-dummy, phase 2 trial to investigate the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (glycated hemoglobin level, 7.0 to 9.5%) while taking metformin with or without a dipeptidyl peptidase 4 inhibitor. The primary end point was the change in glycated hemoglobin level from baseline to week 26. Safety end points, including episodes of hypoglycemia and insulin-related adverse events, were also evaluated.. A total of 247 participants were randomly assigned (1:1) to receive icodec or glargine. Baseline characteristics were similar in the two groups; the mean baseline glycated hemoglobin level was 8.09% in the icodec group and 7.96% in the glargine group. The estimated mean change from baseline in the glycated hemoglobin level was -1.33 percentage points in the icodec group and -1.15 percentage points in the glargine group, to estimated means of 6.69% and 6.87%, respectively, at week 26; the estimated between-group difference in the change from baseline was -0.18 percentage points (95% CI, -0.38 to 0.02, P = 0.08). The observed rates of hypoglycemia with severity of level 2 (blood glucose level, <54 mg per deciliter) or level 3 (severe cognitive impairment) were low (icodec group, 0.53 events per patient-year; glargine group, 0.46 events per patient-year; estimated rate ratio, 1.09; 95% CI, 0.45 to 2.65). There was no between-group difference in insulin-related key adverse events, and rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and no serious events were deemed to be related to the trial medications.. Once-weekly treatment with insulin icodec had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes. (Funded by Novo Nordisk; NN1436-4383 ClinicalTrials.gov number, NCT03751657.).

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged

Cardiovascular outcomes in clinical trials with type 2 diabetes mellitus (T2DM) patients have shown that glucagon-like peptide-1 receptor agonist can have a beneficial effect on the kidney. This trial aimed to assess the effects of exenatide on renal outcomes in patients with T2DM and diabetic kidney disease (DKD).. We performed a randomized parallel study encompassing 4 general hospitals. T2DM patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and macroalbuminuria, defined as 24-h urinary albumin excretion rate (UAER) >0.3 g/24 h were randomized 1:1 to receive exenatide twice daily plus insulin glargine (intervention group) or insulin lispro plus glargine (control group) for 24 weeks. The primary outcome was the UAER percentage change from the baseline after 24 weeks of intervention. The rates of hypoglycemia, adverse events (AEs), and change in eGFR during the follow-up were measured as safety outcomes.. Between March 2016 and April 2019, 92 patients were randomized and took at least 1 dose of the study drug. The mean age of the participants was 56 years. At baseline, the median UAER was 1,512.0 mg/24 h and mean eGFR was 70.4 mL/min/1.73 m2. After 24 weeks of treatment, the UAER percentage change was significantly lower in the intervention group than in the control group (p = 0.0255). Moreover, the body weight declined by 1.3 kg in the intervention group (the difference between the 2 groups was 2.7 kg, p = 0.0001). Compared to the control group, a lower frequency of hypoglycemia and more gastrointestinal AEs were observed in the intervention group.. Exenatide plus insulin glargine treatment for 24 weeks resulted in a reduction of albuminuria in T2DM patients with DKD.

Topics: Albuminuria; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Drug Therapy, Combination; Exenatide; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Treatment Outcome

Older people with type 2 diabetes (T2DM) are at an increased risk of hypoglycaemia and its consequences. However, efficacy and safety data for basal insulin therapy are limited in these individuals. This patient-level meta-analysis assessed the treatment effects of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with T2DM ≥ 65 years old.. Data were pooled for patients randomised to receive Gla-300 or Gla-100 in the Phase 3a, treat-to-target EDITION 1, 2 and 3 trials. Glycaemic efficacy, hypoglycaemia, changes in body weight and insulin dosage and adverse events were examined over 6 months' treatment with Gla-300 versus Gla-100 for participants aged ≥ 65 and < 65 years.. Gla-300 was associated with a reduced risk of nocturnal hypoglycaemia versus Gla-100, accompanied by comparable glycaemic improvement, for people aged ≥ 65 and < 65 years with T2DM.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged

Heart failure (HF) is a common cardiovascular complication of type 2 diabetes (T2D). This secondary analysis investigated baseline factors and treatment differences associated with risk of hospitalization for HF (hHF), and the possible association between severe hypoglycemia and hHF.. DEVOTE was a treat-to-target, double-blind cardiovascular outcomes trial in patients (n = 7637) with T2D and high cardiovascular risk randomized to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). The main endpoint of this secondary analysis was time to first hHF (standardized MedDRA Query definition). Severe hypoglycemia was adjudicated (American Diabetes Association definition). The main endpoint and the temporal association between severe hypoglycemia and hHF were analyzed with a Cox proportional hazards regression model. Predictors of time to first hHF were identified using baseline variables.. Overall, 372 (4.9%) patients experienced hHF (550 events). There was no significant difference in the risk of hHF between treatments (hazard ratio [HR] 0.88 [0.72;1.08]. In patients with T2D and high cardiovascular risk there were no treatment differences in terms of hHF. Prior HF was the strongest predictor of future hHF events, and there was an association between severe hypoglycemia and subsequent hHF. Further research should evaluate whether the risk of hHF can be modified by treatments aimed at reducing hypoglycemia. Trial Registration NCT01959529.

Topics: Aged; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Disease Progression; Double-Blind Method; Female; Heart Failure; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Admission; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Compared with glargine 100 U/mL (Gla100), glargine 300 U/mL (Gla300) and degludec (Deg) - the ultralong-acting insulins - reportedly have more stable effects and reduce the risk of hypoglycemia. Currently, they are considered to be the most useful basal insulins. The present study aimed to compare the efficacy and safety of Gla300 and Deg on glycemic control using continuous glucose monitoring.. In this single-center, open-label, parallel-group, two-period, cross-over study, 30 patients with type 2 diabetes were randomized to once-daily Gla300 followed by Deg with the same units (n = 15) or vice versa (n = 15). The primary end-points of this study were the mean percentage of time within the target glucose range of 70-180 mg/dL as efficacy and hypoglycemia of <70 mg/dL as safety indicators, as measured using continuous glucose monitoring during each treatment period.. The mean percentage of time within the target glucose range was not different between Gla300 and Deg (77.8 ± 19.2 vs 76.9 ± 18.3%, P = 0.848). However, the mean percentage of time of hypoglycemia with Gla300 was significantly lower than that of Deg (1.3 ± 2.7 vs 5.5 ± 6.4%, P = 0.002). In the secondary safety end-points, the mean percentage of time of severe hypoglycemia (<54 mg/dL) or nocturnal hypoglycemia with Gla300 was also significantly lower than that of Deg.. The present study showed the comparable efficacy of Gla300 and Deg on glycemic control; however, the risk of hypoglycemia was markedly lower for Gla300 than for Deg.

Topics: Aged; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Prognosis; Safety

To investigate efficacy, safety and usability of the GlucoTab system for glycaemic management using insulin glargine U300 in non-critically ill hospitalized patients with type 2 diabetes (T2D).. In this open, non-controlled single-arm pilot study, glycaemic control at the general ward of a tertiary care hospital was guided by a mobile decision support system (GlucoTab) for basal-bolus insulin dosing using the novel basal insulin analogue insulin glargine U300 for the first time. Glycaemic control was surveilled with capillary glucose measurements and continuous glucose monitoring (CGM). The primary endpoint was efficacy of glycaemic management, defined as the percentage of blood glucose measurements within the target range of 3.9 to 7.8 mmol/L.. Treatment with GlucoTab using insulin glargine U300 in hospitalized patients with T2D is effective and safe.

Topics: Aged; Algorithms; Blood Glucose; Blood Glucose Self-Monitoring; Decision Support Techniques; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Female; Hospitalization; Humans; Hypoglycemia; Insulin Glargine; Insulin Infusion Systems; Male; Middle Aged; Mobile Applications; Pilot Projects; Risk Factors

To compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine.. Eligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP-4 inhibitors and sulphonylureas) and stabilized during a run-in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L.. A total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and -20.5 mmol/mol (-1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and -15.5 mmol/mol (-1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was -5.0 mmol/mol (-0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups.. When initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. ClinicalTrials.gov Identifier: NCT02738879.

Topics: Aged; Deprescriptions; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Least-Squares Analysis; Male; Metformin; Middle Aged; Sitagliptin Phosphate; Treatment Outcome

Basal insulin therapy often involves a compromise between achievement of glycaemic targets and avoidance of hypoglycaemia, dependent on how intensively insulin is titrated. In the Phase 3a EDITION 1, 2 and 3 studies, insulin glargine 300 U/mL (Gla-300) provided glycaemic control equivalent to that of insulin glargine 100 U/mL (Gla-100), with less hypoglycaemia in individuals with type 2 diabetes mellitus (T2DM). The current study evaluated the rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia over six months of treatment with Gla-300 or Gla-100 in the EDITION studies, as a function of HbA1c. Analysis was performed on patient-level data pooled from the three EDITION studies, and annualized hypoglycaemia rate as a function of HbA1c at Month 6 was fitted using a negative binomial regression model. Participants treated with Gla-300 experienced a consistently lower rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia as compared with those treated with Gla-100, regardless of HbA1c at Month 6. Results suggest that treatment with Gla-300 vs Gla-100 could allow individuals with T2DM to achieve equivalent glycaemic control with less hypoglycaemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Glargine; Intention to Treat Analysis; Male; Metformin; Middle Aged; Young Adult

Maintaining optimal glycaemic control reduces the risk of micro- and macrovascular complications in patients with type 2 diabetes. Typically, glycaemic control is based on glycated haemoglobin (HbA1c) as a measure of mean glucose concentration; however, this marker does not accurately reflect glycaemic variability (GV), which is characterized by the amplitude, frequency and duration of hypo- and hyperglycaemic fluctuations. In the present study, we analysed data from the LixiLan-O trial, which compared iGlarLixi, a titratable fixed-ratio combination of the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi) and long-acting basal insulin glargine 100 units/mL (iGlar), with its individual components, and the LixiLan-L trial, which compared iGlarLixi with iGlar. The GV features that were measured were mean and SD of self-measured plasma glucose (SMPG), high blood glucose index (HBGI) and low blood glucose index, area under the SMPG curve for each patient (AUCn), mean absolute glucose (MAG) and mean amplitude of glycaemic excursions (MAGE). By week 30, iGlarLixi improved all GV markers from baseline, with no increased hypoglycaemia risk. Significant improvements were observed in SMPG, SD of SMPG, HBGI, AUCn, MAG and MAGE compared with iGlar, and in SMPG, HBGI and AUCn, compared with Lixi.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Glargine; Male; Middle Aged; Peptides; Retrospective Studies

Epidemiological studies have reported a relationship between severe hypoglycemia, cognitive dysfunction, and dementia in middle-aged and older people with type 2 diabetes. However, whether severe or nonsevere hypoglycemia precedes cognitive dysfunction is unclear. Thus, the aim of this study was to analyze the relationship between hypoglycemia and incident cognitive dysfunction in a group of carefully followed patients using prospectively collected data in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial.. This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia who had additional cardiovascular risk factors and a Mini-Mental State Examination (MMSE) score ≥24 (. This analysis did not demonstrate an association between severe hypoglycemia and incident cognitive impairment either before (hazard ratio [HR] 1.16; 95% CI 0.89, 1.52) or after (HR 1.00; 95% CI 0.76, 1.31) adjusting for the severe hypoglycemia propensities. Conversely, nonsevere hypoglycemia was inversely related to incident cognitive impairment both before (HR 0.59; 95% CI 0.52, 0.68) and after (HR 0.58; 95% CI 0.51, 0.67) adjustment.. Hypoglycemia did not increase the risk of incident cognitive dysfunction in 11,495 middle-aged individuals with dysglycemia.

Topics: Aged; Cardiovascular Diseases; Cognitive Dysfunction; Educational Status; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Male; Metformin; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors

To confirm non-inferiority of insulin degludec/insulin aspart (IDegAsp) once-daily (OD) versus insulin glargine (IGlar) U100 OD + insulin aspart (IAsp) OD for HbA. A 38-week, randomised, open-label, treat-to-target (HbA. For W0-W26, mean percentage-change (standard deviation) HbA. IDegAsp OD/BID are effective treatment intensification options versus multiple injection basal-bolus therapies, achieving similar glycaemic control, with significantly less nocturnal hypoglycaemia.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Male; Middle Aged

The use of incretin-based therapy, rather than or complementary to, insulin therapy is an active area of research in hospitalized patients with type 2 diabetes (T2D). We determined the glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in hospitalized surgical patients with T2D.. This prospective open-label multicentre study randomized T2D patients undergoing non-cardiac surgery with admission blood glucose (BG) of 7.8 to 22.2 mmol/L who were under treatment with diet, oral agents or total insulin dose (TDD) ≤ 0.5 units/kg/day to either linagliptin (n = 128) daily or basal-bolus (n = 122) with glargine once daily and rapid-acting insulin before meals. Both groups received supplemental insulin for BG > 7.8 mmol/L. The primary endpoint was difference in mean daily BG between groups.. Mean daily BG was higher in the linagliptin group compared to the basal-bolus group (9.5 ± 2.6 vs 8.8 ± 2.3 mmol/L/dL, P = 0.03) with a mean daily BG difference of 0.6 mmol/L (95% confidence interval 0.04, 1.2). In patients with randomization BG < 11.1 mmol/L (63% of cohort), mean daily BG was similar in the linagliptin and basal-bolus groups (8.9 ± 2.3 vs 8.7 ± 2.3 mmol/L, P = 0.43); however, patients with BG ≥ 11.1 mmol/L who were treated with linagliptin had higher BG compared to the basal-bolus group (10.9 ± 2.6 vs 9.2 ± 2.2 mmol/L, P < 0.001). Linagliptin resulted in fewer hypoglycaemic events (1.6% vs 11%, P = 0.001; 86% relative risk reduction), with similar supplemental insulin and fewer daily insulin injections (2.0 ± 3.3 vs 3.1 ± 3.3, P < 0.001) compared to the basal-bolus group.. For patients with T2D undergoing non-cardiac surgery who presented with mild to moderate hyperglycaemia (BG < 11.1 mmol/L), daily linagliptin is a safe and effective alternative to multi-dose insulin therapy, resulting in similar glucose control with lower hypoglycaemia.

Topics: Aged; Amputation, Surgical; Blood Glucose; Diabetes Mellitus, Type 2; Digestive System Surgical Procedures; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Gynecologic Surgical Procedures; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Short-Acting; Linagliptin; Male; Middle Aged; Orthopedic Procedures; Perioperative Care; Surgical Procedures, Operative; Treatment Outcome; Urologic Surgical Procedures

Because of its physico-chemical properties, insulin glargine is usually not mixable with rapid insulins. BioChaperone BC147 is a polyanionic amphiphilic polymer, solubilizing insulin glargine at neutral pH, and thus enabling stable glargine formulation with fast-acting insulin lispro (BioChaperone glargine lispro co-formulation [BC Combo]). We investigated pharmacokinetic (PK) endpoints and postprandial glucose (PPG) control after administration of BC Combo (75% insulin glargine, 25% insulin lispro), insulin lispro Mix25 (LMix) and separate injections of insulins glargine (75% total dose) and lispro (25% total dose [G + L]) immediately before ingestion of a mixed meal in people with type 2 diabetes mellitus (T2DM), using a randomized, double-blind, double-dummy crossover study design. Participants received individualized bolus doses (mean 0.62 U/kg) of BC Combo, LMix or G + L, together with a solid mixed meal (610 kcal, 50% carbohydrate, 30% fat, 20% protein). Insulin dosages were kept constant for each study day. Thirty-nine participants with T2DM (mean ± SD age and glycated haemoglobin 60.8 ± 7.5 years and  64 ± 6 mmol/mol, respectively) were randomized. BC Combo improved the predefined primary endpoint, early PPG control, compared to LMix (incremental area under the blood glucose concentration-time curve from 0 to 2 hours after the meal [ΔAUC

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Male; Middle Aged; Postprandial Period; Young Adult

The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older.. A total of 7637 patients in the DEVOTE trial, a treat-to-target, randomized, double-blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50-64 years, n = 3682; 65-74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all-cause mortality, severe hypoglycaemia and serious adverse events (SAEs).. Patients with increasing age had higher risks of CV death, all-cause mortality and SAEs, and there were non-significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all-cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non-significant interactions between treatment and age with regard to these outcomes.. There were higher risks of CV death, all-cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all-cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all-cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

To compare the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL (Gla-300) in people with inadequately controlled type 2 diabetes.. Take Control (EudraCT number: 2015-001626-42) was a 24-week, multi-national, open-label, controlled, two-arm, parallel-group study in insulin-naïve and pre-treated participants, randomized 1:1 to a self- or physician-managed titration of Gla-300. The fasting self-monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant-reported outcomes (PROs).. At week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self- and physician-managed groups, respectively, with an LS mean difference of -0.13% [95% confidence interval -0.2619 to -0.0004] (-1.4 mmol/mol [-2.863 to -0.004]), demonstrating non-inferiority (P < 0.0001) and superiority (P = 0.0247) of self- versus physician-managed titration. Significantly more of the self- than physician-managed group achieved SMPG target without hypoglycaemia (67% vs 58%; P = 0.0187). Overall, hypoglycaemia incidence was similar in each group. No safety concerns were reported. In both groups, similar PRO improvements were observed for distress related to diabetes disease burden and for confidence in diabetes self-management, with even more individuals achieving a clinically relevant reduction in emotional burden and fewer individuals with high emotional burden in the self-managed group.. Self-managed titration of Gla-300 was superior to physician-managed titration in terms of HbA1c reduction, accompanied by similar total PRO scores, with a clinically relevant reduction in emotional burden, and similar hypoglycaemia frequency.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Self-Management

We compared the efficacy and safety of insulin degludec/aspart (IDegAsp) twice-daily injections with insulin glargine 300 U/mL and insulin glulisine basal-bolus therapy (Gla300/Glu) using insulin glargine 300 U/mL (Gla300) and insulin glulisine (Glu).. A total of 20 patients with type 2 diabetes mellitus were treated with IDegAsp twice-daily injections; achievement of target preprandial glucose concentration of 100-130 mg/dL at breakfast and supper was determined using a wearable flash glucose monitoring system. Patients were later switched to Gla300/Glu basal-bolus therapy before breakfast and before supper. Data were collected on days 2-4 and days 12-14 for each treatment period. The study's primary efficacy end-point was the mean percentage of time with a target glucose range of 70-180 mg/dL, and safety end-points were the mean percentage of time with hypoglycemia having glucose levels <70 mg/dL, clinically important hypoglycemia with glucose levels <54 mg/dL and nocturnal (00.00-06.00) hypoglycemia.. Considering efficacy, the mean percentage of time for the target glucose range of IDegAsp was significantly lower than that of Gla300/Glu (73.1 [69.4-81.1] vs 84.2 [80.2-93.1], P = 0.001). Considering safety, the mean percentages of hypoglycemia (<70 mg/dL; 2.1 [0.0-9.4] vs 14.4 [4.4-22.3]), clinically important hypoglycemia (<54 mg/dL; 0.0 [0.0-0.2] vs 1.9 [0.0-5.6]) and nocturnal (00.00-06.00 hours) hypoglycemia (0.5 [0.0-5.9] vs 8.9 [3.1-11.8]) of Gla300/Glu were significantly lower than those of IDegAsp (P = 0.012, 0.036 and 0.007, respectively).. When compared with the IDegAsp twice-daily injections, Gla300/Glu basal-bolus therapy might achieve more effective glycemic control without hypoglycemic risk.

Topics: Aged; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Patient Safety; Prognosis

This study aimed to investigate the safety of insulin degludec (degludec) in relation to age and risk of hypoglycaemia post hoc in individuals with type 2 diabetes (T2D) (SWITCH 2 trial).. In this crossover study, individuals with T2D who were at risk of hypoglycaemia were randomized to double-blind treatment with degludec or insulin glargine 100 units/mL (glargine U100) ± oral antidiabetic drugs. After 32 weeks, patients crossed over to the other treatment. Primary endpoint was number of overall severe (positively adjudicated) or glucose-confirmed (plasma glucose <56 mg/dL; 3.1 mmol/L) symptomatic hypoglycaemia events during the two 16-week maintenance periods.. Treatment with degludec was safe and effective, with a frequency of hypoglycaemia lower than that with glargine U100 in both younger and older individuals (>65 years) with T2D.

Topics: Adult; Aged; Aged, 80 and over; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Young Adult

The optimal fasting blood glucose (FBG) target of achieving HbA1c less than 7.0% in type 2 diabetes (T2D) patients remains controversial. This open-label trial randomized (1:3:3) 947 adults with uncontrolled T2D (HbA1c >7% to ≤10.5%) who were using one to three oral antidiabetic drugs to achieve an FBG target of 3.9 < FBG ≤5.6 mmol/L (Group 1), 3.9 < FBG ≤6.1 mmol/L (Group 2) or of 3.9 < FBG ≤7.0 mmol/L (Group 3). Targets were achieved using a pre-defined insulin glargine 100 U/mL titration scheme. The primary endpoint was proportion of patients achieving HbA1c <7.0% at 24 weeks. At 24 weeks, 44.4%, 46.1% and 37.7% of patients achieved HbA1c <7.0% in Groups 1, 2 and 3, respectively (P = 0.017; Group 2 vs Group 3). Alert hypoglycaemia (glucose ≤3.9 mmol/L) was significantly more frequent in Group 1 than in Group 3 (38.9 vs 23.3%; P < 0.001) but was not in Group 2 vs Group 3 (27.5% vs 23.3%; P = 0.177). Clinically important hypoglycaemia (glucose ≤3.0 mmol/L) was reported in 4.8%, 2.0% and 3.8% of patients in Groups 1, 2 and 3, respectively. In conclusion, the optimal FBG target for most Chinese patients with T2D appears to be 3.9-6.1 mmol/L.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Goals; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Reference Values; Treatment Outcome

A head-to-head trial (NCT03078478) between insulin degludec and insulin glargine U300 with the primary objective of comparing the risk of hypoglycemia is being conducted. During trial conduct, safety concerns related to the glycemic data collection system led to a postinitiation protocol amendment, described here.. This randomized (1:1), open-label, treat-to-target, multinational trial was initiated in March 2017 with a planned treatment period of 52 weeks (16 weeks titration + 36 weeks maintenance). Overall, ~1600 insulin-experienced patients at risk of developing hypoglycemia based on predefined risk factors were included. The protocol amendment implemented in February 2018 resulted in assuring patient safety and an extension of the total treatment period up to 88 weeks (16 weeks titration + variable maintenance 1 + 36 weeks maintenance 2). The original glycemic data collection system (MyGlucoHealth blood glucose meter + electronic diary) was discontinued because of safety concerns and replaced with an Abbott blood glucose meter and paper diary to collect self-measured blood glucose and hypoglycemic episodes. The primary endpoint of number of severe or blood-glucose confirmed symptomatic hypoglycemic episodes will be evaluated with the same analysis duration and statistical methods as the original protocol. Only relevant changes were implemented to maintain patient safety while permitting evaluation of the scientific objectives of the trial.. These observations highlight the importance of safety surveillance during trial conduct despite the use of currently marketed glucose monitoring devices. The prompt protocol amendment and ensuing actions ensured that the scientific integrity of the trial was not compromised.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Glucose Self-Monitoring; Chemotherapy, Adjuvant; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemia; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Research Design; Treatment Outcome; Young Adult

Video abstract: View a video abstract for this article.. This multicentre (N = 104), randomized controlled phase 4 study compared the efficacy and safety of insulin glargine 300 units/mL (Gla-300) with insulin glargine 100 units/mL (Gla-100) in patients with type 1 diabetes (T1D).. Patients were randomized 1:1 to self-perform morning Gla-300 or Gla-100 injections daily for 16 weeks. The primary endpoint was percentage of time blood glucose remained in the target range (70-180 mg/dL) during Week 15/16, measured by blinded continuous glucose monitoring. Secondary endpoints included incidence and rate of nocturnal symptomatic hypoglycaemia (≤70 mg/dL), glycaemic variability parameters and safety assessments. Exploratory analyses were performed in patients with glycated haemoglobin (HbA1c) <7.5% at Week 16.. Overall, 638 patients with T1D were included (Gla-300, n = 320; Gla-100, n = 318). In the modified intent-to-treat (mITT) population, no differences between Gla-300 and Gla-100 were observed in time in range, in glycaemic variability, or in incidence or rates of nocturnal symptomatic hypoglycaemia. In exploratory analyses of patients with HbA1c <7.5% at Week 16, Gla-300 recipients had greater improvement in time in range over 24 hours, during the day and at night compared with Gla-100 recipients (P < 0.05), with small increases in overall hypoglycaemia.. Time in range and glycaemic variability were similar for Gla-300 and Gla-100 recipients at the end of study in the mITT population of relatively well-controlled patients with T1D. In patients with end-of-study HbA1c <7.5%, exploratory analyses suggested that Gla-300 provided improvements in time in range compared with Gla-100.

Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Injections; Insulin Glargine; Intention to Treat Analysis; Male; Middle Aged; Time Factors; Treatment Outcome

Lilly insulin glargine (LY IGlar; Basaglar. Patients from India and East Asia (Korea and Taiwan) with T2DM who were insulin naïve (glycated hemoglobin (HbA1c) ≥ 7.0% and ≤ 11.0%) or on basal insulin (HbA1c ≤ 11.0%) were randomized to receive LY IGlar or IGlar along with oral antihyperglycemic medications (OAMs) for 24 weeks. Patients were instructed to self-titrate from the starting dose by 1 unit/day until fasting blood glucose (FBG) ≤ 5.6 mmol/L (100 mg/dL) was achieved. The key outcome was HbA1c change from baseline to Week 24.. Within-group least-squares mean (LSM) decrease (baseline to Week 24) in HbA1c was similar between treatments. The upper limit of confidence interval (CI) for treatment difference was below the defined 0.4% noninferiority margin in India (LY IGlar: - 0.83%; IGlar: - 0.62%; difference [95% CI] - 0.21 [- 0.70, 0.28]) and East Asia (LY IGlar: - 1.28%; IGlar: - 1.26%; difference [95% CI] - 0.02 [- 0.34, 0.30]) subpopulations. Results of other efficacy and safety endpoints at Week 24 were similar between treatments in both subpopulations. LSM self-monitored FBG levels were similar between treatments at all visits in both subpopulations except at Week 24 in the India subpopulation (LY IGlar: 5.65 [0.10] mmol/L or 101.8 [1.86] mg/dL; IGlar: 5.18 [0.10] mmol/L or 93.3 [1.75] mg/dL; p = 0.002).. Efficacy and safety profiles of LY IGlar and IGlar, in combination with OAMs, were similar in India and East Asia subpopulations. This was consistent with the ELEMENT 5 total population.. NCT02302716.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin; Insulin Glargine; Male; Middle Aged; Prospective Studies; Republic of Korea; Taiwan

In this post hoc analysis of the randomized controlled LixiLan-O trial in insulin-naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed-ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Least-Squares Analysis; Male; Middle Aged; Peptides; Treatment Outcome; Weight Gain

We evaluated risk factors for clinically relevant hypoglycaemia (blood glucose <3 mmol/L) in patients with type 2 diabetes during insulin glargine self-titration. Data were from two clinical trials in which patients were able to improve glycaemic control by self-titration of insulin glargine using a simple algorithm.. We performed post hoc analyses of pooled treatment groups from each of two Phase 3 studies comparing LY2963016 with LANTUS: ELEMENT-2 (double-blind) and ELEMENT-5 (open label). Clinically relevant hypoglycaemia was analysed by category of HbA1c (<7%, 7%-8.5%, >8.5%) at Week 12 (titration period) and at Week 24 (overall study), and by subgroups of age (<65, ≥65 years) and previous insulin use (naïve or not).. In the ELEMENT-2 study (N = 756), there were no overall differences in rate or incidence of hypoglycaemia among HbA1c categories. In the ELEMENT-5 study (N = 493), patients with HbA1c greater than 8.5% had a lower rate and incidence of hypoglycaemia throughout the study compared to those in the lower HbA1c categories. In both studies, patients 65 years of age or older, compared to those less than 65 years, had a higher rate and incidence of hypoglycaemia during the titration phase, had lower baseline HbA1c, and experienced smaller increases in dose, with no differences in HbA1c post baseline. The rate and incidence of hypoglycaemia was similar between naïve patients and patients previously using basal insulin, across all levels of glycaemic control. With the exception of the older subgroup, hypoglycaemia rates were similar during titration and maintenance periods.. Our results support broader use of self-titration algorithms for patients with type 2 diabetes.

Topics: Aged; Algorithms; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Male; Middle Aged; Self Care

The short-term efficacy and safety of insulin degludec U100 (IDeg) in patients with type 2 diabetes have not been reported widely. We compared insulin IDeg and insulin glargine U100 (IGla) for glycemic control and glucose variability in hospitalized patients with type 2 diabetes. In an open-label, multicenter, randomized controlled trial, 74 patients were randomly assigned to either the IDeg (36 patients) or IGla (38 patients) group and were administered with basal-bolus therapy during hospitalization. Following the start of the treatment, on day 11, glucose variability was assessed by continuous glucose monitoring. A fasting blood glucose level of 110 mg/dL and 2-hour postprandial blood glucose level of 180 mg/dL throughout at least one day during the observation period were achieved in 31.3% (10/32) and 30.6% (11/36) of the patients in the IDeg and IGla groups, respectively. The 6-point self-monitoring of blood glucose profiles showed a significant difference between the two groups. On day 7, the intra-day variation was larger in the IDeg group than in the IGla group. The incidence of hypoglycemia or glucose variability was comparable in the two groups. This study suggests that short-term efficacy and safety of IDeg and IGla in patients with type 2 diabetes during the initial phase of basal-bolus therapy were comparable, and these results can help in deciding which treatment to opt for.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Meals; Middle Aged; Postprandial Period; Treatment Outcome

Glycemic control in patients with chronic kidney disease (CKD) is particularly hard to achieve because of a slower insulin degradation by the kidney. It might modify the long-acting insulin analogue pharmacokinetics, increasing its time-action and the risk of hypoglycemia. However, because this insulin has no peak action, it might be a more tolerable approach to patients with CKD. This hypothesis remains to be tested, because no study has thus far examined the efficacy and safety profile of long-acting basal analogues in patients with significant loss of renal function. The purpose of this study was to compare the glycemic response to treatment with glargine U100 or neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus (T2DM) and CKD stages 3 and 4.. Our results found that insulin glargine U100 could be effective, once it improved glycemic control, reducing HbA

Topics: Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Renal Insufficiency, Chronic; Treatment Outcome

Topics: Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Combinations; Drug Monitoring; Drug Resistance, Multiple; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Metformin; Obesity; Overweight; Weight Gain; Weight Loss

Insulin glargine 300 U/mL (Gla-300) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL (Gla-100). We have compared these insulins over 1 year in people with type 1 diabetes (T1DM).. EDITION 4 was a 6-month, multicentre, randomized, open-label phase 3 study. People with T1DM who completed the 6 months continued randomized Gla-300 or Gla-100 once daily, morning or evening, for a further 6 months.. Among 549 participants randomized, 444 completed the 12-month study period (Gla-300, 80%; Gla-100, 82%). Mean HbA1c decreased similarly from baseline to month 12 in the 2 treatment groups (difference, 0.02 [95% CI, -0.13 to 0.17]) %-units [0.2 (-1.5 to 1.9) mmol/mol]), to a mean of 7.86 %-units (62.4 mmol/mol) in both groups. For morning vs evening injection, there was no difference in HbA1c change over 12 months for Gla-100, but a significantly larger decrease in HbA1c was observed in the Gla-300 morning group than in the Gla-300 evening group (difference, -0.25 [-0.47 to -0.04] %-units [-2.7 (-5.2 to -0.4) mmol/mol]). Mean glucose from the 8-point SMPG profiles decreased from baseline, and was similar between the 2 treatment groups. Basal insulin dose was 20% higher with Gla-300 than with Gla-100, while hypoglycaemia event rates, analysed at night, over 24 hours, or according to different glycaemic thresholds, did not differ between treatment groups, regardless of injection time. Adverse event profiles did not differ between groups.. In T1DM, Gla-300 provides glucose control comparable to that of Gla-100, and can be given at any time of day.

Topics: Activities of Daily Living; Adult; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Compounding; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Insulin Glargine; Intention to Treat Analysis; Male; Middle Aged; Osmolar Concentration; Overweight; Patient Dropouts; Quality of Life; Severity of Illness Index; Weight Gain

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin.

Topics: Administration, Oral; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Compounding; Drug Monitoring; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Intention to Treat Analysis; Osmolar Concentration; Severity of Illness Index

MK-1293 is an insulin glargine that has an amino acid sequence identical to that of Lantus, the originator insulin glargine. Two euglycaemic clamp studies, 1 in subjects with type 1 diabetes (T1D) and 1 in healthy subjects, were conducted to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity between MK-1293 and Lantus commercially procured in both the European Union (EU-Lantus) and the USA (US-Lantus).. Both studies were single-dose, randomized, double-blind, single-centre, crossover studies with ≥7 days between dosing periods. A 2-treatment, 4-period replicate crossover study in T1D subjects (N = 76) compared the PK and PD of MK-1293 to EU-Lantus for 30 hours after dosing. A 3-period crossover study in healthy subjects (N = 109) compared the PK and PD of MK-1293, EU-Lantus and US-Lantus for 24 hours after dosing. In both studies, all subjects received single 0.4 units/kg subcutaneous doses of MK-1293 or Lantus in all dosing periods. Pharmacokinetic assessment was based on LC-MS/MS-based measurement of the major insulin glargine metabolite (M1) and PD was characterized using the euglycaemic clamp platform.. In both studies, pre-specified similarity criteria were met between MK-1293 and Lantus for comparison of PK (AUC. Based on comparative assessment in both T1D and healthy subjects, it can be concluded that the PK and PD properties of MK-1293 are highly similar to those of Lantus. (ClinicalTrials.gov: NCT02059174).

Topics: Adult; Biosimilar Pharmaceuticals; Biotransformation; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; European Union; Female; Glucose Clamp Technique; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Patient Dropouts; United States; Young Adult

To test the hypothesis that, as well as lowering weight and increasing plasma triglyceride (TG) levels and hepatic fat compared with insulin glargine (GL) in patients with type 1 diabetes, the attenuated peripheral effects of basal insulin peglispro (BIL) may include increased free fatty acid flux to the liver, causing increased very-low-density lipoprotein (VLDL)-TG secretion and lipid oxidation, and decreased TG adipose tissue deposition.. In this open-label, randomized, 2-period crossover study, 14 patients with type 1 diabetes received once-daily, individualized, stable BIL or GL doses for 3 weeks. Palmitate flux was assessed using [9,10-. The VLDL-TG concentration and secretion rate, and palmitate flux were statistically significantly higher during BIL than during GL treatment (58%, 51% and 35%, respectively). The ratios of least squares (LS) geometric means for VLDL-TG clearance and oxidation were 0.92 (95% confidence interval [CI] 0.72, 1.17) and 1.31 (95% CI 0.91, 1.90), respectively. The difference in LS means for VLDL-TG storage rate was -0.36 (95% CI -0.83, 0.12).. BIL-treated patients had higher effective lipolysis, VLDL-TG secretion and VLDL-TG concentration compared with GL-treated patients, explaining the increased plasma TG concentrations reported previously. Data support attenuated effects of BIL on lipolysis, in addition to the recently described hepato-preferential glucodynamic effects.

Topics: Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypertriglyceridemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Lispro; Lipolysis; Lipoproteins, VLDL; Male; Middle Aged; Polyethylene Glycols; Triglycerides; Young Adult

The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality.. In DEVOTE, patients with type 2 diabetes were randomised to receive either insulin degludec or insulin glargine U100 (100 units/ml) once daily (between dinner and bedtime) in an event-driven, double-blind, treat-to-target cardiovascular outcomes trial. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE; cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In the present analysis, the associations of severe hypoglycaemia with both MACE and all-cause mortality was evaluated in the pooled trial population using time-to-event analyses, with severe hypoglycaemia as a time-dependent variable and randomised treatment as a fixed factor. An investigation with interaction terms indicated that the effect of severe hypoglycaemia on the risk of MACE and all-cause mortality were the same for both treatment arms, and so the temporal association for severe hypoglycaemia with subsequent MACE and all-cause mortality is reported for the pooled population.. There was a non-significant difference in the risk of MACE for individuals who had vs those who had not experienced severe hypoglycaemia during the trial (HR 1.38, 95% CI 0.96, 1.96; p = 0.080) and therefore there was no temporal relationship between severe hypoglycaemia and MACE. There was a significantly higher risk of all-cause mortality for patients who had vs those who had not experienced severe hypoglycaemia during the trial (HR 2.51, 95% CI 1.79, 3.50; p < 0.001). There was a higher risk of all-cause mortality 15, 30, 60, 90, 180 and 365 days after experiencing severe hypoglycaemia compared with not experiencing severe hypoglycaemia in the same time interval. The association between severe hypoglycaemia and all-cause mortality was maintained after adjustment for the following baseline characteristics: age, sex, HbA. The results from these analyses demonstrate an association between severe hypoglycaemia and all-cause mortality. Furthermore, they indicate that patients who experienced severe hypoglycaemia were particularly at greater risk of death in the short term after the hypoglycaemic episode. These findings indicate that severe hypoglycaemia is associated with higher subsequent mortality; however, they cannot answer the question as to whether severe hypoglycaemia serves as a risk marker for adverse outcomes or whether there is a direct causal effect.. ClinicalTrials.gov NCT01959529.

Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male

Assess efficacy, hypoglycemia, and weight gain in patients with type 2 diabetes (T2D) treated with insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) across different age groups.. Pooled data were generated for patients randomized to Gla-300 or Gla-100 in the EDITION 2 (NCT01499095) and 3 (NCT01676220) studies. In 4 age groups (<55, ≥55 to <60, ≥60 to <65, ≥65 years), glycated hemoglobin A1C (A1C), percentage of patients reaching A1C <7.5% (58 mmol/mol), weight change, confirmed hypoglycemia (blood glucose ≤70 mg/dL), and/or severe hypoglycemia (events requiring third-party assistance) were analyzed with descriptive statistics and logistic, binomial, and analysis of covariance regression modeling.. A1C reductions from baseline and proportions of patients at target were similar for Gla-300 and Gla-100 across all age groups at 6 and 12 months, but hypoglycemia incidence and event rate were lower with Gla-300 at 6 (both P<.001) and 12 months ( P<.001 and P = .005, respectively). Patients on Gla-300 gained less weight than those on Gla-100 at 6 ( P = .027) and 12 months ( P = .021). Changes in weight and daily weight-adjusted insulin dose decreased with increasing age at 6 ( P<.001 and P = .017, respectively) and 12 months ( P<.001 and P = .011, respectively).. Older patients with T2D may benefit from treatment with Gla-300, which is associated with a lower hypoglycemia rate and less weight gain with similar efficacy compared with Gla-100.. A1C = glycated hemoglobin A1C BMI = body mass index Gla-100 = insulin glargine 100 U/mL Gla-300 = insulin glargine 300 U/mL OAD = oral antidiabetes drug T2D = type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Aging; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypoglycemia; Incidence; Insulin Glargine; Male; Middle Aged; Weight Gain; Young Adult

To obtain estimates of the relative treatment effects between insulin degludec/liraglutide (IDegLira) and insulin glargine U100/lixisenatide (iGlarLixi) in patients with type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin therapy.. Data from phase 3 trials providing evidence for estimating the relative efficacy and safety of IDegLira vs iGlarLixi in patients uncontrolled on basal insulin-only regimens were used in this analysis. Outcomes of interest were changes in HbA. The assumptions made in the indirect comparison and differences between the included trials in baseline HbA. The results of this indirect treatment comparison demonstrate that, among patients with T2DM uncontrolled on basal insulin, treatment with IDegLira results in a greater reduction of HbA

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Middle Aged; Peptides; Weight Loss

To describe in type 2 diabetes the 24-hour distribution of hypoglycaemia and compare the frequency of nocturnal events based on a predefined nocturnal window or an expanded interval, using illustrative data for two insulin glargine formulations.. Temporal distribution of hypoglycaemic events was assessed descriptively and by profile using participant-level data from three randomized trials comparing insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100). Risk of hypoglycaemia and annualized event rates were compared for the predefined nocturnal interval (00:00 to 05:59h) and an expanded window (22:00h to the pre-breakfast glucose measurement).. Confirmed (≤3.9mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 06:00 and 10:00 h with both insulins. Nearly threefold more events were identified using the expanded nocturnal interval. Risk of ≥1 nocturnal event was 25% lower with Gla-300 than Gla-100 with the predefined, and 16% lower with the expanded interval; annualized event rates were 31% and 24% lower with the predefined and expanded window, respectively. The between-insulin difference in number of nocturnal events depended markedly on the chosen nocturnal interval (556 vs. 1145 fewer events with Gla-300 using the predefined vs. expanded interval).. The predefined 00:00-05:59h nocturnal interval excluded many hypoglycaemic events occurring during the actual overnight interval. While Gla-300 reduced hypoglycaemic events versus Gla-100 (regardless of the interval considered), the results obtained using the expanded window better reflect the clinical experience of people treated with basal insulin.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin Glargine; Male; Middle Aged; Time Factors

Safe and easily implemented treatment regimens are needed for the management of patients with type 2 diabetes mellitus (T2DM) in long-term care (LTC) and skilled nursing facilities.. This 6-month open-label randomized controlled trial compared the efficacy and safety of a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in LTC residents with T2DM.. Three LTC institutions affiliated with a community safety-net hospital, US Department of Veterans Affairs and Emory Healthcare System in Atlanta, Georgia.. A total of 140 residents with T2DM treated with oral antidiabetic agents or low-dose insulin (≤0.1 U/kg/d), with fasting or premeal blood glucose (BG) > 180 mg/dL and/or HbA1c >7.5%.. Baseline antidiabetic therapy, except metformin, was discontinued on trial entry. Residents were treated with linagliptin 5 mg/d (n = 67) or glargine at a starting dose of 0.1 U/kg/d (n = 73). Both groups received supplemental rapid-acting insulin before meals for BG > 200 mg/dL.. Primary outcome was mean difference in daily BG between groups. Main secondary endpoints included differences in frequency of hypoglycemia, glycosylated hemoglobin (HbA1c), complications, emergency department visits, and hospital transfers.. Treatment with linagliptin resulted in no significant differences in mean daily BG (146 ± 34 mg/dL vs. 157 ± 36 mg/dL, P = .07) compared to glargine. Linagliptin treatment resulted in fewer mild hypoglycemic events <70 mg/dL (3% vs. 37%, P < .001), but there were no differences in BG < 54 mg/dL (P = .06) or <40 mg/dL (P = .05) compared to glargine. There were no significant between-group differences in HbA1c, length of stay, complications, emergency department visits, or hospitalizations.. Treatment with linagliptin resulted in noninferior glycemic control and in significantly lower risk of hypoglycemia compared to insulin glargine in long-term care and skilled nursing facility residents with type 2 diabetes.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Linagliptin; Male; Residential Facilities; Skilled Nursing Facilities

To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine.. This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG < 130 mg/dL were randomized (1:1) to either arm A (no sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage.. A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08).. Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Intention to Treat Analysis; Lost to Follow-Up; Male; Meals; Middle Aged; Monitoring, Ambulatory; Patient Dropouts; Pilot Projects

To assess efficacy and safety of dulaglutide 1.5 mg combined with insulin, categorized by subgroups of baseline glycated haemoglobin (HbA1c; ≤9% and >9% [≤74.9 and >74.9 mmol/mol]), age (<65 and ≥65 years), and duration of diabetes (<10 and ≥10 years) at 6 months in patients with type 2 diabetes (T2D).. This pooled analysis was conducted in a population of patients with T2D with similar baseline characteristics who were included in the AWARD-4 and AWARD-9 clinical trials and randomized to dulaglutide 1.5 mg (pooled mean baseline age 59 years, duration of diabetes 13 years, HbA1c 8.4% [68.3 mmol/mol]). Weight and hypoglycaemia were analysed by individual trial. In AWARD-4, dulaglutide plus lispro three times daily was assessed against glargine plus lispro three times daily. In AWARD-9, dulaglutide added to glargine was assessed against placebo added to glargine. Insulins were titrated to target in both trials.. A total of 445 patients were included in this analysis (73% with HbA1c ≤9%, 27% [≤74.9 mmol/mol] with HbA1c >9% [>74.9 mmol/mol]; 70% aged <65 years, 30% aged ≥65 years; 36% with duration of diabetes <10 years, 64% with duration of diabetes ≥10 years). At 6 months, dulaglutide 1.5 mg significantly reduced HbA1c in all subgroups (P < .001), with the highest reduction observed in patients with baseline HbA1c >9% (>74.9 mmol/mol) (range - 1.3% to -2.5% [-14.2 to -27.3 mmol/mol]). The incidence rates of documented symptomatic and severe hypoglycaemia were similar in all subgroups in both trials. The most common adverse events observed in each trial were gastrointestinal in nature.. Dulaglutide 1.5 mg combined with basal or prandial insulin is efficacious for patients with T2D irrespective of age, duration of diabetes or baseline HbA1c.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin Glargine; Insulin Lispro; Male; Middle Aged; Recombinant Fusion Proteins; Treatment Outcome

To compare the efficacy and safety of adding the glucagon-like peptide-1 receptor agonist exenatide once weekly (QW) 2 mg or placebo among patients with type 2 diabetes who were inadequately controlled despite titrated insulin glargine (IG) ± metformin.. This multicentre, double-blind study (ClinicalTrials.gov identifier: NCT02229383) randomized (1:1) patients with persistent hyperglycaemia after an 8-week titration phase (glycated haemoglobin [HbA1c] 7.0%-10.5% [53-91 mmol/mol]) to exenatide QW or placebo. The primary endpoint was HbA1c change from baseline to week 28. Secondary endpoints included body weight, 2-hour postprandial glucose, and mean daily IG dose.. Of 464 randomized patients (mean: age, 58 years; HbA1c, 8.5% [69 mmol/mol]; diabetes duration, 11.3 years), 91% completed 28 weeks. Exenatide QW + IG vs placebo + IG significantly reduced HbA1c (least-squares mean difference, -0.73% [-8.0 mmol/mol]; 95% confidence interval, -0.93%, -0.53% [-10.2, -5.8 mmol/mol]; P < .001; final HbA1c, 7.55% [59 mmol/mol] and 8.24% [67 mmol/mol], respectively); body weight (-1.50 kg; -2.17, -0.84; P < .001); and 2-hour postprandial glucose (-1.52 mmol/L [-27.5 mg/dL]; -2.15, -0.90 [-38.7, -16.2]; P < .001). Significantly more exenatide QW + IG-treated patients vs placebo + IG-treated patients reached HbA1c <7.0% (<53 mmol/mol) (32.5% vs 7.4%; P < .001); daily IG dose increased by 2 and 4 units, respectively. Gastrointestinal and injection-site adverse events were more frequent with exenatide QW + IG (15.1% and 7.8%, respectively) than with placebo + IG (10.8% and 3.0%, respectively); hypoglycaemia incidence was similar between the exenatide QW + IG (29.7%) and placebo + IG (29.0%) groups, with no major hypoglycaemic events.. Among patients with inadequate glycaemic control, exenatide QW significantly improved glucose control and decreased body weight, without increased hypoglycaemia or unexpected safety findings.

Topics: Aged; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Exenatide; Female; Follow-Up Studies; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin Glargine; Male; Middle Aged; Obesity; Weight Loss

To test the safety and efficacy of MYL-1501D, a proposed insulin glargine biosimilar, in patients with type 1 diabetes mellitus (T1DM).. The safety and efficacy of MYL-1501D and reference insulin glargine were evaluated in INSTRIDE 1, a 52-week, open-label, randomized, phase III study in patients with T1DM. The primary objective was to determine whether once-daily MYL-1501D was non-inferior to once-daily insulin glargine when administered in combination with mealtime insulin lispro based on change in glycated haemoglobin (HbA1c) from baseline to week 24. Secondary endpoints were changes in fasting plasma glucose, insulin dose, self-monitored blood glucose and immunogenicity from baseline, and occurrences of hypoglycaemic, nocturnal hypoglycaemic and adverse events up to week 52.. Overall, 558 patients were randomized 1:1 to MYL-1501D or reference insulin glargine in combination with thrice-daily mealtime insulin lispro for 52 weeks. The mean change in HbA1c from baseline to week 24 was 0.14% (standard error [SE] 0.054; 95% confidence interval [CI] 0.033, 0.244) for MYL-1501D and 0.11% (SE 0.054; 95% CI 0.007, 0.220) for reference insulin glargine. MYL-1501D had a safety profile similar to that of reference insulin glargine and was well tolerated in patients with T1DM up to week 52.. The upper 95% CI limit for mean change in HbA1c at week 24 indicated that MYL-1501D was non-inferior to reference insulin glargine. There were no clinically meaningful differences between groups in incidence of overall and nocturnal hypoglycaemia, local or systemic reactions, safety or immunogenicity.

Topics: Activities of Daily Living; Biosimilar Pharmaceuticals; Blood Glucose; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin Lispro; Meals; Overweight; Severity of Illness Index

To compare the efficacy and safety of MK-1293 insulin glargine (Mk-Gla) and Lantus (Sa-Gla) in people with type 2 diabetes mellitus (T2DM).. This Phase 3, randomized, active-controlled, open-label, 24-week clinical trial (ClinicalTrials.gov number NCT02059187) enrolled 531 participants with T2DM (HbA1c ≤11.0%) either eligible for or currently taking basal insulin (≥10 U/day). Participants were randomized 1:1 to once-daily Mk-Gla (n = 263) or Sa-Gla (n = 263). Titration of insulin was guided by a fasting plasma glucose (FPG)-based dosing algorithm. The primary efficacy objective was to demonstrate the non-inferiority of change from baseline in HbA1c (margin of 0.40% [4.4 mmol/mol]) with Mk-Gla versus Sa-Gla after 24 weeks. The primary safety objective was anti-insulin antibody development after 24 weeks.. For Mk-Gla and Sa-Gla, the least squares (LS) mean HbA1c change from baseline (95% CI) was -1.28 (-1.41, -1.15)% (-14.0 [-15.4, -12.6] mmol/mol) and -1.30 (-1.43, -1.18)% (-14.2 [-15.6, -12.8] mmol/mol). The LS mean HbA1c difference (Mk-Gla minus Sa-Gla) was 0.03 (-0.12, 0.18)% (0.3 [-1.4, 1.9] mmol/mol), meeting non-inferiority and equivalence (secondary objective) criteria. Insulin doses, FPG, and seven-point plasma glucose profiles were similar between groups. Safety and tolerability, including anti-insulin antibody responses, hypoglycaemia, adverse events and body weight, were similar between insulins. The efficacy and safety of Mk-Gla and Sa-Gla were similar both in participants who were insulin-treated or insulin-naïve at baseline.. Mk-Gla and Sa-Gla demonstrated similar efficacy and safety over 24 weeks of treatment in people with T2DM.

Topics: Aged; Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Antibodies; Insulin Glargine; Least-Squares Analysis; Male; Middle Aged; Treatment Outcome

To compare the efficacy and safety of MK-1293 insulin glargine (Mk-Gla; 100 U/mL) with originator insulin glargine, Lantus (Sa-Gla), in people with type 1 diabetes mellitus (T1DM).. This phase 3, randomized, active-controlled, open-label, 52-week study (ClinicalTrials.gov NCT02059161) enrolled 508 people with T1DM (HbA1c ≤11.0%; 97 mmol/mol) taking basal and prandial insulin. Participants were randomized 1:1 to once-daily Mk-Gla (n = 245) or Sa-Gla (n = 263). Dose titration of basal insulin was by a pre-breakfast plasma glucose dosing algorithm. The primary efficacy objective was assessment of the non-inferiority of HbA1c change from baseline (margin of 0.40% [4.4 mmol/mol]) for Mk-Gla compared with Sa-Gla over 24 weeks. The primary safety objective was assessment of anti-insulin antibody development over 24 weeks.. The least squares (LS) mean HbA1c change from baseline at week 24 was -0.62 (95% CI -0.79, -0.45)% (-6.8 [-8.7, -4.9] mmol/mol) and -0.66 (-0.82, -0.50)% (-7.2 [-9.0, -5.4] mmol/mol) for Mk-Gla and Sa-Gla. The LS mean HbA1c difference was 0.04 (-0.11, 0.19)% (0.4 [-1.2, 2.0] mmol/mol) for Mk-Gla minus Sa-Gla, meeting the primary and secondary objective criteria for non-inferiority and equivalence. Week 24 mean insulin glargine dose for Mk-Gla and Sa-Gla was 0.46 and 0.48 U/kg, respectively. Similarity of HbA1c response and basal insulin dose trajectory persisted over the 52 weeks. Safety and tolerability, including anti-insulin antibody responses, hypoglycaemia, adverse events and body weight, were similar between insulins over the 52-week study duration.. Mk-Gla and Sa-Gla exhibited similar efficacy and safety over 52 weeks in people with T1DM. ClinicalTrials.gov: NCT02059161.

Topics: Adult; Algorithms; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Antibodies; Insulin Glargine; Least-Squares Analysis; Male; Middle Aged; Treatment Outcome

Treatment with basal insulin in Chinese populations is currently sub-optimal, with delayed initiation of insulin treatment and inadequate dose titration. Increasing the initial dose of insulin may be a practicable and effective solution to the problem of titration. A higher initial dose will be helpful for patients to achieve the blood glucose target and improve treatment satisfaction and compliance as well require fewer steps to titrate. Considering that overweight and obese patients usually require higher insulin doses because of insulin resistance, a higher initial dose of the basal insulin is feasible in overweight and obese patients with type 2 diabetes. However, safety is an important issue needing to be considered for higher initial dose treatment. The aim of this study is to assess the safety and efficacy of higher (0.3 U/kg) compared with standard (0.2 U/kg) starting doses of basal insulin in overweight and obese Chinese patients with type 2 diabetes who have failed to achieve glycaemic control using oral antidiabetic drugs (OADs).. This is a phase IV, randomized, non-inferiority, open-label trial that will be conducted at approximately 50 centers in China. Eight hundred eighty overweight and obese adult Chinese patients with type 2 diabetes will be randomized to receive higher (0.3 U/kg) or standard (0.2 U/kg) starting doses of basal insulin glargine (100 U/ml) during a 16-week period. The primary endpoint is whether a higher initial dose of basal insulin (0.3 U/kg) is non-inferior to a standard initial dose (0.2 U/kg) based on the percentage of patients with at least one episode of hypoglycaemia (≤ 3.9 mmol/l or severe) over 16 weeks. Secondary endpoints include evaluation of glycosylated haemoglobin A1c (HbA1c), fasting blood glucose, postprandial blood glucose, insulin dose and safety.. This study is the first randomized-controlled study to evaluate the safety and efficacy of basal insulin treatment with a higher starting dose versus standard starting dose in overweight and obese Chinese patients with type 2 diabetes. Results of this study could generate evidence to support the feasibility of a higher starting dose of basal insulin in diabetes management of overweight and obese Chinese patients, therefore providing an easy approach to improve diabetes management.. ClinicalTrials.gov identifier, NCT02836704. Registered on July 7th 2016.. Sanofi China.

Topics: Adult; Aged; Aged, 80 and over; China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Overweight

To explore if clinical effects and hypoglycaemia risks associated with insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100) differed by sulphonylurea and/or glinide (SU/G) treatment.. A post hoc subgroup analysis of 12-month treatment data from the EDITION Japan 2 trial, a randomized, open-label, phase 3 study of Japanese people with type 2 diabetes receiving once-daily Gla-300/Gla-100 + oral antihyperglycaemic drugs. Participants previously receiving SU/G (+SU/G) were compared with those not taking SU/G (-SU/G). Endpoints included HbA1c, hypoglycaemia and body weight.. For +SU/G (n = 152, 63%), HbA1c was reduced from baseline to month 12 for Gla-300 (8.1% to 7.6%) and Gla-100 (8.2% to 7.8%). For -SU/G (n = 89, 37%), reductions were 7.8% to 7.4%, and 7.9% to 7.5% for Gla-300 and Gla-100, respectively. A lower annualized rate of hypoglycaemia with Gla-300 versus Gla-100 was observed at night (00:00-05:59 hours; p = 0.0001) and any time of day (24 hour; p = 0.0015). Irrespective of the insulin used, the incidence and rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia appeared higher in +SU/G versus -SU/G; overall, a reduced incidence of nocturnal hypoglycaemia, and rate of hypoglycaemia at any time, was observed in -SU/G versus +SU/G. In the -SU/G subgroup, body weight gain differences were observed between Gla-300 and Gla-100 (p < 0.0001).. Participants with prior and continued SU/G use had similar therapeutic responses with basal insulin but greater risk of hypoglycaemia than those not using SU/G; hypoglycaemia risk was lower with Gla-300 than Gla-100 in both subgroups.

Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Middle Aged; Sulfonylurea Compounds

Few studies have evaluated continuous glucose monitoring (CGM) in older patients with type 2 diabetes mellitus (T2DM) not using injectable therapy. CGM is useful for investigating hypoglycemia and glycemic variability, which is associated with complications in T2DM.. A CGM substudy of Individualized treatMent aPproach for oldER patIents in a randomized trial in type 2 diabetes Mellitus (IMPERIUM)) was conducted. Patients were vulnerable (moderately ill and/or frail) older (≥65 years) individuals with suboptimally controlled T2DM. Strategy A comprised glucose-dependent therapies (n = 26) with a nonsulfonylurea oral antihyperglycemic medication (OAM) and a glucagon-like peptide-1 receptor agonist as the first injectable. Strategy B comprised non-glucose-dependent therapies (n = 21) with sulfonylurea as the preferred OAM and insulin glargine as the first injectable. Primary endpoints were duration and percentage of time spent with blood glucose (BG) ≤70 mg/dL over 24 hours at week 24.. Duration and percentage of time spent with hypoglycemia at ≤70 mg/dL were similar for Strategy A and Strategy B; glycemic control improved similarly in both arms (LSM change in HbA1c at week 24; A = -1.2%, B = -1.4%). Duration and percentage time spent with euglycemia and hyperglycemia were also similar in both arms. However, Strategy A was associated with lower within-day (21.1 ± 1.2 vs 25.1 ± 1.4, P = .046) and between-day (5.4 ± 1.0 vs 9.1 ± 1.3, P = .038) BG variability (coefficient of variance [LSM ± SE]) at week 24.. This CGM substudy in older patients with T2DM showed lower within- and between-day BG variability with glucose-dependent therapies but similar HbA1c reductions and hypoglycemia duration with glucose-independent strategies.

Topics: Age Factors; Aged; Aged, 80 and over; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Female; Frail Elderly; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Injections, Subcutaneous; Insulin Glargine; Male; Sulfonylurea Compounds; Treatment Outcome

SENIOR compared the efficacy and safety of insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in older people (≥65 years old) with type 2 diabetes.. SENIOR was an open-label, two-arm, parallel-group, multicenter phase 3b trial designed to enroll ∼20% of participants aged ≥75 years. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to a fasting self-monitored plasma glucose of 5.0-7.2 mmol/L (90-130 mg/dL).. Efficacy and safety of Gla-300 was demonstrated in older people (≥65 years of age) with type 2 diabetes, with comparable reductions in HbA

Topics: Aged; Aged, 80 and over; Aging; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Male; Treatment Outcome

To evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.. This multicentre, open-label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once-daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC. Lixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

Topics: Administration, Oral; Aged; Biomarkers; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Emptying; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Japan; Male; Middle Aged; Peptides; Postprandial Period; Sitagliptin Phosphate

To assess the impact of baseline characteristics on clinical outcomes in the LixiLan-L trial, a randomized open-label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed-ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with 1 or 2 oral glucose-lowering drugs.. Compared with the iGlar treatment group, patients treated with iGlarLixi showed consistently greater reductions in HbA1c during the treatment period, with higher percentages of patients achieving the HbA1c target level of <7% (<53 mmol/mol) in all of the subpopulations tested (P < .0001 for all), having consistent mitigation of body weight gain and with no major differences in the incidence of hypoglycaemia.. iGlarLixi consistently improved glycaemic control compared with iGlar in all baseline characteristic subgroups of patients with T2DM inadequately controlled with insulin, including difficult-to-treat subgroups of patients with long duration of diabetes, obesity and high HbA1c. Clinical trial number: NCT02058160 (clinicaltrials.gov).

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Glargine; Male; Middle Aged; Peptides; Time Factors

Primary objective: Identify risk factors associated with severe hypoglycemia (SH) and investigate the association between mild hypoglycemia and SH in people with type 2 diabetes starting insulin. Secondary objectives: Investigate the association of demographics and clinical factors with SH incidence.. Integrated trial database data were obtained for 3 randomized controlled trials that included insulin-naïve people with type 2 diabetes initiating basal (insulin glargine) versus biphasic (insulin lispro mixture) insulin. Standard definitions were used for SH; mild hypoglycemia was defined as all non-SH. Cox regression identified risk factors associated with SH and the correlation between SH and mild hypoglycemia.. Data were pooled (N=2931). During 24-48weeks' treatment, 2127 (72.6%) participants experienced ≥1 mild hypoglycemic event but no SH (mean mild hypoglycemia rate=2.33/month). 56 participants (1.9%) experienced ≥1 SH event plus mild hypoglycemia (mean mild hypoglycemia rate=3.95/month); 748 participants (25.5%) had no hypoglycemia. Among factors tested, only mild hypoglycemia rate/month was associated with SH. SH risk was higher (HR=4.24; 95%CI=2.57-6.99;p<0.0001) for participants experiencing multiple mild hypoglycemic events/month compared with those experiencing ≤1 mild hypoglycemic event/month.. Mild hypoglycemia may predict the first SH event, which is important because SH is a strong and consistent risk factor for morbidity/mortality.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin Lispro; Male; Middle Aged; Risk Factors; Severity of Illness Index

Topics: Body Mass Index; Diabetes Mellitus, Type 2; Disease Progression; Drug Combinations; Drug Resistance; Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Insulin Glargine; Middle Aged; Obesity; Peptides; Postprandial Period; Weight Gain

To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months.. EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed.. Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Middle Aged; Treatment Outcome

To determine whether previously reported reductions in hypoglycemia associated with insulin glargine 300 U/mL (Gla-300) compared with insulin glargine 100 U/mL (Gla-100) are impacted by patient risk category in type 2 diabetes (T2D), clinical performance measures based on the Healthcare Effectiveness Data and Information Set (HEDIS) were applied to patient-level data from the EDITION 2 and EDITION 3 clinical trials that compared Gla-300 and Gla-100.. In this post hoc analysis, patients were stratified as low risk (LR) if patients were <65 years old with no comorbidities derived from HEDIS (HbA1c target <7.0% [53 mmol/mol]), or as high risk (HR) if patients were either ≥65 years old or had one or more HEDIS-defined comorbidities (HbA1c target <8.0% [64 mmol/mol]). Primary endpoint was a composite of patients achieving HbA1c target without confirmed or severe hypoglycemia over 6 months in the different treatment groups in each of the EDITION trials.. There was a statistically nonsignificant trend of more patients treated with Gla-300 achieving the composite endpoint compared with Gla-100 in both the LR and HR patient cohorts, regardless of prior insulin experience. A similar trend was observed for the composite endpoint of HbA1c target without nocturnal hypoglycemia.. There is a consistent, nonsignificant trend suggesting that Gla-300 might reduce the burden of hypoglycemia compared with Gla-100 in patients with T2D irrespective of whether they are classed as LR or HR based on age- and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set-derived comorbidities.

Topics: Activities of Daily Living; Aged; Cohort Studies; Delayed-Action Preparations; Diabetes Complications; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Middle Aged; Osmolar Concentration; Reproducibility of Results; Retrospective Studies; Risk; Severity of Illness Index; United States

We have previously reported that once-weekly albiglutide was noninferior to thrice-daily lispro for glycemic lowering, with decreased weight and risk of hypoglycemia, in patients inadequately controlled on basal insulin over 26 weeks. Findings after 52 weeks reveal similar responses to albiglutide as an add-on to insulin glargine.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Incretins; Insulin Glargine; Insulin Lispro; Meals; Risk; Weight Gain; Weight Loss

Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec.. We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome.. Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups.. Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529 .).

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Kaplan-Meier Estimate; Male; Middle Aged

To explore if efficacy and safety findings for insulin glargine 300U/mL (Gla-300) versus insulin glargine 100U/mL (Gla-100), observed over 6 months in insulin-naïve people with type 2 diabetes, are maintained after 12 months.. EDITION 3 was a phase 3a, randomized, multicentre, open-label, parallel-group, treat-to-target study of once-daily Gla-300 versus Gla-100 (target fasting self-monitored plasma glucose, 4.4-5.6mmol/L [80-100mg/dL]). Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin.

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Treatment Outcome; Young Adult

Subcutaneous insulin glargine/lixisenatide (Suliqua™) is a titratable, fixed-ratio combination of a long-acting basal insulin analogue and a glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of adult patients with inadequately controlled type 2 diabetes. Once-daily insulin glargine/lixisenatide, in combination with metformin, provided effective glycaemic control and was generally well tolerated in the 30-week, multinational, phase 3 LixiLan-O and LixiLan-L trials in insulin-naive and -experienced adult patients with inadequately controlled type 2 diabetes. Although long-term clinical experience with this fixed-ratio combination is currently lacking, given its convenient once-daily regimen and beneficial effects on glycaemic control and bodyweight loss in the absence of an increase in the incidence of hypoglycaemia, insulin glargine/lixisenatide is an emerging option for the treatment of adult patients with type 2 diabetes to improve glycaemic control when this has not been provided by metformin alone or metformin combined with another OAD or basal insulin.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Metformin; Peptides

Hypoglycemia, common in patients with type 1 diabetes, is a major barrier to achieving good glycemic control. Severe hypoglycemia can lead to coma or death.. To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes.. Double-blind, randomized, crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers (January 2014-January 12, 2016) for two 32-week treatment periods, each with a 16-week titration and a 16-week maintenance period.. Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 249) or to receive insulin glargine U100 followed by insulin degludec (n = 252) and randomized 1:1 to morning or evening dosing within each treatment sequence.. The primary end point was the rate of overall severe or blood glucose-confirmed (<56 mg/dL) symptomatic hypoglycemic episodes during the maintenance period. Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period. The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95% CI for a rate ratio of 1.10 or lower; if noninferiority was established, 2-sided statistical testing for superiority was conducted.. Of the 501 patients randomized (mean age, 45.9 years; 53.7% men), 395 (78.8%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years' exposure (PYE) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio (RR) of 0.89 (95% CI, 0.85-0.94; P < .001 for noninferiority; P < .001 for superiority; rate difference, -130.31 episodes per 100 PYE; 95% CI, -193.5 to -67.16). The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group, for an RR of 0.64 (95% CI, 0.56-0.73; P < .001 for noninferiority; P < .001 for superiority; rate difference, -61.94 episodes per 100 PYE; 95% CI, -83.85 to -40.03). A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period (10.3%, 95% CI, 7.3%-13.3% vs 17.1%, 95% CI, 13.4%-20.8%, respectively; McNemar P = .002; risk difference, -6.8%; 95% CI, -10.8% to -2.7%).. Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia, 32 weeks' treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemic episodes.. clinicaltrials.gov Identifier: NCT02034513.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Risk Factors

Hypoglycemia, a serious risk for insulin-treated patients with type 2 diabetes, negatively affects glycemic control.. To test whether treatment with basal insulin degludec is associated with a lower rate of hypoglycemia compared with insulin glargine U100 in patients with type 2 diabetes.. Randomized, double-blind, treat-to-target crossover trial including two 32-week treatment periods, each with a 16-week titration period and a 16-week maintenance period. The trial was conducted at 152 US centers between January 2014 and December 2015 in 721 adults with type 2 diabetes and at least 1 hypoglycemia risk factor who were previously treated with basal insulin with or without oral antidiabetic drugs.. Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 361) or to receive insulin glargine U100 followed by insulin degludec (n = 360) and randomized 1:1 to morning or evening dosing within each treatment sequence.. The primary end point was the rate of overall symptomatic hypoglycemic episodes (severe or blood glucose confirmed [<56 mg/dL]) during the maintenance period. Secondary end points were the rate of nocturnal symptomatic hypoglycemic episodes (severe or blood glucose confirmed, occurring between 12:01 am and 5:59 am) and the proportion of patients with severe hypoglycemia during the maintenance period.. Of the 721 patients randomized (mean [SD] age, 61.4 [10.5] years; 53.1% male), 580 (80.4%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were 185.6 vs 265.4 episodes per 100 patient-years of exposure (PYE) (rate ratio = 0.70 [95% CI, 0.61-0.80]; P < .001; difference, -23.66 episodes/100 PYE [95% CI, -33.98 to -13.33]), and the proportions of patients with hypoglycemic episodes were 22.5% vs 31.6% (difference, -9.1% [95% CI, -13.1% to -5.0%]). The rates of nocturnal symptomatic hypoglycemia with insulin degludec vs insulin glargine U100 were 55.2 vs 93.6 episodes/100 PYE (rate ratio = 0.58 [95% CI, 0.46-0.74]; P < .001; difference, -7.41 episodes/100 PYE [95% CI, -11.98 to -2.85]), and the proportions of patients with hypoglycemic episodes were 9.7% vs 14.7% (difference, -5.1% [95% CI, -8.1% to -2.0%]). The proportions of patients experiencing severe hypoglycemia during the maintenance period were 1.6% (95% CI, 0.6%-2.7%) for insulin degludec vs 2.4% (95% CI, 1.1%-3.7%) for insulin glargine U100 (McNemar P = .35; risk difference, -0.8% [95% CI, -2.2% to 0.5%]). Statistically significant reductions in overall and nocturnal symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were also seen for the full treatment period.. Among patients with type 2 diabetes treated with insulin and with at least 1 hypoglycemia risk factor, 32 weeks' treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemia.. clinicaltrials.gov Identifier: NCT02030600.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Risk Factors

SAR342434 is a biosimilar follow-on of insulin lispro-Humalog. SORELLA-1 was a randomized, open-label phase 3 study (NCT02273180). Patients completing the 6-month main study continued on SAR-Lis or Ly-Lis, as randomized, for a 6-month safety extension. Assessments included change in HbA. Five hundred seven patients were randomized (SAR-Lis n = 253; Ly-Lis n = 254). Least square (LS) mean (SEM) change in glycosylated hemoglobin (HbA1c) (baseline to week 26; primary endpoint) was similar in both treatment groups (SAR-Lis: -0.42% [0.051]; Ly-Lis: -0.47% [0.050]). Noninferiority at prespecified 0.3% noninferiority margin and inverse noninferiority were demonstrated (LS mean difference of SAR-Lis vs. Ly-Lis: 0.06% [95% confidence interval: -0.084 to 0.197]). At week 52 (end of extension period) versus week 26, a small HbA1c increase was observed in both groups. FPG and seven-point SMPG profile changes, including postprandial glucose excursions, were similar between groups. At week 52, similar changes in mean daily mealtime and basal insulin doses were observed. Hypoglycemia, TEAEs, and AIAs (incidence, prevalence) did not differ between groups.. Results from this controlled study in patients with T1DM also using GLA-100 support similar efficacy and long-term safety (including immunogenicity) of SAR-Lis and Ly-Lis.

Topics: Adult; Autoantibodies; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Hypersensitivity; Drug Therapy, Combination; Equivalence Trials as Topic; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Injections, Subcutaneous; Insulin Glargine; Insulin Lispro; Intention to Treat Analysis; Patient Dropouts; Prevalence

Basal insulin peglispro (BIL) has a peripheral-to-hepatic distribution of action that resembles endogenous insulin and a prolonged duration of action with a flat pharmacokinetic/pharmacodynamic profile at steady state, characteristics that tend to reduce hypoglycemia risk compared to insulin glargine (GL). The primary objective was to demonstrate that clinically significant hypoglycemia (blood glucose ≤54 mg/dL [3.0 mmol/L] or symptoms of severe hypoglycemia) occurred less frequently within 84 h after a double dose (DD) of BIL than a DD of GL.. This was a randomized, double-blind, two-period crossover study in patients with type 2 diabetes (T2D) previously treated with insulin (N = 68). For the first 3 weeks of each of the two crossover periods, patients received an individualized dose of BIL or GL once nightly (stable dose for 2 weeks/period). Then, during a 7-day inpatient stay with frequent blood glucose monitoring and standardized meals, one DD of study insulin was given. Glucose was infused if blood glucose was ≤54 mg/dL (3.0 mmol/L) or for symptoms of severe hypoglycemia.. Within 84 h after the DD, a significantly smaller proportion of patients experienced clinically significant hypoglycemia with BIL compared to GL (BIL, 6.6%; GL, 35.5%; odds ratio for BIL/GL 0.13 [95% confidence interval 0.04-0.39]; P < 0.001). Adverse event profiles were similar for the two insulins. Serum alanine aminotransferase and triglyceride levels were significantly higher with BIL versus GL.. BIL has a markedly lower risk of hypoglycemia than GL when replicating a double-dose error in patients with T2D.

Topics: Adolescent; Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Male; Middle Aged; Polyethylene Glycols; Risk; Treatment Outcome; Young Adult

To investigate whether sodium glucose co-transporter 2 inhibitors (SGLT2i), tofogliflozin or ipragliflozin, achieve optimal glycemic variability, when used together with insulin glargine 300 U/mL (Glargine 300). Thirty patients with type 2 diabetes were randomly allocated to 2 groups. For the first group: After admission, tofogliflozin 20 mg was administered; Fasting plasma glucose (FPG) levels were titrated using an algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using continuous glucose monitoring (CGM); Tofogliflozin was then washed out over 5 days; Subsequently, ipragliflozin 50 mg was administered; FPG levels were titrated using the same algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using CGM. For the second group, ipragliflozin was administered prior to tofogliflozin, and the same regimen was maintained. Glargine 300 and SGLT2i were administered at 8:00 AM. Data collected on the second day of measurement (mean amplitude of glycemic excursion [MAGE], average daily risk range [ADRR]; on all days of measurement) were analyzed. Area over the glucose curve (<70 mg/dL; 0:00 to 6:00, 24-h), M value, standard deviation, MAGE, ADRR, and mean glucose levels (24-h, 8:00 to 24:00) were significantly lower in patients on tofogliflozin than in those on ipragliflozin. Tofogliflozin, which reduces glycemic variability by preventing nocturnal hypoglycemia and decreasing postprandial glucose levels, is an ideal SGLT2i when used together with Glargine 300 during basal insulin therapy.

Topics: Activities of Daily Living; Aged; Benzhydryl Compounds; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucosides; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Membrane Transport Modulators; Middle Aged; Monitoring, Ambulatory; Risk; ROC Curve; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes

To investigate, in a 26-week, open-label, randomized, treat-to-target trial, the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily vs insulin glargine (IGlar) once daily in adults with Type 2 diabetes, inadequately controlled on basal insulin.. Participants were randomized (1:1) to IDegAsp once daily or IGlar once daily in combination with existing oral antidiabetic drugs. IDegAsp once daily was administered with the main evening meal or the largest meal of the day (agreed at baseline); dosing time was maintained throughout the trial. Participants titrated their insulin dose weekly to a mean pre-breakfast self-measured plasma glucose target [3.9-4.9 mmol/l (70-89 mg/dl)].. In participants with Type 2 diabetes inadequately controlled on basal insulin, IDegAsp once daily improved glycaemic control and was non-inferior to IGlar once daily. IDegAsp led to higher rates of overall hypoglycaemia than IGlar, with no significant difference in rates of nocturnal hypoglycaemia.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Care Planning; Treatment Outcome

Hyperglycemia is a major complication of parenteral nutrition (PN). Guidelines for hyperglycemia management in noncritically ill patients cite basal insulin administration but do not recommend a regimen. The GLUCOSE-in-PN study aimed to compare the efficacy of glargine insulin versus continuously infused regular insulin in PN (RI-in-PN) to achieve glycemic control in noncritically ill surgical patients with diabetes who were receiving PN.. This prospective randomized open-label study was conducted at King Faisal Specialist Hospital and Research Centre. Noncritically ill surgical patients with diabetes who were receiving PN were randomized to receive basal glargine insulin or RI-in-PN on day 4 of PN support. Mean blood glucose levels were compared on study days 5-9. The percentages of blood glucose measurements at goal were compared between groups.. Sixty-seven PN treatment episodes were analyzed. There were no statistically significant differences in mean glucose levels between groups on any study day ( P > .1). Overall glycemic control rates were 52.24% (glargine insulin) and 47.76% (RI-in-PN; P = .06). A significantly higher percentage of hyperglycemia was observed on day 5 for glargine insulin versus RI-in-PN (22.39% vs 5.97%, P = .0059). Blood glucose measurements indicated 6 hypoglycemic events: 2 for glargine insulin (5.7%) and 4 for RI-in-PN (11.4%; P > .1).. Both glargine insulin and RI-in-PN are effective basal insulin modalities for blood glucose control in noncritically ill surgical patients with diabetes who are receiving PN. Uncontrolled hyperglycemic events occurred more frequently with glargine insulin, and the rate of hypoglycemia was acceptable for both regimens.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Male; Middle Aged; Parenteral Nutrition; Postoperative Care; Prospective Studies

This study implemented a randomized crossover design to evaluate the efficacy and safety of switching from insulin glargine (IGlar) to insulin degludec (IDeg) in 18 children (11 males, 7 females; age 11.0 ± 0.5 years) with type 1 diabetes. All subjects had previously used IGlar once daily at bedtime. We compared fasting plasma glucose (FPG) and HbA1c levels, frequencies of overall and nocturnal (2200 h - 0659 h) hypoglycemia, and basal insulin dose at the baseline with those measured during a 24-week period during which IGlar or IDeg was administered in combination with pre-meal rapid acting insulin analogues. IDeg was initially given at the same dose as IGlar but was subsequently titrated to achieve FPG levels of 90-140 mg/dL. There were no significant changes in FPG and HbA1c levels from the baseline during the 24-week study period with IGlar or IDeg. The daily basal insulin dose did not significantly differ with IGlar or IDeg. Although the frequencies of overall hypoglycemia were similar, nocturnal hypoglycemia significantly decreased at 12 and 24 weeks from the baseline with IDeg use (2 ± 0.4 vs. 0 ± 0.3, 0 ± 0.5 episodes/month, both P <0.05), whereas no significant change in the frequency of nocturnal hypoglycemia was observed with IGlar. No severe hypoglycemia occurred during the study period with either basal insulin analogues. These results suggest that IDeg, injected once at bedtime, may provide similar glycemic control as IGlar while better reducing the risk of nocturnal hypoglycemia in children with type 1 diabetes.

Topics: Adolescent; Blood Glucose; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Substitution; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients.. Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system.. On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P  = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P  = .57) or glucose <4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P  = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P  = .02) and the insulin dose was increased over time ( P  = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P  = .45) or between groups ( P  = .24).. There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia.

Topics: Aged; Blood Glucose; Drug Administration Schedule; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Male; Meals; Middle Aged; Prednisolone; Treatment Outcome

The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin.. In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events.. Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged

Effective glycemic control can reduce the risk of complications and their related costs in type 2 diabetes mellitus (T2DM). However, many patients fail to reach glycemic targets, often because of adverse effects of treatment (including hypoglycemia or weight gain). The present analysis evaluated the short-term cost-effectiveness of IDegLira versus continued up-titration of insulin glargine U100 in patients with T2DM failing to achieve glycemic control on basal insulin in the US setting.. The cost per patient achieving treatment target (cost of control) was assessed for various single and composite endpoints for the entire trial population and in patients with baseline glycated hemoglobin (HbA1c) >8.0% and HbA1c >9.0%. The proportions of patients achieving treatment targets were analyzed using data obtained in the DUAL V study. Costs were accounted based on published wholesale acquisition costs.. When assessing the full trial population, IDegLira was associated with lower annual cost of control than continued up-titration of insulin glargine U100 for patients achieving HbA1c ≤6.5% without confirmed hypoglycemia (by $10,608), HbA1c ≤6.5% without weight gain (by $29,215), and HbA1c ≤6.5% without confirmed hypoglycemia and weight gain (by $57,351). A similar pattern was observed when multifactorial treatment targets were based on achieving a glycemic target of 7.0%. When only HbA1c was considered, IDegLira was associated with a lower cost per patient achieving HbA1c ≤6.5% (by $3306) but cost of control was equivalent for a target of HbA1c <7.0%. In patients with baseline HbA1c >8.0% and HbA1c >9.0%, IDegLira was associated with a lower cost of control for all treatment targets.. The significantly greater clinical efficacy in terms of bringing patients to treatment targets identified in the DUAL V study results in lower cost of control values for IDegLira versus continued up-titration of insulin glargine U100 in the USA. This suggests IDegLira is a cost-effective treatment option in the USA.. Novo Nordisk A/S and Novo Nordisk Inc.

Topics: Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Weight Gain

To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimum glycated haemoglobin (HbA1c) concentration.. Patients (N = 300) from this phase III, double-blind, parallel-arm, placebo-controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks.. Least squares (LS) mean ± standard error (s.e.) HbA1c changes from baseline were -1.44 ± 0.09% (-15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and -0.67 ± 0.09% (-7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks (LS mean difference [95% confidence interval] -0.77% [-0.97, -0.56]; P < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: -2.41 ± 0.39 kg; P < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (P = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%).. Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D.

Topics: Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Incretins; Injections, Subcutaneous; Insulin Glargine; Intention to Treat Analysis; Male; Middle Aged; Patient Dropouts; Recombinant Fusion Proteins

To compare day-to-day and within-day variability in glucose-lowering effect between insulin degludec (IDeg) and insulin glargine 300 U/mL (IGlar-U300) in type 1 diabetes.. In this double-blind, crossover study, patients were randomly assigned to 0.4 U/kg of IDeg or IGlar-U300 once daily for two treatment periods lasting 12 days each. Pharmacodynamic variables were assessed at steady-state from the glucose infusion rate profiles of three 24-hour euglycaemic glucose clamps (days 6, 9 and 12) during each treatment period.. Overall, 57 patients completed both treatment periods (342 clamps). The potency of IGlar-U300 was 30% lower than IDeg (estimated ratio 0.70, 95% confidence interval [CI] 0.61; 0.80; P  < .0001). The distribution of glucose-lowering effect was stable across 6-hour intervals (24%-26%) for IDeg, while IGlar-U300 had greater effects in the first (35%) and last (28%) intervals compared with 6 to 12 hours (20%) and 12 to 18 hours (17%). Within-day variability (relative fluctuation) was 37% lower with IDeg than with IGlar-U300 (estimated ratio IDeg/IGlar-U300: 0.63, 95% CI 0.54; 0.73; P  < .0001). The day-to-day variability in glucose-lowering effect with IDeg was approximately 4 times lower than IGlar-U300 (variance ratio IGlar-U300/IDeg: 3.70, 95% CI 2.42; 5.67; P  < .0001). The day-to-day variability in glucose-lowering effect assessed in 2-hour intervals was consistently low with IDeg over 24 hours, but steadily increased with IGlar-U300 to a maximum at 10 to 12 hours and 12 to 14 hours after dosing (variance ratios 12.4 and 11.4, respectively).. IDeg has lower day-to-day and within-day variability than IGlar-U300 and a more stable glucose-lowering effect, which might facilitate titration and enable tighter glycaemic control with a reduced risk of hypoglycaemia.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Male; Middle Aged; Reproducibility of Results

The aim of the present 24-week multicentre randomized non-inferiority trial was to compare the efficacy and safety of two insulin intensification strategies in uncontrolled type 2 diabetes despite optimized basal insulin therapy.. Patients with fasting plasma glucose (FPG) <130 mg/dL and HbA1c 7.0%-10.0% while on insulin glargine were randomized to a basal-prandial group (stepwise addition of insulin glulisine) or a premixed insulin group (insulin aspart/insulin aspart protamine 30/70 starting with 6 IU twice daily). The primary endpoint was the change in HbA1c after 24 weeks (non-inferiority margin 0.4%).. At Week 24, the adjusted mean change from baseline HbA1c was -0.94 ± 0.09% and -1.04 ± 0.09% in basal-prandial and premixed insulin groups, respectively, with a mean difference of -0.09% (95% confidence interval [CI] -0.35, 0.16). A lower rate of hypoglycemia with a similar reduction in HbA1c was observed during stabilization of the total daily insulin dose in the premixed insulin group (Weeks 0-12). After stabilization of the total daily insulin dose, the rate of hypoglycemia and the total daily insulin dose were similar in the two groups.. The efficacy and safety of the two intensifying regimens were similar after stabilization of the total daily insulin dose when oral agents were maintained. Starting with a lower total daily insulin dose with a gradual change in the treatment regimen was helpful in reducing the rate of hypoglycemia during initial stabilization of the total daily insulin dose.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Male; Time Factors

To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes.. Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM). In a randomized and counterbalanced order, the participants were administered an individualized dose of rapid-acting insulin (2 ± 1 units, range 0-4 units) immediately after resistance exercise (insulin session) by means of an algorithm or were not administered this (no-insulin session). Venous blood glucose concentrations were measured for 125 min after resistance exercise. Data (mean ± sem values) were analysed using anova (P ≤ 0.05).. Participants had immediate post-resistance exercise hyperglycaemia (insulin session 13.0 ± 1.6 vs. no-insulin session 12.7 ± 1.5 mmol/l; P = 0.834). The decline in blood glucose concentration between peak and 125 min after exercise was greater in the insulin exercise session than in the no-insulin session (3.3 ± 1.0 vs. 1.3 ± 0.4 mmol/l: P = 0.015). There were no episodes of hypoglycaemia (blood glucose <3.9 mmol/l).. Administration of rapid-acting insulin according to an individualized algorithm reduced the hyperglycaemia associated with morning resistance exercise without causing hypoglycaemia in the 2 h post-exercise period in people with Type 1 diabetes.

Topics: Adult; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin Glargine; Pilot Projects; Precision Medicine; Resistance Training; Risk; United Kingdom

Topics: Cross-Over Studies; Diabetes Mellitus, Type 1; Glycemic Index; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Prognosis; Time Factors

To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM).. To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test.. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes.. LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Topics: Asymptomatic Diseases; Biosimilar Pharmaceuticals; Cross Reactions; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Hypersensitivity; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Immunogenetic Phenomena; Incidence; Insulin Antibodies; Insulin Glargine; Insulin, Regular, Human; Recombinant Proteins

We compared changes in blood glucose (BG) and risk of hypoglycaemia during and after exercise in 40 patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) or insulin glargine (IGlar) in a randomized, open-label, two-period, crossover trial. After individual titration and a steady-state period, patients performed 30 min of moderate-intensity cycle ergometer exercise (65% peak rate of oxygen uptake). BG, counter-regulatory hormones and hypoglycaemic episodes were measured frequently during and for 24 h after exercise. BG changes during exercise were similar with IDeg and IGlar [estimated treatment difference (ETD) for maximum BG decrease: 0.14 mmol/l; 95% confidence interval (CI) -0.15, 0.42; p = 0.34], as was mean BG (ETD -0.16 mmol/l; 95% CI -0.36, 0.05; p = 0.13). No hypoglycaemic episodes occurred during exercise. Post-exercise mean BG, counter-regulatory hormone response and number of hypoglycaemic episodes in 24 h after starting exercise were similar with IDeg (18 events in 13 patients) and IGlar (23 events in 15 patients). This clinical trial showed that, in patients with T1D treated with a basal-bolus regimen, the risk of hypoglycaemia induced by moderate-intensity exercise was low with IDeg and similar to that with IGlar.

Topics: Adolescent; Adult; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Exercise Test; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Motor Activity; Risk; Young Adult

To investigate the differences in glycemic variability between the long-acting insulins glargine and degludec using continuous glucose monitoring, we conducted an open-label, multicenter, prospective, observational study that enrolled 21 participants with type 1 diabetes mellitus currently receiving basal-bolus insulin therapy with glargine. To avoid the potential influence of diet and exercise on glycemic control, all participants were housed and monitored within the hospital for the duration of the study. Once glycemic control was achieved with glargine, glycemic variability was evaluated using continuous glucose monitoring for 3 days. Glargine was then replaced by degludec and glycemic variability again assessed via continuous glucose monitoring. The primary outcome measure of mean amplitude of glycemic excursions was significantly reduced with degludec (p = 0.028), as was area under the curve for daily blood glucose level <70 mg/dL (p = 0.046). The required insulin dose was reduced up to 25% in the degludec group, although 24-h mean glucose concentrations were not different between groups. In conclusion, once or twice daily glargine was successfully replaced by a daily injection of degludec. When replacing glargine with degludec, a lower dose should be utilized to avoid hypoglycemia. Degludec is an effective and promising long-acting insulin that reduced hypoglycemia and daily blood glucose variability in participants with type 1 diabetes.

Topics: Adult; Aged; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

To evaluate the efficacy and safety of basal insulin peglispro (BIL) versus insulin glargine in patients with type 2 diabetes (hemoglobin A1c [HbA1c] ≤9% [75 mmol/mol]) treated with basal insulin alone or with three or fewer oral antihyperglycemic medications.. This 52-week, open-label, treat-to-target study randomized patients (mean HbA1c 7.42% [57.6 mmol/mol]) to BIL (n = 307) or glargine (n = 159). The primary end point was change from baseline HbA1c to 26 weeks (0.4% [4.4 mmol/mol] noninferiority margin).. At 26 weeks, reduction in HbA1c was superior with BIL versus glargine (-0.82% [-8.9 mmol/mol] vs. -0.29% [-3.2 mmol/mol]; least squares mean difference -0.52%, 95% CI -0.67 to -0.38 [-5.7 mmol/mol, 95% CI -7.3 to -4.2; P < 0.001); greater reduction in HbA1c with BIL was maintained at 52 weeks. More BIL patients achieved HbA1c <7% (53 mmol/mol) at weeks 26 and 52 (P < 0.001). With BIL versus glargine, nocturnal hypoglycemia rate was 60% lower, more patients achieved HbA1c <7% (53 mmol/mol) without nocturnal hypoglycemia at 26 and 52 weeks (P < 0.001), and total hypoglycemia rates were lower at 52 weeks (P = 0.03). At weeks 26 and 52, glucose variability was lower (P < 0.01), basal insulin dose was higher (P < 0.001), and triglycerides and aminotransferases were higher with BIL versus glargine (P < 0.05). Liver fat content (LFC), assessed in a subset of patients (n = 162), increased from baseline with BIL versus glargine (P < 0.001), with stable levels between 26 and 52 weeks.. BIL provided superior glycemic control versus glargine, with reduced nocturnal and total hypoglycemia, lower glucose variability, and increased triglycerides, aminotransferases, and LFC.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Male; Middle Aged

Advantages of continuous subcutaneous insulin infusion (CSII) over multiple daily injections with glargine (MDI/G) are still uncertain. We compared CSII vs. MDI/G therapy in unselected patients with type 1 diabetes using continuous glucose monitoring (CGSM). The primary end-points were glycaemic control and quality of life (QOL).. A total of 45 patients with long-term diabetes and mean HbA1c values of 8.6±1.8% (70.5±15.4mmol/mol), previously treated with MDI/NPH, were switched to MDI/G for 6 months and then, unfulfilling therapy CSII indication, were randomly assigned to CSII or MDI/G for another six months. We evaluated QOL (EsDqol) and glycaemic control by measuring HbA1c levels, rate of hypoglycaemia, ketoacidosis and CGSM data.. After the first phase (MDI/NPH to MDI/G) there was a significant improvement in total EsDQOL (99.72±18.38 vs. 92.07±17.65; p<0.028), a 0.5% decrease in HbA1c values (8.4±1.2 vs. 7.9±0.7% [68±9.7 vs. 63±5.5mmol/mol]; p<0.032), an improvement in glycaemic variability (standard deviation 66.9±14 vs. 59.4±16mg/dl; p<0.05), a decrease in insulin requirements (0.87±0.29 vs. 0.80±0.25U/kg; p<0.049), a decrease in number of severe hypoglycaemia episodes (0.44±0.9 vs. 0.05±0.2; p<0.014), and an increase in periods of normoglycaemia measured with CGSM (15.8±10.9% vs. 23±18.4%; p<0.003). Six months after randomization, significant improvements were seen in the HbA1c (7.9±0.7 vs. 7±0.6% [63±5.5 vs. 53±4.5mmol/mol]; p<0.001) and EsQOL (91.66±22 vs. 84.53±1.63; p<0.045) only in the CSII group. The HbA1c value was significantly lower when compared with the MDI/G group (CSII 7±0.6% [53±4.5mmol/mol] vs. MDI/G 7.6±0.9% [59.6±7.7mmol/mol]; p<0.03).. Intensive insulin therapy with CSII vs. MDI/G was associated with better levels of HbA1c in patients with long-term type 1 diabetes.

Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Complications; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Subcutaneous; Injections, Subcutaneous; Insulin Glargine; Insulin Lispro; Male; Meals; Middle Aged; Quality of Life; Treatment Outcome; Young Adult

To compare the efficacy and safety of insulin glargine 300 U/ml (Gla-300) with glargine 100 U/ml (Gla-100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)].. The EDITION JP 2 study (NCT01689142) was a 6-month, multicentre, open-label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m(2), mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla-300 or Gla-100, while continuing OAD(s). Basal insulin was titrated to target fasting self-monitored plasma glucose 4.4-5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change.. Gla-300 was non-inferior to Gla-100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] -0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla-300 and Gla-100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla-300 versus Gla-100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between-treatment difference in weight change favoured Gla-300 [LS mean difference -1.0 (95% CI -1.5, -0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups.. Japanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla-300 than with Gla-100, while glycaemic control did not differ.

Topics: Administration, Oral; Aged; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Japan; Male; Middle Aged; Risk

To compare efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of insulin glargine 100 U/ml (Gla-100) in Japanese adults with type 1 diabetes.. The EDITION JP 1 study (NCT01689129) was a 6-month, multicentre, open-label, phase III study. Participants (n = 243) were randomized to Gla-300 or Gla-100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self-monitored plasma glucose target of 4.4-7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight.. Gla-300 was non-inferior to Gla-100 for the primary endpoint of HbA1c change over the 6-month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) -0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla-300 than with Gla-100 at night [rate ratio 0.66 (95 % CI 0.48-0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65-0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla-300 0.35 U/kg/day, Gla-100 0.29 U/kg/day). A between-treatment difference in body weight change over 6 months favouring Gla-300 was observed [LS mean difference -0.6 kg (95 % CI -1.1 to -0.0); p = 0.035]. Adverse event rates were comparable between the groups.. In Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycaemic control did not differ.

Topics: Adult; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Japan; Male; Middle Aged; Risk

The safety and efficacy of LY2963016 insulin glargine (LY IGlar) and Lantus insulin glargine (IGlar), products with identical primary amino acid sequences, were assessed in subgroups of patients with type 1 (T1D, n = 452) or type 2 diabetes (T2D, n = 299) reporting prestudy IGlar treatment in 52-week open-label (ELEMENT-1) and 24-week double-blind (ELEMENT-2) studies. At randomization, patients transitioned from their prestudy IGlar to equivalent doses of LY IGlar or IGlar. Primary efficacy (change in glycated haemoglobin from baseline to 24 weeks), other efficacy and select safety outcomes of LY IGlar were compared with those of IGlar. Continuous data were analysed using analysis of covariance, categorical data by Fisher's exact test, and treatment comparisons for hypoglycaemia by Wilcoxon test. No statistically significant treatment differences were identified for efficacy and safety outcomes except for weight change (T1D), overall incidence of detectable insulin antibodies (T2D), and serious adverse events (T2D). These differences were neither consistently observed across both studies nor observed in the total study populations, and their magnitude suggests they were not clinically meaningful. LY IGlar and IGlar show similar efficacy and safety profiles in patients reporting prestudy IGlar treatment.

Topics: Biosimilar Pharmaceuticals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

Previous studies comparing insulin detemir versus insulin glargine showed conflicting results, and included only outpatients. This study compared the two insulin analogs once daily in hospitalized patients with type 2 diabetes (T2D).. A total of 55 patients aged 18-80 years with hyperglycemia admitted to the endocrinology wards were screened between June 2014 and February 2015. Forty-two enrolled patients were randomly assigned to receive either insulin detemir followed by insulin glargine once daily (n = 21), or vice versa (n = 21). The two insulin analogs were titrated 0.1 U/kg once daily based on fasting blood glucose (FBG). After achieving FBG <7.8 mmol/L (the first period), subjects were switched from one analog to the other (the second period) with no change in the dose. The second period lasted for 3 days. When hypoglycemia occurred in the second period, the observation was discontinued. Six-point blood glucose including FBG, 2 h after breakfast, lunch, dinner, bedtime, and at 3:00 am was tested every day. The glucose profiles of the final days in the two periods were compared.. At the end of the first period, days for achieving FBG target (4.0 ± 0.5 days vs. 3.3 ± 0.4 days, t = 1.079, P = 0.286) and total daily dose (30.1 ± 2.4 U vs. 30.1 ± 2.9 U, t = 0.002, P = 0.999) between insulin detemir and insulin glargine were similar. There was no significant difference in the 24-h glucose control between the two analogs. No hypoglycemia occurred with both analogs in the first period. However, in the second period, when insulin glargine was switched to insulin detemir, two, three and, one patients had hypoglycemia events on day 1, day 2 and day 3 of the second period, respectively. One patient had severe hypoglycemia on day 1.. When both basal insulin analogs were given once daily in T2D, insulin detemir achieved similar efficacy to insulin glargine. On the other hand, there may be differences in action of the compared basal insulins. Further studies with larger patient samples are necessary to support evidence and reveal possible mechanisms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Young Adult

Insulin glargine 300 U/mL (Gla-300) has a more constant and prolonged action profile than insulin glargine 100 U/mL and in clinical studies is associated with similar glycemic control but less hypoglycemia. Whether its effects are altered by variability of injection time was examined in two 3-month substudies.. Eligible participants completing 6 months of optimized treatment with Gla-300 in EDITION 1 (n = 109) and EDITION 2 (n = 89), having a mean hemoglobin A1c (HbA1c) level of 7.3 % (SD 1.0 %), were randomized (1:1) to groups advised to increase variability of between-injection intervals to 24 ± up to 3 h or to maintain fixed 24-h intervals for 3 months. Changes of HbA1c level and other efficacy and safety measures were assessed.. In the fixed-dosing group, 64% of participants reported all intervals within the 23-25-h range, compared with 15% of those advised flexible dosing. In the fixed- and flexible-dosing groups, 12% and 41%, respectively, of between-injection intervals were outside the 23-25-h range, and 2% and 16%, respectively, were outside the 21-27-h range. Least squares mean between-group difference in HbA1c change from baseline was 0.05 % (95% confidence interval [CI], -0.13 to 0.23); for fasting plasma glucose, 2.7 mg/dL (95% CI, -9.0 to 14.4); and for daily basal insulin dose, 0.00 U/kg (95% CI, -0.02 to 0.03). Frequencies of hypoglycemia and adverse events did not differ between groups.. The efficacy and safety of Gla-300 demonstrated in EDITION 1 and EDITION 2 are maintained in substudies when the insulin was injected up to 3 h before or after the usual time of administration.

Topics: Activities of Daily Living; Administration, Oral; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Intention to Treat Analysis; Male; Meals; Medication Adherence

To describe the efficacy and safety of premixed insulin lispro protamine suspension 75%/insulin lispro solution 25% (LM25) twice daily (bid) versus basal insulin glargine plus prandial insulin lispro (IGL), both once daily, according to main meal timing.. Data were obtained post hoc from a 24 week, randomized, open-label study comparing LM25 and IGL as insulin intensification in patients with type 2 diabetes inadequately controlled with once daily basal insulin glargine plus metformin and/or pioglitazone (ClinicalTrials.gov identifier: NCT01175824). Patients administered LM25 bid before breakfast and the evening meal, insulin glargine at bedtime and insulin lispro before the day's main meal (meal with the highest 2 hour postprandial glucose level during screening). Patients were grouped by main meal. Changes in glycosylated hemoglobin (HbA1c) and bodyweight were summarized using likelihood-based mixed models; hypoglycemia incidence was compared between treatments using Fisher's exact test.. Overall, 476 patients (LM25, n = 236; IGL, n = 240) were randomized. In all main meal groups, with both insulin regimens, mean HbA1c significantly decreased from baseline to 24 weeks (p < 0.0001). Patients whose main meal was in the evening had a greater bodyweight increase with LM25 than with IGL (p = 0.015), and a smaller proportion of these patients experienced total (p = 0.027) and nocturnal (p = 0.006) hypoglycemia with LM25 compared with IGL. Patients whose main meal was lunch experienced more nocturnal hypoglycemia with LM25 than with IGL (p = 0.030). Study limitations include that this was a post hoc analysis and no assessments ensured that: SMBG results determined timing of the main meal, each patient's main meal remained unchanged throughout the study, or patients administered insulin lispro with that meal.. Glycemic control improved in patients receiving either LM25 or IGL, irrespective of main meal timing. Both regimens can be used in patients with inadequate glycemic control who are in need of insulin intensification.

Topics: Aged; Blood Glucose; Clinical Protocols; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin Lispro; Likelihood Functions; Male; Meals; Middle Aged; Postprandial Period; Weight Gain

Achieving glycemic control remains a challenge for patients with type 2 diabetes, even with insulin therapy.. To assess whether a fixed ratio of insulin degludec/liraglutide was noninferior to continued titration of insulin glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin.. Phase 3, multinational, multicenter, 26-week, randomized, open-label, 2-group, treat-to-target trial conducted at 75 centers in 10 countries from September 2013 to November 2014 among 557 patients with uncontrolled diabetes treated with glargine (20-50 U) and metformin (≥1500 mg/d) with glycated hemoglobin (HbA1c) levels of 7% to 10% and a body mass index of 40 or lower.. 1:1 randomization to degludec/liraglutide (n = 278; maximum dose, 50 U of degludec/1.8 mg of liraglutide) or glargine (n = 279; no maximum dose), with twice-weekly titration to a glucose target of 72 to 90 mg/dL.. Primary outcome measure was change in HbA1c level after 26 weeks, with a noninferiority margin of 0.3% (upper bound of 95% CI, <0.3%). If noninferiority of degludec/liraglutide was achieved, secondary end points were tested for statistical superiority and included change in HbA1c level, change in body weight, and rate of confirmed hypoglycemic episodes.. Among 557 randomized patients (mean: age, 58.8 years; women, 49.7%), 92.5% of patients completed the trial and provided data at 26 weeks. Baseline HbA1c level was 8.4% for the degludec/liraglutide group and 8.2% for the glargine group. HbA1c level reduction was greater with degludec/liraglutide vs glargine (-1.81% for the degludec/liraglutide group vs -1.13% for the glargine group; estimated treatment difference [ETD], -0.59% [95% CI, -0.74% to -0.45%]), meeting criteria for noninferiority (P < .001), and also meeting criteria for statistical superiority (P < .001). Treatment with degludec/liraglutide was also associated with weight loss compared with weight gain with glargine (-1.4 kg for degludec/liraglutide vs 1.8 kg for glargine; ETD, -3.20 kg [95% CI, -3.77 to -2.64],P < .001) and fewer confirmed hypoglycemic episodes (episodes/patient-year exposure, 2.23 for degludec/liraglutide vs 5.05 for glargine; estimated rate ratio, 0.43 [95% CI, 0.30 to 0.61],P < .001). Overall and serious adverse event rates were similar in the 2 groups, except for more nonserious gastrointestinal adverse events reported with degludec/liraglutide (adverse events, 79 for degludec/liraglutide vs 18 for glargine).. Among patients with uncontrolled type 2 diabetes taking glargine and metformin, treatment with degludec/liraglutide compared with up-titration of glargine resulted in noninferior HbA1c levels, with secondary analyses indicating greater HbA1c level reduction after 26 weeks of treatment. Further studies are needed to assess longer-term efficacy and safety.. clinicaltrials.gov Identifier: NCT01952145.

Topics: Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Weight Gain; Weight Loss

To lower the barrier for initiating insulin treatment and obtain adequate glycemic control in type 2 diabetes mellitus (T2DM), new basal insulin preparations with improved pharmacological properties and consequently a lower risk of hypoglycemia are needed. The objective of this trial was to confirm the efficacy and compare the safety of insulin degludec (IDeg) with insulin glargine (IGlar) in a multinational setting with two thirds of subjects enrolled in China.. This was a 26-week, randomized, open-label, parallel-group, treat-to-target, non-inferiority trial in 833 subjects with T2DM (48 % were female, mean age 56 years, diabetes duration 8 years), inadequately controlled on oral antidiabetic drugs (OADs). Subjects were randomized 2:1 to once-daily IDeg (555 subjects) or IGlar (278 subjects), both with metformin. The primary endpoint was the change from baseline in glycosylated hemoglobin (HbA1c) after 26 weeks.. The completion rate was high (IDeg 94.2 %; IGlar 91.4 %). Mean HbA1c decreased from 8.3 to 7.0 % in both groups. Estimated treatment difference (ETD) [95 % confidence interval (CI)] IDeg-IGlar in change from baseline was -0.05 % points [-0.18 to 0.08], confirming the non-inferiority of IDeg to IGlar. The proportion of subjects achieving HbA1c <7.0 % was 54.2 and 51.4 % with IDeg and IGlar, respectively (estimated odds ratio [95 % CI] IDeg/IGlar: 1.14 [0.84 to 1.54]). The mean decrease in fasting plasma glucose, self-measured plasma glucose profiles, and insulin dose were similar between groups. Numerically lower rates of overall (estimated rate ratio [95 % CI] IDeg/IGlar: 0.80 [0.59 to 1.10]) and nocturnal (0.77 [0.43 to 1.37]) confirmed hypoglycemia were observed with IDeg compared with IGlar. No treatment differences in other safety parameters were found. Subjects were more satisfied with the IDeg device compared with the IGlar device as reflected by the total Treatment Related Impact Measures-Diabetes Device score (ETD [95 % CI] IDeg-IGlar: 2.2 [0.2 to 4.3]).. IDeg provided adequate glycemic control non-inferior to IGlar and a tendency for a lower hypoglycemia rate. IDeg is considered suitable for initiating insulin therapy in T2DM patients on OADs requiring intensified treatment.. Clinicaltrials.gov NCT01849289.

Topics: Blood Glucose; China; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Treatment Outcome

To provide evidence-based options on how to intensify basal insulin, we explored head-to-head prandial interventions in overweight patients with type 2 diabetes inadequately controlled on basal insulin glargine with or without 1-3 oral antidiabetic agents (OADs).. Patients were randomized to lixisenatide once daily or insulin glulisine given once or thrice daily, added to glargine, with or without metformin, if HbA1c remained ≥7 to ≤9% (≥53 to ≤75 mmol/mol) after 12 weeks of glargine optimization with OADs other than metformin stopped at the start of optimization. Coprimary end points at 26 weeks were 1) noninferiority (95% CI upper bound <0.4% [<4.4 mmol/mol]) in HbA1c reduction with lixisenatide versus glulisine once daily, and either 2a) noninferiority in HbA1c reduction for lixisenatide versus glulisine thrice daily or 2b) superiority in body weight change for lixisenatide versus glulisine thrice daily. Fasting and postprandial plasma glucose, composite efficacy/safety end points, and adverse events were also assessed.. Baseline characteristics were similar between arms (n = 298, diabetes and basal insulin duration of 12.2 and 3.2 years, respectively; BMI 32.2 kg/m(2)). HbA1c improved from 8.5% to 7.9% (69 to 63 mmol/mol) with glargine optimization and further to 7.2%, 7.2%, and 7.0% (55, 55, and 53 mmol/mol) with lixisenatide and glulisine once daily and thrice daily, respectively; all coprimary end points were met. Symptomatic hypoglycemia and body weight were lower in lixisenatide versus glulisine patients. More gastrointestinal events occurred with lixisenatide.. Short-acting glucagon-like peptide-1 receptor agonists as add-on to basal insulin may become a preferred treatment intensification option, attaining meaningful glycemic targets with fewer hypoglycemic events without weight gain versus basal-plus or basal-bolus in uncontrolled basal insulin-treated type 2 diabetes.

Topics: Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endpoint Determination; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Meals; Metformin; Middle Aged; Overweight; Peptides; Postprandial Period

Topics: Aged; Aged, 80 and over; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Treatment Outcome

This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 μg lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naïve type 2 diabetes on metformin.. Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 μg and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI ≤0.4%) of LixiLan in reducing HbA1c; if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety.. Baseline characteristics (mean age 57 years, diabetes duration 6-7 years, BMI 32 kg/m(2)) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squared mean [95% CI] difference: -0.17% [-0.31, -0.04] {-1.9 mmol/mol [-3.4, -0.4]}; P = 0.01). HbA1c <7.0% (<53 mmol/mol) was achieved in 84% and 78% of participants (nonsignificant), respectively. LixiLan improved 2-h postmeal plasma glucose versus Gla-100 (least-squared mean difference: -3.17 mmol/L [-57 mg/dL]; P < 0.0001). Body weight was reduced with LixiLan (-1 kg) and increased with Gla-100 (+0.5 kg; P < 0.0001), with no increase in hypoglycemic events (∼25% in each group). The incidence of nausea (7.5%) and vomiting (2.5%) was low with LixiLan.. LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Middle Aged; Peptides; Postprandial Period; Risk; Safety

The primary objective was to demonstrate that basal insulin peglispro (BIL) was non-inferior compared with insulin glargine (GL) for haemoglobin A1c (HbA1c) at 26 weeks with a non-inferiority margin of 0.4%.. IMAGINE 1 was a Phase 3, open-label, parallel-arm study conducted in nine countries. Adults with type 1 diabetes (n = 455) were randomized (2:1) to bedtime BIL or GL in combination with prandial insulin lispro for 78 weeks, with a primary endpoint of 26 weeks. An electronic diary facilitated data capture and insulin dosing calculations for intensive insulin management.. At 26 weeks, mean HbA1c was 7.06% ± 0.04% and 7.43% ± 0.06% for patients assigned to BIL (N = 295) and GL (N = 160), respectively (difference -0.37% [95% CI: -0.50 to -0.23], P < .001); more patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P < .001). Compared with GL, patients using BIL lost weight, with lower fasting serum glucose and between-day fasting blood glucose variability, and 36% less nocturnal hypoglycemia, 29% more total hypoglycemia and more severe hypoglycemia. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations ≥3 × ULN. BIL treatment was associated with more frequent injection site reactions and an increase from baseline in serum triglycerides.. In patients with type 1 diabetes, treatment with BIL compared to GL for 26 weeks was associated with lower HbA1c, less nocturnal hypoglycemia, lower glucose variability and weight loss. Increases in total and severe hypoglycemia, triglycerides, aminotransferases and injection site reactions were also noted.

Topics: Adult; Alanine Transaminase; Blood Glucose; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Insulin Lispro; Male; Meals; Middle Aged; Polyethylene Glycols; Severity of Illness Index; Treatment Outcome; Weight Loss; Young Adult

Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action, resulting from reduced peripheral effects. This report summarizes hypoglycaemia data from five BIL phase III studies with insulin glargine as the comparator, including three double-blind trials. Prespecified pooled analyses (n = 4927) included: patients with type 2 diabetes (T2D) receiving basal insulin only, those with T2D on basal-bolus therapy, and those with type 1 diabetes (T1D). BIL treatment resulted in a 36-45% lower nocturnal hypoglycaemia rate compared with glargine, despite greater reduction in glycated haemoglobin (HbA1c) and higher basal insulin dosing. The total hypoglycaemia rate was similar in patients with T2D on basal treatment only, trended towards being higher (10%) in patients with T2D on basal-bolus treatment (p = .053), and was 15% higher (p < .001) with BIL versus glargine in patients with T1D, with more daytime hypoglycaemia in the T1D and T2D groups who were receiving basal-bolus therapy. In T1D, during the maintenance treatment period (26-52 weeks), the total hypoglycaemia rate was not significantly different. There were no differences in severe hypoglycaemia in the T1D or T2D pooled analyses. BIL versus glargine treatment resulted in greater HbA1c reduction with less nocturnal hypoglycaemia in all patient populations, higher daytime hypoglycaemia with basal-bolus therapy in the T1D and T2D groups, and an associated increase in total hypoglycaemia in the patients with T1D.

Topics: Adult; Aged; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Glargine; Insulin Lispro; Male; Middle Aged; Polyethylene Glycols; Retrospective Studies

To compare glucose variability in patients with type 1 diabetes (T1D) treated with insulin glargine (IGla) versus insulin degludec (IDeg) using continuous glucose monitoring (CGM).. Thirteen patients with T1D were randomly assigned to receive IDeg once-daily followed by IGla twice-daily or vice versa. They were evaluated for glucose variability by CGM after >4weeks of treatment with either insulin, and then were crossed over to the other, and evaluated by CGM after >4weeks.. The total daily insulin dose (TDD) (U/kg/day) and the total daily basal insulin dose (U/kg/day) in the patients were significantly lower while taking IDeg than while taking IGla (mean [95% confidence interval] 0.72 [0.61-0.83] vs. 0.76 [0.64-0.88]; P=0.001, 0.29 [0.22-0.36] vs. 0.33 [0.26-0.40]; P=0.001), although no significant difference was noted in the patients while on IDeg versus while on IGla in 24-h mean glucose and SDs of 24-h glucose. Again, the range of postprandial glucose increase was not significantly different between the meals in the patients while taking IDeg (P=0.288) but significantly different in the patients while taking IGla (P=0.033).. The use of once-daily IDeg leads not only to similar glycemic control to that seen with twice-daily IGla even in those who received IGla prior to the study, but also to significant decreases in TDD and long-acting basal insulin dose.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Pilot Projects; Prognosis

DEVOTE was designed to evaluate the cardiovascular safety of insulin degludec (IDeg) vs insulin glargine U100 (IGlar) in patients with T2D at high risk of cardiovascular events. DEVOTE is a phase 3b, multicenter, international, randomized, double-blind, active comparator-controlled trial, designed as an event-driven trial that would continue until 633 positively adjudicated primary events were accrued. The primary end point was the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Patients with T2D at high risk of cardiovascular complications were randomized 1:1 to receive either IDeg or IGlar, each added to background therapies. This trial was designed to demonstrate statistical noninferiority of IDeg vs IGlar for the primary end point. DEVOTE enrolled 7,637 patients between October 2013 and November 2014 at 436 sites in 20 countries. Of these, 6,506 patients had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. DEVOTE was designed to provide conclusive evidence regarding the cardiovascular safety of IDeg relative to IGlar in a high-risk population of patients with T2D.

Topics: Aged; Angina, Unstable; Cardiovascular Diseases; Comorbidity; Coronary Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Stroke

This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia.. Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites.. Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost.. www.clinicaltrials.gov identifier is NCT02451137.

Topics: Aged; Blood Glucose; Body Weight; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Health Services; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Patient Reported Outcome Measures; United States

Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D.. This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin.. After 30weeks, addition of exenatide BID or insulin lispro resulted in significant (P<0.0001) reductions in HbA1c (exenatide BID: -0.9% [-10mmol/mol]; insulin lispro: -1.2% [-13mmol/mol]). Weight was stable in the exenatide BID group (-0.1kg) and increased significantly (+3.4kg; P<0.0001) with insulin lispro. Major and minor hypoglycemia occurred less frequently (40 vs. 253 events) with exenatide BID compared with insulin lispro. Gastrointestinal adverse events of nausea, diarrhea, and vomiting occurred more frequently with exenatide BID than with insulin lispro.. Both exenatide BID and prandial insulin lispro, each added to basal insulin glargine, were effective at reducing HbA1c in Latin American patients. Treatment with exenatide BID resulted in stable weight but more gastrointestinal adverse events. Treatment with insulin lispro resulted in weight gain and an increased risk of hypoglycemia. These findings support the addition of exenatide BID to insulin glargine as an option for Latin American patients unable to achieve glycemic control on basal insulin alone.

Topics: Adult; Aged; Argentina; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Male; Metformin; Mexico; Middle Aged; Peptides; Retrospective Studies; Treatment Outcome; United States; Venoms

To evaluate the efficacy and safety of insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in adults with type 1 diabetes in Japan over 12months.. EDITION JP 1 was a multicentre, randomised, open-label phase 3 study. Following a 6-month on-treatment period, participants continued to receive Gla-300 or Gla-100 once daily, plus mealtime insulin, over a 6-month open-label extension phase. HbA1c, hypoglycaemia, body weight and adverse events were assessed.. Overall, 114/122 (93%) and 114/121 (94%) of participants in the Gla-300 and Gla-100 group, respectively, completed the 6-month extension phase. Glycaemic control was sustained in both groups up to month 12 (mean HbA1c: Gla-300, 7.9% [62mmol/mol]; Gla-100, 7.8% [62mmol/mol]). Annualised rates of hypoglycaemia were lower with Gla-300 versus Gla-100; significantly for nocturnal confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia (2.39 and 3.85 events per participant-year; rate ratio: 0.62 [0.39-0.97]). No between-treatment differences in mean body weight change or adverse events were observed.. Over 12months' treatment, participants with type 1 diabetes receiving Gla-300 achieved sustained glycaemic control and experienced less nocturnal hypoglycaemia that was confirmed (<3.0mmol/L [<54mg/dL]) or severe compared with Gla-100, supporting the 6-month results.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Time Factors

Insulin therapy should be strongly considered in newly diagnosed type 2 diabetic (T2D) patients with severe hyperglycemia. However, whether insulin be continued or patients switched to an oral antidiabetic drug (OAD) after short-term intensive insulin therapy (ITT) is not clear.. After ITT for 10-14 days, 47 patients were randomized into either a glargine (n = 21) or metformin-based OAD (n = 26) group for a 6-month intervention. After these 6 months, patients in the glargine group were switched to metformin-based OAD therapy, whereas treatment in the OAD group was unchanged. Patients were followed-up for another 6 months.. At the end of the 6-month intervention, HbA1c was similarly reduced in both the glargine (from 11.81 ± 1.70% to 6.48 ± 0.79%; P < 0.001) and OAD (from 11.71 ± 1.89% to 6.16 ± 0.52%; P < 0.001) groups. At the end of 12 months, HbA1c was at comparable and near optimal levels in both groups. Similar increases were seen in homeostatic model assessment of β-cell function in the two groups after 6 months. There were no significant differences between the two groups in insulin sensitivity improvement, hypoglycemic episodes, weight change, treatment satisfaction and quality of life after the 6-month intervention.. The effects of metformin-based OAD therapy on glycemic control and improvements in β-cell function are not inferior to glargine in newly diagnosed T2D patients with severe hyperglycemia after short-term ITT. Considering the superiority of metformin in terms of safety, cost, and convenience, metformin-based OAD therapy is strongly recommended for these patients.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; China; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Secreting Cells; Insulin, Long-Acting; Male; Metformin; Middle Aged; Prognosis; Quality of Life; Risk Factors

To examine whether insulin glargine can lead to better control of glycated haemoglobin (HbA1c) than that achieved by neutral protamine Hagedorn (NPH) insulin, using a protocol designed to limit nocturnal hypoglycaemia.. The present study, the Least One Oral Antidiabetic Drug Treatment (LANCELOT) Study, was a 36-week, randomized, open-label, parallel-arm study conducted in Europe, Asia, the Middle East and South America. Participants were randomized (1:1) to begin glargine or NPH, on background of metformin with glimepiride. Weekly insulin titration aimed to achieve median prebreakfast and nocturnal plasma glucose levels ≤5.5 mmol/l, while limiting values ≤4.4 mmol/l.. The efficacy population (n = 701) had a mean age of 57 years, a mean body mass index of 29.8 kg/m², a mean duration of diabetes of 9.2 years and a mean HbA1c level of 8.2% (66 mmol/mol). At treatment end, HbA1c values and the proportion of participants with HbA1c <7.0 % (<53 mmol/mol) were not significantly different for glargine [7.1 % (54 mmol/mol) and 50.3%] versus NPH [7.2 % (55 mmol/mol) and 44.3%]. The rate of symptomatic nocturnal hypoglycaemia, confirmed by plasma glucose ≤3.9 or ≤3.1 mmol/l, was 29 and 48% less with glargine than with NPH insulin. Other outcomes were similar between the groups.. Insulin glargine was not superior to NPH insulin in improving glycaemic control. The insulin dosing algorithm was not sufficient to equalize nocturnal hypoglycaemia between the two insulins. This study confirms, in a globally heterogeneous population, the reduction achieved in nocturnal hypoglycaemia while attaining good glycaemic control with insulin glargine compared with NPH, even when titrating basal insulin to prevent nocturnal hypoglycaemia rather than treating according to normal fasting glucose levels.

Topics: Aged; Asia; Blood Glucose Self-Monitoring; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Drug Resistance; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Middle East; South Africa; Sulfonylurea Compounds

Hypoglycemia is a leading risk of glucose-lowering therapy. Treatment with insulin glargine compared with standard care early in the course of dysglycemia in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial provides information on the frequency and predictors of hypoglycemia in this setting.. A total of 12,537 people with high cardiovascular risk and dysglycemia treated with one or no oral glucose-lowering agents were randomized to add glargine titrated to a fasting glucose level of ≤5.3 mmol/L (≤95 mg/dL) or to use standard therapies. Independent associations of both nonsevere hypoglycemia (symptomatic and confirmed with a glucose level of ≤3 mmol/L [≤54 mg/dL]) and severe hypoglycemia with characteristics at baseline, treatment allocation, and average HbA1c were assessed by Cox proportional hazards models.. During a median follow-up period of 6.2 years, 28% of participants reported nonsevere hypoglycemia, and 3.8% reported severe hypoglycemia. Prior use of a sulfonylurea and allocation to glargine independently predicted a higher risk for both categories of participants. Nonsevere events were independently associated with younger age, lower BMI, the presence of diabetes, and higher baseline HbA1c level. Severe events were associated with older age, hypertension, higher serum creatinine level, and lower cognitive function, but not baseline glycemic status. Progressively higher on-treatment HbA1c level was associated with a lower risk of nonsevere events in both treatment groups; a lower risk of severe events in the glargine group, and a higher risk of severe events with standard care.. Hypoglycemia was relatively uncommon in the ORIGIN trial, but was more frequent with sulfonylurea use at baseline and allocation to glargine. Nonsevere and severe events were associated with different clinical characteristics, awareness of which may guide individualized therapy.

Topics: Aged; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Proportional Hazards Models; Risk Factors; Sulfonylurea Compounds

The study presents a comparison of the glucose-lowering effects, glycemic variability, and insulin doses during treatment with insulin degludec or insulin glargine.. In this open-label, single-center, 2-way crossover study, 13 Japanese diabetic outpatients in the insulin-dependent state on basal-bolus therapy were assigned to receive either insulin glargine followed by insulin degludec, or insulin degludec followed by insulin glargine. Basal insulin doses were fixed in principle, and patients self-adjusted their bolus insulin doses. Seventy-two-hour continuous glucose monitoring was performed 2 weeks after switching the basal insulin.. Mean blood glucose (mg/dL) was not significantly different between insulin degludec and insulin glargine over 48 hours (141.8 ± 35.2 vs 151.8 ± 43.3), at nighttime (125.6 ± 40.0 vs 124.7 ± 50.4), or at daytime (149.3 ± 37.1 vs 163.3 ± 44.5). The standard deviation (mg/dL) was also similar (for 48 hours: 48.9 ± 19.4 vs 50.3 ± 17.3; nighttime: 18.7 ± 14.3 vs 13.7 ± 6.7; daytime: 49.3 ± 20.0 vs 44.3 ± 17.7). Other indices of glycemic control, glycemic variability, and hypoglycemia were similar for both insulin analogs. Total daily insulin dose (TDD) and total daily bolus insulin dose (TDBD) were significantly lower with insulin degludec than with insulin glargine (TDD: 0.42 ± 0.20 vs 0.46 ± 0.22 U/kg/day, P = .028; TDBD: 0.27 ± 0.13 vs 0.30 ± 0.14 U/kg/day, P = .036).. Insulin degludec and insulin glargine provided effective and stable glycemic control. Insulin degludec required lower TDD and TDBD in this population of patients.

Topics: Asian People; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of glargine 100 U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs.. The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4-5.6 mmol/l (80-100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed.. Randomized participants (n = 878) had a mean (standard deviation) age of 57.7 (10.1) years, diabetes duration 9.8 (6.4) years, body mass index 33.0 (6.7) kg/m(2) and HbA1c 8.54 (1.06) % [69.8 (11.6) mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) -0.09 to 0.17] % or 0.4 (-1.0 to 1.9) mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified.. Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk.

Topics: Administration, Oral; Aged; Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Resistance; Europe; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Japan; Male; Middle Aged; North America; Risk; Weight Gain

To compare the effectiveness and safety of two glycemic control regimens in stable critical care patients receiving parenteral nutrition (PN).. Prospective, randomized open-label clinical trial.. Eligible postoperative critical care patients in the ICU began PN on the first to the seventh day of ICU admission. The PN admixture included regular insulin, in doses sufficient to maintain 3 or more goal blood glucose (BG) levels between 110 and 180 mg/dl. After 3 to 5 days of PN containing regular insulin, patients were randomized to 3 more days of regular insulin at the same dose or 80% of their total daily regular insulin dose provided in PN solution as glargine insulin. Capillary BG monitoring was performed every 6 hours.. Twenty one patients were randomized to each treatment group. Median APACHE II scores were not significantly different between the two groups within the first 24-hour of ICU admission. There were no significant differences between the two groups at day 3 for mean daily dextrose (306.9 ± 46.2 vs. 305.2 ± 52.2 g; p=0.913) or insulin (18.3 ± 8.8 vs. 19.5 ± 10.0 units; p=0.696) doses. The percentage of BG values in the goal (110-180 mg/dl), hyperglycemic (> 180 mg/dl), and hypoglycemic (< 70 mg/dl) BG levels were similar between the two groups (69.0% vs. 66.7%, p=0.567; 11.9% vs. 11.1%, p=0.780; 0% vs. 1.6%, p=0.124, respectively). Mean daily BG levels were not significantly different between the two groups on each of the 3 study days (day 1: 140 ± 20 vs. 131 ± 25 mg/dl, p=0.194; day 2: 136 ± 20 vs. 140 ± 18 mg/dl, p=0.498; day 3: 142 ± 15 vs. 140 ± 19 mg/dl; p=0.741).. These data suggest that, compared with regular insulin added to PN, glargine insulin results in similar glycemic control and rates of hyperglycemia and hypoglycemia in stable critical care patients.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Critical Care; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Intensive Care Units; Male; Parenteral Nutrition; Prospective Studies

To compare, using a continuous glucose monitoring (CGM) system, the effect on glycaemic variability of insulin glargine, detemir and lispro protamine.. A total of 49 white people with type 1 diabetes, not well controlled by three times daily insulin lispro, taken for at least 2 months before study and on a stable dose, were enrolled. The study participants were randomized to add insulin glargine, detemir or lispro protamine, once daily, in the evening. We used a CGM system, the iPro Digital Recorder (Medtronic MiniMed, Northridge, CA, USA) for 1 week. Glycaemic control was assessed according to mean blood glucose values, the area under the glucose curve above 3.9 mmol/l (AUC(>3.9)) or above 10.0 mmol/l (AUC(>10.0)), and the percentage of time spent with glucose values >3.9 or >10.0 mmol/l. Intraday glycaemic variability was assessed using standard deviation (s.d.) values, the mean amplitude of glycaemic excursions and continuous overlapping of net glycaemic action. Day-to-day glycaemic variability was assessed using the mean of daily differences.. The s.d. was found to be significantly lower with insulin lispro protamine and glargine compared with insulin detemir. AUC(>3.9) was higher and AUC(>10.0) was lower with insulin lispro protamine and glargine compared with detemir. The mean amplitude of glycaemic excursions and continuous overlapping net glycaemic action values were lower with insulin lispro protamine and glargine compared with detemir. In addition, the mean of daily differences was significantly lower with insulin lispro protamine and glargine compared with detemir. Fewer hypoglycaemic events were recorded during the night-time with insulin lispro protamine compared with glargine and detemir.. The results suggest that insulin lispro protamine and glargine are more effective than detemir in reducing glycaemic variability and improving glycaemic control in people with type 1 diabetes. Insulin lispro protamine seems to lead to fewer hypoglycaemic events than other insulin regimens.

Topics: Adult; Analysis of Variance; Area Under Curve; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin Lispro; Male; Young Adult

Hypoglycemia is a barrier to the achievement of glycemic targets and limits the beneficial effects of improved glucose control on cardiovascular outcomes in type 2 diabetes (T2D). Circulating endothelial progenitor cells (EPCs) participate in cardiovascular homeostasis and predict future cardiovascular events. Therefore, we herein analyzed the association between occurrence of hypoglycemia and EPC changes in T2D patients after optimization of glucose control with basal insulin therapy.. In the NCT00699686 trial, 42 T2D insulin-naïve patients received a 3 + 3-month cross-over therapy with glargine and detemir. There were 43 minor and 2 severe hypoglycemic episodes in 19 patients (45.2 %, 0.54 episodes/patient/year). Changes in EPCs were analyzed in relation to the occurrence of hypoglycemia during the trial.. Patients with hypoglycemia had a higher final HbA1c at 6 months than patients without, although absolute HbA1c changes were not significantly different. Though PCs increased at study end, in patients experiencing at least 1 hypoglycemic episode, the changes in CD34(+), CD133(+) progenitor cells and CD34(+)KDR(+) EPCs were significantly lower than the respective changes in patients without incident hypoglycemia, even after correcting for confounders. During treatment with detemir, which induced >twofold less hypoglycemia than glargine, CD34(+)KDR(+) EPCs increased significantly more than during treatment with glargine.. In naïve T2D patients initiating basal insulin, hypoglycemia prevents the increase in vasculoprotective PCs. Clinically, these data strengthen the importance of avoiding hypoglycemia to improve cardiovascular outcomes during the treatment of T2D.

Topics: Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelial Progenitor Cells; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged

Patients with type 1 diabetes face heightened risk of hypoglycemia after exercise. Subsequent overfeeding, as a preventative measure against hypoglycemia, negates the energy deficit after exercise. Patients are also required to reduce the insulin dose administered with postexercise foods to further combat hypoglycemia. However, the insulin dose is dictated solely by the carbohydrate content, even though postprandial glycemia is vastly influenced by glycemic index (GI). With a need to control the postexercise energy balance, appetite responses after meals differing in GI are of particular interest.. We assessed the appetite response to low-glycemic index (LGI) and high-glycemic index (HGI) postexercise meals in type 1 diabetes patients. This assessment also offered us the opportunity to evaluate the influence of GI on appetite responses independently of insulinemia, which confounds findings in individuals without diabetes.. Ten physically active men with type 1 diabetes completed 2 trials in a randomized crossover design. After 45 min of treadmill exercise at 70% of the peak oxygen uptake, participants consumed an LGI (GI ∼37) or HGI (GI ∼92) meal with a matched macronutrient composition, negligible fiber content, and standardized insulin-dose administration. The postprandial appetite response was determined for 180 min postmeal. During this time, circulating glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) concentrations and subjective appetite ratings were determined.. The HGI meal produced an ∼60% greater postprandial glucose area under the curve (AUC) than did the LGI meal (P = 0.008). Insulin, glucagon, and GLP-1 did not significantly differ between trials (P > 0.05). The fullness AUC was ∼25% greater after the HGI meal than after the LGI meal (P < 0.001), whereas hunger sensations were ∼9% lower after the HGI meal than after the LGI meal (P = 0.001).. Under conditions of matched insulinemia and fiber, an HGI postexercise meal suppresses feelings of hunger and augments postprandial fullness sensations more so than an otherwise equivalent LGI meal in type 1 diabetes patients.

Topics: Adult; Appetite Regulation; Combined Modality Therapy; Cross-Over Studies; Diabetes Mellitus, Type 1; Diet, Diabetic; Dietary Fiber; Drug Therapy, Combination; Exercise; Glucagon; Glucagon-Like Peptide 1; Glycemic Index; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Jogging; Male; Meals; Postprandial Period

Unlike in western countries, premixed insulin is widely used as the starter insulin in Asian patients instead of basal insulin. The use of basal-bolus therapy as an intensification regimen is not common in Asia despite poor glycaemic control after starting insulin therapy. An alternative insulin intensification regimen with a similar efficacy and safety profile to basal-bolus therapy, but of higher convenience, is urgently needed. The efficacy and safety of insulin lispro mix thrice-daily was compared with basal-bolus therapy in Asian patients with type 2 diabetes who were insufficiently controlled on twice-daily premixed insulin.. This open-label, randomised, active comparator-controlled, parallel-group trial was done at 24 centres in China, Taiwan, and South Korea. Patients with type 2 diabetes who were inadequately controlled on twice-daily premixed insulin were randomly assigned (1:1) to receive either insulin lispro mix (mix 50 before breakfast and lunch plus mix 25 before dinner) or basal-bolus therapy (insulin glargine at bedtime plus prandial insulin lispro thrice-daily) for 24 weeks. Randomisation was done by a computer-generated random sequence and was stratified by country or region and baseline HbA1c. Treatment assignments were masked from the study team assessing outcomes but not from investigators and patients. The primary outcome was change from baseline in HbA1c at week 24 in all randomly assigned patients who received at least one dose of study drug. Analysis was by modified intention to treat, with the per-protocol population used as a supportive analysis. This study is registered with ClinicalTrials.gov, number NCT01175811.. Between Feb 7, 2011, and Nov 7, 2012, 402 patients were enrolled (199 in the premix group, 203 in the basal-bolus group) and 399 were included in the primary analysis (197 in the premix group, 202 in the basal-bolus group). HbA1c change at week 24 was -1.1% for both treatment groups. The least squares mean difference between groups in HbA1c change from baseline was 0% (95% CI -0.1 to 0.2). Insulin lispro mix was non-inferior to basal-bolus therapy based on the prespecified margin of 0.4%. The frequency of adverse events, and the incidences and 30-day rates of nocturnal and overall hypoglycaemia were comparable between groups. No severe hypoglycaemia was reported.. A premixed insulin lispro regimen thrice-daily was non-inferior to basal-bolus therapy in terms of overall glycaemic control and thus could be an option for intensified insulin regimen in Asian patients with type 2 diabetes who are inadequately controlled with twice-daily premixed insulin.

Topics: Acarbose; Aged; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin Glargine; Insulin Lispro; Male; Metformin; Middle Aged; Republic of Korea; Taiwan; Treatment Outcome

To ensure patient safety when replacing insulin glargine (IG) with neutral protamine Hagedorn (NPH) insulin and to determine differences in blood glucose control, frequency of hypoglycemia, insulin dosing, health resource utilization and quality of life between users of IG and NPH insulin.. A single-site, open-label, randomized, 6-month comparative study of 66 patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Randomization was 1:1 to receive IG or NPH insulin. Data regarding blood glucose control, insulin dosage adjustment and recording of hypoglycemia episodes were obtained through telephone calls; office visits were conducted to measure weight, glycated hemoglobin, fasting plasma glucose and blood glucose profile. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to measure patients' satisfaction with their diabetes treatment.. Rates of symptomatic hypoglycemia did not differ significantly between groups: 37.5±2.2 for the IG group and 31.1±2.1 for the NPH group. However, patients treated with NPH insulin had higher frequencies of severe hypoglycemia (6.1±0.9) compared with 2.7±0.6 for the IG group. A significant difference in changes in glycated hemoglobin (A1C) was observed between the groups: the mean ± standard error A1C decreases from baseline were -0.34%±0.11 for the IG group, vs -0.01%±0.10 for the NPH insulin group. The data obtained from the DTSQ showed greater treatment satisfaction in the IG group compared with the NPH insulin group.. Switching from IG to NPH insulin resulted in more than double the rate of severe hypoglycemias and led to decreased metabolic control. Greater treatment satisfaction was observed with IG, compared with NPH insulin, as measured by change from baseline in the DTSQ scores.

Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus; Drug Substitution; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Patient Satisfaction; Risk Factors; Treatment Outcome

To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1 trial.. EDITION 1 was a multicentre, randomized, open-label, two-arm, phase IIIa study. Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100, as previously randomized, once daily for a further 6-month open-label extension phase. Changes in glycated haemoglobin (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic events and body weight were assessed.. Of 807 participants enrolled in the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned to Gla-100 completed 12 months. Glycaemic control was sustained in both groups (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c -0.17 [95% confidence interval (CI) -0.30 to -0.05]%. The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100. Lower percentages of participants had ≥1 confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h; 86 vs 92%; relative risk 0.94 (95% CI 0.89-0.99)] and during the night [54 vs 65%; relative risk 0.84 (95% CI 0.75-0.94)], while the annualized rates of such hypoglycaemic events were similar. No between-treatment differences in adverse events were apparent.. During 12 months of treatment of T2DM requiring basal and meal-time insulin, glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of hypoglycaemic events and overall tolerability did not differ between treatments.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Meals; Middle Aged; Time Factors; Treatment Outcome

This mechanistic trial compared the pharmacodynamics and safety of lixisenatide and liraglutide in combination with optimized insulin glargine with/without metformin in type 2 diabetes (T2D).. This was a multicenter, randomized, open-label, three-arm trial comparing lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg once daily for 8 weeks in combination with insulin glargine after optimized titration. The primary end point was change from baseline to week 8 in incremental area under the postprandial plasma glucose curve for 4 h after a standardized solid breakfast (AUC PPG0030-0430 h). Changes from baseline in gastric emptying, 24-h plasma glucose profile, HbA1c, fasting plasma glucose (FPG), 24-h ambulatory heart rate and blood pressure, amylase and lipase levels, and adverse events (AEs) were also assessed.. In total, 142 patients were randomized and treated. Lixisenatide 20 µg achieved greater reductions of AUC PPG0030-0430 h compared with liraglutide (marginal mean [95% one-sided CI] treatment difference, -6.0 [-7.8] h ⋅ mmol/L [-108.3 (-140.0) h ⋅ mg/dL] vs. liraglutide 1.2 mg and -4.6 [-6.3] h ⋅ mmol/L [-83.0 (-114.2) h ⋅ mg/dL] vs. liraglutide 1.8 mg; P < 0.001 for both), and gastric emptying was delayed to a greater extent than with liraglutide 1.2 and 1.8 mg (P < 0.001 for treatment comparisons). FPG was unchanged in all treatment arms. At week 8, mean ± SD HbA1c was 6.2 ± 0.4% (44 ± 5 mmol/mol), 6.1 ± 0.3% (44 ± 4 mmol/mol), and 6.1 ± 0.3% (44 ± 4 mmol/mol) for lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg, respectively. At week 8, both liraglutide doses increased marginal mean ± SE 24-h heart rate from baseline by 9 ± 1 bpm vs. 3 ± 1 bpm with lixisenatide (P < 0.001). Occurrence of symptomatic hypoglycemia was higher with lixisenatide; gastrointestinal AEs were more common with liraglutide. Lipase levels were significantly increased from baseline with liraglutide 1.2 and 1.8 mg (marginal mean ± SE increase 21 ± 7 IU/L for both; P < 0.05).. Lixisenatide and liraglutide improved glycemic control in optimized insulin glargine-treated T2D albeit with contrasting mechanisms of action and differing safety profiles.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Gastric Emptying; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Liraglutide; Male; Metformin; Middle Aged; Peptides; Postprandial Period; Treatment Outcome

To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) and the reference product (Lantus(®)) insulin glargine (IGlar) in combination with oral antihyperglycaemic medications in patients with type 2 diabetes (T2D).. This phase III, randomized, double-blind, 24-week study enrolled patients with T2D who were insulin-naïve [glycated haemoglobin (HbA1c) ≥7 and ≤11.0%] or previously on IGlar (HbA1c ≤11%) and treated with ≥2 oral antihyperglycaemic medications. Patients were randomized to receive once-daily LY IGlar (n = 376) or IGlar (n = 380) for 24 weeks. The primary efficacy outcome was to test the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar, as measured by change in HbA1c from baseline to 24 weeks.. Both treatment groups had similar and significant (p < 0.001) within-group decreases in mean HbA1c values from baseline. LY IGlar met non-inferiority criteria compared with IGlar for change in HbA1c from baseline [-1.29 vs -1.34%; respectively, least-squares mean difference 0.052% (95% confidence interval -0.070 to 0.175); p > 0.05]. There were no treatment differences (p > 0.05) in fasting plasma glucose, proportion of patients reaching HbA1c <7% or insulin dose at 24 weeks. Adverse events, allergic reactions, weight change, hypoglycaemia and insulin antibodies were similar between treatment groups. Similar findings were observed in patients who were insulin-naïve or previously treated with IGlar at baseline.. Both LY IGlar and IGlar, when used in combination with oral antihyperglycaemic medications, provided effective and similar glucose control with similar safety profiles in patients with T2D.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Insulin Glargine; Male; Middle Aged

To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) and the reference product (Lantus®) insulin glargine (IGlar) in patients with type 1 diabetes (T1D).. This phase III, randomized, open-label, 52-week study enrolled patients with T1D [glycated haemoglobin (HbA1c) ≤11%] being treated with basal (once-daily) and bolus insulin. Patients were randomized to receive once-daily LY IGlar (n = 268) or IGlar (n = 267) in combination with mealtime insulin lispro for 52 weeks. The primary efficacy outcome was to test the non-inferiority (0.4% and then 0.3% margin) of LY IGlar to IGlar as measured by change in HbA1c from baseline to 24 weeks.. Both treatment groups had similar and significant (p < 0.001) within-group decreases in mean HbA1c values from baseline. LY IGlar met the non-inferiority criteria compared with IGlar for change in HbA1c from baseline to 24 weeks [-0.35 vs -0.46%, least-squares mean difference 0.108% (95% confidence interval -0.002 to 0.219), p > 0.05]. There were no significant (p > 0.05) treatment differences in other efficacy measures, including proportion of patients reaching HbA1c <7%, daily mean blood glucose, and insulin dose at 24 and 52 weeks. At 52 weeks, similar findings were observed between LY IGlar and IGlar for safety outcomes, including adverse events, allergic reactions, hypoglycaemia, weight change and insulin antibodies.. Both LY IGlar and IGlar, when used in combination with mealtime insulin lispro, provided effective and similar glucose control and similar safety profiles.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Antibodies; Insulin Glargine; Insulin Lispro; Male; Meals; Middle Aged; Treatment Outcome

We compared the effects of insulin degludec (IDeg; Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin) and insulin glargine (IGlar; A21Gly,B31Arg,B32Arg human insulin) on the day-to-day variability of fasting plasma glucose (FPG) levels in individuals with type 1 diabetes treated with basal-bolus insulin injections.. The effects of basal-bolus insulin therapy for 4 weeks with either IDeg or IGlar as the basal insulin in adult C-peptide-negative outpatients with type 1 diabetes were investigated in an open-label, multicentre, randomised, crossover trial. Randomisation was conducted using a centralised allocation process. The primary endpoints were the SD and CV of FPG during the final week of each treatment period. Secondary endpoints included serum glycoalbumin level, daily dose of insulin, intraday glycaemic variability and frequency of severe hypoglycaemia.. Thirty-six randomised participants (17 in the IDeg/IGlar and 19 in the IGlar/IDeg groups) were recruited, and data for 32 participants who completed the trial were analysed. The mean (7.74 ± 1.76 vs 8.56 ± 2.06 mmol/l; p = 0.04) and SD (2.60 ± 0.97 vs 3.19 ± 1.36 mmol/l; p = 0.03) of FPG were lower during IDeg treatment than during IGlar treatment, whereas the CV did not differ between the two treatments. The dose of IDeg was smaller than that of IGlar (11.0 ± 5.2 vs 11.8 ± 5.6 U/day; p < 0.01), but other secondary endpoints did not differ between the treatments.. IDeg yielded a lower FPG level and smaller day-to-day variability of FPG at a lower daily dose compared with IGlar in participants with type 1 diabetes. IDeg serves as a good option for basal insulin in the treatment of type 1 diabetes.. University Hospital Medical Information Network 000009965.. This research recieved no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Insulin, Regular, Human; Male; Middle Aged; Reproducibility of Results

Insulin therapy in type 1 diabetes still provides suboptimal outcomes. Insulin glargine 300 units/mL (Gla-300), with a flatter pharmacodynamic profile compared with insulin glargine 100 units/mL (Gla-100), is an approach to this problem.. People with type 1 diabetes, using a mealtime and basal insulin regimen, were randomized open-label to Gla-300 or Gla-100 and to morning or evening injection, continuing the mealtime analog, and followed for 6 months.. Participants (n = 549) were a mean age of 47 years and had a mean duration of diabetes of 21 years and BMI of 27.6 kg/m(2). The change in HbA1c (primary end point; baseline 8.1%) was equivalent in the two treatment groups (difference, 0.04% [95% CI -0.10 to 0.19]) (0.4 mmol/mol [-1.1 to 2.1]), and Gla-300 was thus noninferior. Similar results with wider 95% CIs were found for morning and evening injection times and for prebreakfast self-measured plasma glucose (SMPG) overall. Results were also similar for Gla-300 when morning and evening injection time was compared, including overlapping 8-point SMPG profiles. Hypoglycemia did not differ, except for the first 8 weeks of the study, when nocturnal confirmed or severe hypoglycemia was lower with Gla-300 (rate ratio 0.69 [95% CI 0.53-0.91]). Hypoglycemia with Gla-300 did not differ by time of injection. The basal insulin dose was somewhat higher at 6 months for Gla-300. The adverse event profile did not differ and was independent of the Gla-300 time of injection. Weight gain was lower with Gla-300.. In long-duration type 1 diabetes, Gla-300 provides similar glucose control to Gla-100, with a lower risk of hypoglycemia after transfer from other insulins, independent of time of injection, and less weight gain.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Weight Gain

To test the hypothesis that a 'basal plus' regimen--adding once-daily main-meal fast-acting insulin to basal insulin once daily--would be non-inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction.. This open-label trial enrolled adults to an 8- or 12-week run-in period, during which oral therapies except metformin were stopped and insulin glargine dose was titrated. Those with fasting glucose <7 mmol/l but HbA1c >7% (53 mmol/mol) were randomized to insulin glargine/glulisine once daily (n = 170) or insulin aspart/aspart protamine 30/70 twice daily (n = 165) for 24 weeks, with dose titration to glucose targets using standardized algorithms.. For HbA1c, the basal plus regimen was non-inferior to biphasic insulin (least squares mean difference, 0.21%, upper 97.5% confidence limit 0.38%) meeting the predefined non-inferiority margin of 0.4%. Treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version and Insulin Treatment Satisfaction Questionnaire total scores) significantly favoured basal plus. No difference was observed between the basal plus and the biphasic insulin groups in responders (HbA1c <7%, 20.6 vs 27.9%; p = 0.12), weight gain (2.06 vs 2.50 kg; p = 0.2), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life average weighted impact (AWI) score) and generic health status (five-dimension European Quality of Life questionnaire). Overall hypoglycaemia rates were similar between groups (15.3 vs 18.2 events/patient-year; p = 0.22); nocturnal hypoglycaemia was higher with the basal plus regimen (5.7 vs 3.6 events/patient-year; p = 0.02).. In long-standing type 2 diabetes with suboptimal glycaemia despite oral therapies and basal insulin, the basal plus regimen was non-inferior to biphasic insulin for biomedical outcomes, with a similar overall hypoglycaemia rate but more nocturnal events.

Topics: Aged; Australia; Biphasic Insulins; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Intention to Treat Analysis; Male; Middle Aged; Patient Dropouts; Quality of Life; United Kingdom

This study compared the efficacy and safety of once-weekly dulaglutide, a glucagon-like peptide-1 receptor agonist, with daily insulin glargine, both combined with maximally tolerated doses of metformin and glimepiride in patients with type 2 diabetes. The primary objective was noninferiority of dulaglutide 1.5 mg to glargine in the HbA1c change from baseline at 52 weeks.. In this 78-week, open-label study, 810 patients were randomized to dulaglutide 1.5 mg, dulaglutide 0.75 mg, or glargine.. The baseline mean ± SD HbA1c was 8.1 ± 1.0% (65.5 ± 10.8 mmol/mol). The least squares mean ± SE HbA1c change from baseline to the primary end point was -1.08 ± 0.06% (-11.8 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, -0.76 ± 0.06% (-8.3 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, and -0.63 ± 0.06% (-6.9 ± 0.7 mmol/mol) for glargine, with an end point mean ± SD dose of 29 ± 26 units (0.33 ± 0.24 units/kg), and a fasting plasma glucose (mean ± SD) of 118 ± 23 mg/dL from self-monitored plasma glucose. Statistical criteria for superiority were met with dulaglutide 1.5 mg and for noninferiority with dulaglutide 0.75 mg. More patients on dulaglutide 1.5 mg achieved HbA1c targets <7.0% (53 mmol/mol) versus glargine (P < 0.001). Body weight decreased with dulaglutide and increased with glargine. Total hypoglycemia rates were lower with dulaglutide; severe hypoglycemia was minimal. Increases in pancreatic enzymes were observed for dulaglutide. Incidence of nausea (15.4, 7.7, and 1.5%) and diarrhea (10.6, 9.2, and 5.7%) were more common with dulaglutide 1.5 mg and 0.75 mg than with glargine.. Once-weekly dulaglutide 1.5 mg, compared with daily insulin glargine without forced titration, demonstrated greater HbA1c reduction and weight loss, with a higher incidence of gastrointestinal adverse events and a lower risk of hypoglycemia.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Gastrointestinal Diseases; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin Glargine; Male; Metformin; Middle Aged; Recombinant Fusion Proteins; Sulfonylurea Compounds; Treatment Outcome; Weight Loss

To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs).. EDITION 2 (NCT01499095) was a randomized, 6-month, multicentre, open-label, two-arm, phase IIIa study investigating once-daily Gla-300 versus Gla-100, plus OADs (excluding sulphonylureas), with a 6-month safety extension.. Similar numbers of participants in each group completed 12 months of treatment [Gla-300, 315 participants (78%); Gla-100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline -0.55 (0.06)% for Gla-300 and -0.50 (0.06)% for Gla-100; LS mean difference -0.06 [95% confidence interval (CI) -0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla-300 compared with Gla-100: rate ratio 0.63 [(95% CI 0.42-0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71-0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla-300 than Gla-100 [LS mean difference -0.7 (95% CI -1.3 to -0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla-300 and Gla-100 groups).. In people with type 2 diabetes treated with Gla-300 or Gla-100, and non-sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla-300 group.

Topics: Administration, Oral; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Compounding; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Injections, Subcutaneous; Insulin Glargine; Intention to Treat Analysis; Isophane Insulin, Human; Middle Aged; Patient Dropouts; Patient Satisfaction; Risk; Weight Gain

To evaluate 0.75 mg of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, compared with once-daily insulin glargine for glycaemic control in Japanese patients with type 2 diabetes (T2D).. In this phase III, randomized, open-label, parallel-group, 26-week study, 361 patients with inadequately controlled T2D receiving sulphonylureas and/or biguanides, aged ≥20 years, with glycated haemoglobin (HbA1c) levels 7.0-10.0% (53-86 mmol/mol), inclusive, were randomized (1 : 1) to receive dulaglutide or glargine. Participants and investigators were not masked to treatment allocation. The primary measure was change from baseline in HbA1c at 26 weeks, analysed using a mixed-effects model for repeated measures, with a predefined non-inferiority margin of 0.4%.. At week 26, least-squares (LS) mean (standard error) reductions in HbA1c were -1.44 (0.05)% [-15.74 (0.55) mmol/mol] in the dulaglutide group and -0.90 (0.05)% [-9.84 (0.55) mmol/mol] in the glargine group. The mean between-group treatment difference in HbA1c was -0.54% (95% CI -0.67, -0.41) [-5.90 mmol/mol (95% CI -7.32, -4.48)]; p < 0.001. Dulaglutide significantly reduced body weight compared with glargine at week 26 (LS mean difference -1.42 kg, 95% CI -1.89, -0.94; p < 0.001). The most frequent adverse events with dulaglutide treatment were nasopharyngitis and gastrointestinal symptoms. The incidence of hypoglycaemia was significantly lower with dulaglutide [47/181 (26%)] compared with glargine [86/180 (48%)], p < 0.001.. In Japanese patients with T2D uncontrolled on sulphonylureas and/or biguanides, once-weekly dulaglutide was superior to once-daily glargine for reduction in HbA1c at 26 weeks. Although dulaglutide increased gastrointestinal symptoms, it was well tolerated, with an acceptable safety profile.

Topics: Aged; Biguanides; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin Glargine; Japan; Male; Middle Aged; Nasopharyngitis; Recombinant Fusion Proteins; Sulfonylurea Compounds

Premixed insulin is a commonly prescribed formulation for the outpatient management of patients with type 2 diabetes. The safety and efficacy of premixed insulin formulations in the hospital setting is not known.. In a prospective, open-label trial, we randomized general medicine and surgery patients to receive a basal-bolus regimen with glargine once daily and glulisine before meals (n = 33) or premixed human insulin (30% regular insulin and 70% NPH insulin) twice daily (n = 39). Major outcomes included differences in daily blood glucose (BG) levels and frequency of hypoglycemic events (<70 mg/dL) between treatment groups.. At the first prespecified interim analysis, the study was stopped early because of an increased frequency of hypoglycemia >50% in patients treated with premixed human insulin. A total of 64% of patients treated with premixed insulin experienced one or more episodes of hypoglycemia compared with 24% in the basal-bolus group (P < 0.001). There were no differences in mean daily BG level after the first day of insulin treatment (175 ± 32 vs. 179 ± 43 mg/dL, P = 0.64) between groups. A BG target between 80 and 180 mg/dL before meals was achieved in 55.9% of BG readings in the basal-bolus group and 54.3% of BG readings in the premixed insulin group (P = 0.23). There was no difference in the length of hospital stay or mortality between treatment groups.. Inpatient treatment with premixed human insulin resulted in similar glycemic control but in significantly higher frequency of hypoglycemia compared with treatment with basal-bolus insulin regimen in hospitalized patients with diabetes.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged; Prospective Studies

To investigate the clinical efficacy and safety of insulin glargine compared with NPH insulin as basal insulin for the management of corticosteroid-induced hyperglycemia in hospitalized people with type 2 diabetes (T2DM) and respiratory disease.. Randomized, two-arm parallel group, clinical trial undertaken from February 2011 to November 2012 on the pneumology ward of the Hospital Regional Universitario de Málaga (Spain), involving 53 participants with T2DM treated with medium/high doses of intermediate-acting corticosteroids. Participants were randomly assigned to receive one single dose of insulin glargine or NPH insulin in three equally divided doses before each meal as basal insulin within a basal-bolus insulin protocol. The intervention lasted six days or until discharge if earlier.. No significant differences were seen between groups during the study in mean blood glucose (11.43±3.44 mmol/l in glargine vs. 11.88±2.94 mmol/l in NPH, p=0.624), and measures of glucose variability (standard deviation 3.27±1.16 mmol/l vs. 3.61±0.99 mmol/l, p=0.273; coefficient of variation 1.55±0.33 mmol/l vs. 1.72±0.39 mmol/l, p=0.200). Results from CGM were concordant with those obtained with capillary blood glucose reading. The length of hospital stay was also similar between groups (8.2±2.8 days vs. 9.8±3.4 days, p=0.166) There was a non significant trend for lower episodes of mild (4 vs. 8, p=0.351) and severe hypoglycemia (0 vs. 3, p=0.13) in the glargine group.. The results of this study showed that insulin glargine and NPH insulin are equally effective in a basal-bolus insulin protocol to treat glucocorticoid-induced hyperglycemia in people with T2DM on a pneumology ward.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Respiratory Tract Diseases; Safety; Young Adult

Insulin degludec (Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin; IDeg) is a new basal insulin with an ultra-long flat action profile. The acute physiological responses to hypoglycaemia with IDeg and insulin glargine (A21Gly,B31Arg,B32Arg human insulin; IGlar) were compared.. Twenty-eight adult type 1 diabetic patients with normal hypoglycaemia awareness (age = 41 ± 12 years, HbA1c = 7.8 ± 0.6% [62.8 ± 7 mmol/mol]) were randomised to once-daily IDeg or IGlar for 5 days in a two-period crossover design. Participants and research staff were blinded to group assignment. Patients were assigned the lowest available randomisation number from a set of blinded randomisation codes provided by the trial sponsor. Hypoglycaemia was induced by administering three times the usual daily insulin dose at midnight on day 5. Plasma glucose (PG) was stabilised by glucose clamp (5.5 mmol/l) for 7-9 h post dosing. Next morning, PG was allowed to decrease stepwise from 5.5 to 3.5 mmol/l (maintained for 30 min) to 2.5 mmol/l (for 15 min). PG was then increased to 3.9 mmol/l (for 120 min), before being returned to baseline. Hypoglycaemic symptom score (HSS), hypoglycaemic awareness, cognitive function, counter-regulatory hormones and vital signs were assessed during each glucose plateau. The primary analysis was to compare IDeg vs IGlar with respect to HSS at nadir PG concentration (2.5 mmol/l).. The full analysis set for treatment comparisons comprised data from all 28 exposed patients. Rates of PG decline and PG at nadir were similar for IDeg and IGlar. No treatment differences in HSS (estimated difference: 0.17 [95% CI -1.71, 2.05]; p > 0.05), cognitive function or awareness were observed at any time. Growth hormone and cortisol responses during hypoglycaemia were greater with IDeg than IGlar (AUC treatment ratio [IDeg/IGlar]: 2.44 [1.30, 4.60], p < 0.01; and 1.23 [1.01, 1.50]; p < 0.05), and adrenaline (epinephrine) responses trended higher (1.40 [0.96, 2.04], p = 0.07). The rates of recovery from hypoglycaemia were similar.. IDeg and IGlar elicit comparable symptomatic and cognitive responses to induced hypoglycaemia. IDeg may elicit a moderately greater endocrine response, but times to PG recovery were similar for the two insulins.. ClinicalTrials.gov NCT01002768.. Novo Nordisk.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Hypoglycemia; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

Few studies have evaluated long-term durability of glycemic control in older patients. The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25; 75 % insulin lispro protamine suspension, 25 % insulin lispro) and once-daily insulin glargine (GL) added to oral antihyperglycemic medications in older patients (≥65 years of age).. Patients were participants in the maintenance phase of the DURABLE trial. During the initiation phase, patients with type 2 diabetes were randomized to LM75/25 or GL. After 6 months, patients with hemoglobin A1c (HbA1c) ≤7.0 % advanced to the 24-month maintenance phase. The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients (≥65 years of age). A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase.. Median time of maintaining HbA1c goal was longer in LM75/25 versus GL (19.6 versus 15.4 months, p = 0.007) and more LM75/25 patients maintained goal versus GL (49.2 versus 30.4 %; p = 0.003). HbA1c reduction from baseline was greater in LM75/25 versus GL (-1.56 ± 0.10 versus -1.24 ± 0.11 %; p = 0.003). Post-meal glucose was significantly lower in LM75/25 versus GL (158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL; p = 0.017). No differences were observed in overall and severe hypoglycemia. LM75/25 patients had higher daily insulin doses (0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day; p < 0.001) and more weight gain (5.47 ± 0.49 versus 3.10 ± 0.53 kg; p = 0.001). Similar results were generally obtained in older patients with HbA1c ≤6.5 %.. In our evaluation of older patients from a larger trial, LM75/25 appeared to provide longer durability of glycemic control, as well as a greater number of patients maintaining HbA1c goal versus GL.

Topics: Aged; Aging; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Maintenance Chemotherapy; Male

OBJECTIVE Diabetes self-management is universally regarded as a foundation of diabetes care. We determined whether comparable glycemic control could be achieved by self-titration versus physician titration of a once-daily bolus insulin dose in patients with type 2 diabetes who are unable to achieve optimal glycemia control with a basal insulin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes, an HbA1c level >7% (53 mmol/mol), and either nocturnal hypoglycemia episodes or an insufficient basal insulin glargine level (with or without oral agents) to achieve a fasting plasma glucose level ≤6 mmol/L (108 mg/dL) were studied. Participants all had bolus insulin glulisine added at breakfast and were allocated to either algorithm-guided patient self-titration or physician titration. The primary outcome was an HbA1c level ≤7% (53 mmol/mol) without severe hypoglycemia. RESULTS After a mean (SD) follow-up of 159.4 days (36.2 days), 28.4% of participants in the self-titration arm vs. 21.2% in the physician titration arm achieved an HbA1c level of ≤7% (53 mmol/mol) without severe hypoglycemia (between-group absolute difference 7.2%; 95% CI -3.2 to 17.7). The lower end of this 95% confidence interval was within the predetermined noninferiority boundary of -5% (P noninferiority = 0.011). CONCLUSIONS In stable patients with type 2 diabetes who are receiving doses of basal insulin glargine who require bolus insulin, a simple bolus insulin patient-managed titration algorithm is as effective as a physician-managed algorithm.

Topics: Adult; Aged; Algorithms; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Self Administration; Treatment Outcome

To use continuous glucose monitoring (CGM) to evaluate the impact of the novel, long-acting basal insulin analog LY2605541 on hypoglycemia and glycemic variability in patients with type 2 diabetes.. Hypoglycemia and glucose variability were assessed with CGM of interstitial glucose (IG) in a subset of patients with type 2 diabetes from a phase II, randomized, open-label, parallel study of LY2605541 (n = 51) or insulin glargine (GL) (n = 25). CGM was conducted on 3 consecutive days (72-84 h) during the week before week 0, 6, and 12 study visits.. Measured by CGM for 3 days prior to the 12-week visit, fewer LY2605541-treated patients experienced hypoglycemic events overall (50.0 vs. 78.3%, P = 0.036) and nocturnally (20.5 vs. 47.8%, P = 0.027) and spent less time with IG ≤70 mg/dL than GL-treated patients during the 24-h (25 ± 6 vs. 83 ± 16 min, P = 0.012) and nocturnal periods (11 ± 5 vs. 38 ± 13 min, P = 0.024). These observations were detected without associated differences in the average duration of individual hypoglycemic episodes (LY2605541 compared with GL 57.2 ± 5.4 vs. 69.9 ± 10.2 min per episode, P = NS). Additionally, LY2605541-treated patients had lower within-day glucose SD for both 24-h and nocturnal periods.. By CGM, LY2605541 treatment compared with GL resulted in fewer patients with hypoglycemic events and less time in the hypoglycemic range and was not associated with protracted hypoglycemia.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Polyethylene Glycols; Treatment Outcome

To compare efficacy and safety of two, once-daily basal insulin formulations [insulin lispro protamine suspension (ILPS) vs. insulin glargine (glargine)] added to oral antihyperglycaemic medications (OAMs) and exenatide BID in suboptimally controlled type 2 diabetes (T2D) patients.. This 24-week, open-label, multicentre trial randomized patients to bedtime ILPS (n = 171) or glargine (n = 168). Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of 95% confidence intervals (CIs) for change in haemoglobin A1c (HbA1c) from baseline to week 24 (adjusted for baseline HbA1c) with non-inferiority margin 0.4%.. Non-inferiority of ILPS versus glargine was demonstrated: least-squares mean between-treatment difference (ILPS minus glargine) (95% CI) was 0.22% (0.06, 0.38). Mean HbA1c reduction was less for ILPS- versus glargine-treated patients (-1.16 ± 0.84 vs. -1.40 ± 0.97%, p = 0.008). Endpoint HbA1c < 7.0% was achieved by 53.7% (ILPS) and 61.7% (glargine) (p = NS). Overall hypoglycaemia rates (p = NS) and severe hypoglycaemia incidence (p = NS) were similar. Nocturnal hypoglycaemia rate was higher in patients treated with ILPS versus glargine (p = 0.004). Weight gain was similar between groups (ILPS: 0.27 ± 3.38 kg; glargine: 0.66 ± 3.93 kg, p = NS). Endpoint total insulin doses were lower in patients treated with ILPS versus glargine (0.30 ± 0.17 vs. 0.37 ± 0.17 IU/kg/day, p < 0.001).. ILPS was non-inferior to glargine for HbA1c change over 24 weeks, but was associated with less HbA1c reduction and more nocturnal hypoglycaemia. Treat-to-target basal insulin therapy improves glycaemic control and is associated with minimal weight gain when added to OAMs and exenatide BID for suboptimally controlled T2D.

Topics: Administration, Oral; Adolescent; Adult; Aged; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Protamines; Treatment Outcome; Weight Gain; Young Adult

The primary objective of this prospective controlled study was to investigate the impact of standardized injection-site warming on prandial rapid acting insulin dose and glycemic control when studied under real-world conditions.. All 145 participating patients (51 female, 94 male, 13 type 1 and 132 type 2 patients, age: 61.6 ± 8.4 yrs, HbA1c: 7.19 ± 0.50%) were treated with intensive insulin glargine and short-acting insulin analog therapy. After a 4 week treatment optimization run-in period, patients were randomized to continue therapy for three months without (control) or with a local injection-site warming device (InsuPad * ). Observation parameters included HbA1c, insulin dose, frequency of hypoglycemia, body weight and adverse events.. HbA1c improved in both arms until study end (control group: 6.3 ± 0.5%; injection-site warming device: 6.3 ± 0.5%; both p < 0.001 vs. baseline). To achieve this good control, patients in the control group needed to increase the daily prandial insulin dose by 8.1% (from 66 ± 31 U to 71 ± 38 U, p < 0.05) with stable basal insulin requirements. Patients who used the injection-site warming device required less prandial insulin (70 ± 43 U to 55 ± 34 U; -19%, p < 0.001) and slightly more basal insulin (+3.9%). Total daily insulin dose increased in the control group (+3.7%) and decreased with warming device use (-8.6%, p < 0.001). The number of hypoglycemic events (<63 mg/dL) during the observation period was higher in the control group (6.2 ± 9.9/patient vs. injection-site warming device: 3.3 ± 4.8/patient, p < 0.05). Main study limitations can be seen in the open label design reliability of the collected dose information and the very obese patient cohort.. When treating obese patients to target with insulin therapy, use of an injection-site warming device for 3 months resulted in a lower frequency of hypoglycemic events and a reduction in prandial insulin analog requirements. If these results are confirmed in other patient populations, an injection-site warming device may be useful in achieving treatment targets with a safer and more efficient basal bolus therapy in insulin-treated patients with type 1 and type 2 diabetes.

Topics: Absorption; Animals; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hyperthermia, Induced; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity; Postprandial Period; Prospective Studies

The aim of present study is to assess whether if basal insulin, glargine, could improve insulin secretory function of β-cells compared with glimepiride when metformin alone was failed. This was an open-label and multi-center study for 52 weeks in Korean patients with uncontrolled type 2 diabetes by metformin monotherapy. Subjects were randomized to glargine or glimepiride groups (n = 38 vs. 36, respectively). The primary endpoint was to compare changes in c-peptide via glucagon test after 48 weeks. Glycemic efficacy and safety endpoints (glycated hemoglobin (HbA1c), HOMA-B, fasting plasma glucose (FPG), lipid profiles, and hypoglycemic events) were also checked. The mean disease duration of all subjects was 88.2 months. Changes in C-peptide was no significant different between groups (P = 0.73), even though insulin secretion was not worsened in both groups at the endpoint. Glargine was not superior to glimepiride in other β-cell function indexes such as HOMA-B (P = 0.28). HbA1c and FPG reduced significantly in each groups but not different between two groups. Although, severe hypoglycemia did not occur, symptomatic hypoglycemia was more frequent in glimepiride group (P = 0.01). Insulin glargine was as effective as glimepiride in controlling hyperglycemia and maintaining β-cell function in Korean patients with type 2 diabetes during 48 weeks study period, after failure of metformin monotherapy. Hypoglycemic profile was favorable in the insulin glargine group and less weight gain was observed in the glimepiride group. Our results suggest that glargine and glimepiride can be considered after failure of metformin monotherapy.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Chi-Square Distribution; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Republic of Korea; Sulfonylurea Compounds; Young Adult

Insulin degludec (IDeg) is a new basal insulin with an ultra-long and stable glucose-lowering effect. We compared once-daily IDeg and insulin glargine (IGlar), both in combination with metformin ± dipeptidyl peptidase-4 inhibitors, in a 52-week, open-label, treat-to-target trial in patients with type 2 diabetes followed by a 52-week extension trial in which subjects [n = 725/1030 (70.4%)] maintained their initial randomised treatment. Health status was assessed at baseline and 105 weeks using the Short Form-36 (SF-36 v2) questionnaire. SF-36 scores were analysed (ITT population) using anova, with adjustments for covariates. At 105 weeks, the overall physical component score was significantly better with IDeg versus IGlar [treatment contrast (TC): 1.1 (0.1; 2.1)95% CI , p < 0.05]. This was largely because of significantly better physical functioning [TC: 1.1 (0.0; 2.3)95% CI , p < 0.05] and bodily pain sub-domain scores [TC: 1.5 (0.2; 2.9)95% CI , p < 0.05]. Improvements in health status with IDeg compared to IGlar were maintained after 2 years.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Drug Therapy, Combination; Health Status; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Metformin; Treatment Outcome

To compare the commonly prescribed oral anti-diabetic drug (OAD) combinations to use as an add-on therapy with insulin glargine in patients with uncontrolled type 2 diabetes despite submaximal doses of OADs.. People with inadequately controlled type 2 diabetes (n = 99) were randomly assigned on a 1∶1∶1 basis to receive insulin glargin, with fixed doses of glimepiride, metformin, and glimepiride plus metformin. Outcomes assessed included HbA1c, the changes in fasting glucose levels, body weight, serum lipids values, insulin dose and symptomatic hypoglycemia.. After 24 weeks, HbA1C levels improved from (mean ± SD) 8.5±0.9% to 7.7±0.8% (69.0±10.0 mmol/mol to 60.8±8.6 mmol/mol) with insulin glargine plus metformin, from 8.4±1.0% to 7.7±1.3% (68.8±10.6 mmol/mol to 61.1±14.4 mmol/mol) with insulin glargine plus glimepiride and from 8.7±0.9% to 7.3±0.6% (71.7±9.8 mmol/mol to 56.2±6.7 mmol/mol) with insulin glargine plus glimepirde plus metformin. The decrease in HbA1c was more pronounced with insulin glargine plus glimepiride plus metformin than with insulin glargine plus metformin (0.49% [CI, 0.16% to 0.82%]; P = 0.005) (5.10 mmol/mol [CI, 1.64 to 8.61]; P = 0.005) and insulin glargine plus glimepiride (0.59% [CI, 0.13% to 1.05%]; P = 0.012) (5.87 mmol/mol [CI, 1.10 to 10.64]; P = 0.012) (overall P = 0.02). Weight gain and the risk of hypoglycemia of any type did not significantly differ among the treatment groups.. The combination therapy of metformin and glimepiride plus glargine insulin resulted in a significant improvement in overall glycemic control as compared with the other combinations.. ClinicalTrials.gov, NCT00708578. The approval number of Kangbuk Samsung hospital's institutional review board (IRB): C0825.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Glargine; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Young Adult

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established.. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire.. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores.. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients.

Topics: Adult; Aged; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Patient Satisfaction

The basal insulin analogue LY2605541, a PEGylated insulin lispro with prolonged duration of action, was previously shown to be associated with modest weight loss in Phase 2, randomized, open-label trials in type 2 (N=288) and type 1 (N=137) diabetes mellitus (T2DM and T1DM), compared with modest weight gain with insulin glargine. Exploratory analyses were conducted to further characterize these findings.. Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements. Proportions of subjects with weight loss were analysed using Fisher's exact test for T2DM and Nagelkerke's method for T1DM.. Weight loss was more common in LY2605541-treated patients than in patients treated with insulin glargine (T2DM: 56.9 vs. 40.2%, p=0.011; T1DM: 66.1 vs. 40.3%, p<0.001). More LY2605541-treated patients experienced ≥5% weight loss compared to patients treated with glargine (T2DM: 4.8 vs. 0%, p=0.033; T1DM: 11.9 vs. 0.8%, p<0.001). In both the T1DM and T2DM studies, weight change did not correlate with baseline body mass index (BMI), or change in HDL-cholesterol in either treatment group. No consistent correlations were found across both studies between weight change and any of the variables assessed; however, weight change was significantly correlated with hypoglycaemia rate in glargine-treated T2DM patients.. In two Phase 2 trials, improved glycaemic control with long-acting basal insulin analogue LY2605541 is associated with weight loss in previously insulin-treated patients. This weight change is independent of baseline BMI or hypoglycaemia.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Polyethylene Glycols; Treatment Outcome; Weight Gain; Weight Loss

To compare the efficacy and safety of two insulin intensification strategies in patients with type 2 diabetes inadequately controlled on basal insulin glargine with metformin and/or pioglitazone.. A multinational, randomized, open-label trial that compared insulin lispro low mixture (LM25; n = 236) twice daily with a basal-prandial regimen of insulin glargine once daily and insulin lispro once daily (IGL; n = 240) over 24 weeks in patients with HbA1c 7.5-10.5% and fasting plasma glucose ≤ 6.7 mmol/l. The primary objective was to assess non-inferiority [per-protocol (PP) population], and then superiority [intention-to-treat (ITT) population], of LM25 versus IGL according to change in HbA1c after 24 weeks (non-inferiority margin 0.4%, two-sided significance level 0.05).. Estimated change [least squares (LS) mean (95% CI)] in HbA1c after 24 weeks: -1.30 (-1.44, -1.16)% with LM25 and -1.08 (-1.22, -0.94)% with IGL. Non-inferiority was shown [LS mean (95% CI) HbA1c treatment difference -0.21 (-0.38, -0.04) (PP population)]; gated superiority assessment showed a statistically significant advantage for LM25 (p = 0.010; ITT population). Mean blood glucose, glycaemic variability, overall tolerability and hypoglycaemic episodes per patient-year did not show significant differences between treatments during the study.. In patients with type 2 diabetes inadequately controlled on once-daily basal insulin glargine and metformin and/or pioglitazone, intensification with LM25 was superior to a basal-prandial approach in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycaemia episodes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Meals; Metformin; Middle Aged; Pioglitazone; Thiazolidinediones; Treatment Outcome

To compare two self-titration algorithms for initiating and escalating prandial insulin lispro in patients with type 2 diabetes inadequately controlled on basal insulin.. The trial was designed as two independent, multinational, parallel, open-label studies (A and B), identical in design, to provide substantial evidence of efficacy and safety in endocrine and generalist settings. Subjects were 18-85 years old (study A: N = 528; study B: N = 578), on basal insulin plus oral antidiabetic drugs for ≥3 months, and had an HbA1c 7.0% to ≤12.0% (>53.0 to ≤107.7 mmol/mol). Once optimized on insulin glargine, subjects were randomized to one of two self-titration algorithm groups adjusting lispro either every day (Q1D) or every 3 days (Q3D) for 24 weeks. The primary outcome was the change in HbA1c from baseline. The primary and secondary objectives were evaluated for the overall population and subjects ≥65 years old.. Baseline HbA1c was similar (study A: Q1D 8.3% [67.2 mmol/mol] vs. Q3D 8.4% [68.3 mmol/mol], P = 0.453; study B: Q1D 8.3% [67.2 mmol/mol] vs. Q3D 8.4% [68.3 mmol/mol], P = 0.162). Both algorithms had significant and equivalent reductions in HbA1c from baseline (study A: Q3D -0.96% [-10.49 mmol/mol], Q1D -1.00% [-10.93 mmol/mol], Q3D-Q1D 0.04% [0.44 mmol/mol] [95% CI -0.15 to 0.22 (-1.64 to 2.40)]; study B: Q3D -0.92% [-10.06 mmol/mol], Q1D -0.98% [-10.71 mmol/mol], Q3D-Q1D 0.06% [0.66 mmol/mol] [95% CI -0.12 to 0.24 (-1.31 to 2.62)]). The incidence and rate of hypoglycemia were similar for Q3D and Q1D in both studies. In general, no clinically relevant differences were found between the two algorithms in subjects ≥65 years old in either study.. Prandial insulin lispro can effectively and safely be initiated, by either of two self-titrated algorithms, in a variety of practice settings.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

Because insulin dosing requires optimization of glycemic control, it is important to use a single metric of benefit and risk to determine best insulin dosing practices. We retrospectively applied a multiplicative clinical utility index (CUI) to a study of LY2605541 (Eli Lilly and Company, Indianapolis, IN), a novel, long-acting basal insulin.. A CUI was developed to transform the multidimensional problem of assessing benefit/risk of multiple dosing algorithms into a single decision-making metric to evaluate two LY2605541 dosing algorithms relative to the insulin glargine (GL) dosing algorithm. The CUI was applied to data in a 12-week, open-label, Phase 2 trial in patients with type 2 diabetes mellitus who were randomized to one of two dosing algorithms for LY2605541 (LY1 or LY2) or GL (algorithm similar to LY1). The CUI was created (via expert input) by weighing the relative benefit/risk of four components (glycosylated hemoglobin [HbA1c], percentage of patients with HbA1c ≤ 7%, hypoglycemia rate, and time to steady-state dose); individual utility values were multiplied to compute CUI values for LY1 and LY2 relative to GL, and bootstrap samples were used to determine variability.. The mean CUI was 0.82 for LY1 and 1.35 for LY2. Based on 3,000 bootstrap samples, there was a 48% probability of LY2 performing better than LY1 and a 28% probability of LY1 performing better than LY2.. CUI methodology, and in particular this CUI, is a useful tool for comparing dosing algorithms. Based on this CUI, LY2 is likely to be a better dosing algorithm than LY1.

Topics: Algorithms; Blood Glucose; Clinical Trials, Phase II as Topic; Decision Making; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Polyethylene Glycols; Retrospective Studies; Risk Assessment; Treatment Outcome

The authors present and analyze the outcome of DIABOBHU observational study. The work was carried out in Hungarian type 2 diabetic patients whose treatment was insufficient with oral antidiabetic agents.. The safety and efficacy of glargine insulin added to oral antidiabetic therapy treatment was evaluated.. Between 2008 and 2011 3955 patients were enrolled. After proper education, patients titrated the insulin dosage under self-monitoring with the help of their attending physicians. During the 26-week study period 3 visits were included. The primary endpoint was the change of HbA1c. The secondary endpoints were fasting glucose levels, dose of insulin, body weight and body mass index, satisfaction of the patients with the treatment and the incidence of hypoglycemic events.. During the study mean HbA1c decreased from 8.94% to 7.31%. Most patients achieved the glycemic goals with very low frequency of hypoglycemia. The patients did not gain weight and were satisfied with their treatment.. The authors emphasize that this treatment based on an analogue basal insulin should be considered as an effective and safe therapy.. Bevezetés: A szerzők ismertetik és elemzik a 2-es típusú, orális antidiabetikumokkal sikertelenül kezelt betegekkel lefolytatott DIABOBHU hazai obszervációs vizsgálat eredményeit. Célkitűzés: A vizsgálat során a diabetológiai gyakorlatban elindított glargin bázisinzulinnal kombinált orális kezelés eredményességét és biztonságosságát értékelték. Módszer: 2008–2011 között összesen 3955 beteg került bevonásra. Oktatást követően a betegek vércukor-önellenőrzés mellett titrálták fel inzulindózisukat a kezelőorvosuk segítségével. A 26 hetes vizsgálati periódusban 3 vizitre került sor. Elsődleges végpontként a HbA1c-szint változása szerepelt négy korcsoportban. Másodlagos végpontként az éhgyomri vércukorértékek, az inzulin dózisa, a testsúly, testtömegindex változása, a kezeléssel kapcsolatos megelégedettség, a hypoglykaemiák incidenciája szerepelt. Eredmények: A kiindulási átlagos 8,94%-os HbA1c 7,31%-ra csökkent. A betegek többsége elérte a glykaemiás célokat igen alacsony hypoglykaemiaráta mellett. A vizsgálat eredményei közül kiemelendő, hogy a betegek testsúlya nem nőtt és kezelésükkel elégedettek voltak. Következtetések: A szerzők hangsúlyozzák, hogy az analóg bázisinzulinnal kombinált orális kezelés ma is hatékony és biztonságos terápiának számít. Orv. Hetil., 2014, 155(23), 903–910.

Topics: Administration, Oral; Adult; Aged; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hungary; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

To assess the effect of initiating insulin treatment on quality of life of patients with type 2 diabetes (T2DM) in the 60-week All-to-Target trial (NCT00384085).. Patient-reported outcomes from a phase IV, multicentre, randomised, open-label, parallel-group study were analysed. Participants were randomised to: insulin glargine with up to one insulin glulisine injection (G + 1); insulin glargine with stepwise addition of up to three insulin glulisine injections (G + 3); or twice-daily premixed 70/30 insulin protamine-aspart/aspart (PM-2). Patient-reported outcome questionnaires were administered at weeks 0, 6, 12, 24, 36, 48 and 60.. There were no between-group differences in the Psychosocial Adjustment to Illness State-Self Report (PAIS-SR) or in the EuroQoL Group Five-Dimension Self-Report Index Questionnaire (EQ-5D) from baseline to week 60; however, PAIS-SR scores improved significantly over this period in the G + 3 group (p = 0.0016) and EQ-5D scores worsened significantly in the PM-2 group (p = 0.02). Hypoglycemia Fear Survey Behaviour and Worry subscales worsened significantly for all groups, with greater deterioration being observed in the PM-2 group than in the G + 1 group (Behaviour, p = 0.0050; Worry, p = 0.0017) and G + 3 groups (Behaviour, p = 0.0105; Worry, p = 0.0016). Total scores on the Diabetes Quality of Life (DQoL) questionnaire improved more in the G + 3 group than in the PM-2 group over the study period (p = 0.0284), with all groups showing a significant improvement in DQoL score over time.. Insulin glargine-based regimens showed advantages over premixed insulin in a number of patient-reported outcome measures. The potential impact on fear of hypoglycaemia may be of particular relevance when addressing the major barriers to early insulin treatment.

Topics: Adult; Aged; Aged, 80 and over; Anxiety; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Outcome Assessment; Quality of Life; Surveys and Questionnaires; United States

Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration.. In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day).. Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (-1.13 and -1.10%, respectively); treatment differences were -0.04 (95% CI -0.18, 0.11) in per-protocol (n = 510) and -0.03 (95% CI -0.16, 0.11) in intent-to-treat (n = 627) populations. FG was lower with exenatide than lispro (6.5 vs. 7.2 mmol/L; P = 0.002). Weight decreased with exenatide and increased with lispro (-2.5 vs. +2.1 kg; P < 0.001). More patients reported treatment satisfaction and better quality of life with exenatide than lispro, although a larger proportion of patients with exenatide experienced treatment-emergent adverse events. Exenatide resulted in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro.. Adding exenatide to titrated glargine with metformin resulted in similar glycemic control as adding lispro and was well tolerated. These findings support exenatide as a noninsulin addition for patients failing basal insulin.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Meals; Metformin; Middle Aged; Peptides; Quality of Life; Receptors, Glucagon; Treatment Outcome; Venoms

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens.. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups.. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence of hypoglycemia was 4.1%, 2.0%, and 6.3%, respectively (P = 0.557).. The currently proposed weight-based insulin glargine dose titration regimen is effective, tolerable, and user-friendly at achieving FBG target levels in hospitalized patients with hyperglycemia.

Topics: Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Middle Aged; Research Design

To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin.. EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallel-group study. Adults with glycated hemoglobin A1c (HbA1c) 7.0-10.0% (53-86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L. Primary end point was HbA1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6.. Participants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m(2), and HbA1c 8.15% (65.6 mmol/mol). HbA1c reduction was equivalent between regimens; least squares mean difference -0.00% (95% CI -0.11 to 0.11) (-0.00 mmol/mol [-1.2 to 1.2]). Fewer participants reported one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67-0.93]; P < 0.005); nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified.. Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Meals; Middle Aged

Effective treatment algorithms are needed to guide diabetes care at hospital discharge in general medicine and surgery patients with type 2 diabetes.. This was a prospective, multicenter open-label study aimed to determine the safety and efficacy of a hospital discharge algorithm based on admission HbA1c. Patients with HbA1c <7% (53.0 mmol/mol) were discharged on their preadmission diabetes therapy, HbA1c between 7 and 9% (53.0-74.9 mmol/mol) were discharged on a preadmission regimen plus glargine at 50% of hospital daily dose, and HbA1c >9% were discharged on oral antidiabetes agents (OADs) plus glargine or basal bolus regimen at 80% of inpatient dose. The primary outcome was HbA1c concentration at 12 weeks after hospital discharge.. A total of 224 patients were discharged on OAD (36%), combination of OAD and glargine (27%), basal bolus (24%), glargine alone (9%), and diet (4%). The admission HbA1c was 8.7 ± 2.5% (71.6 mmol/mol) and decreased to 7.3 ± 1.5% (56 mmol/mol) at 12 weeks of follow-up (P < 0.001). The change of HbA1c from baseline at 12 weeks after discharge was -0.1 ± 0.6, -0.8 ± 1.0, and -3.2 ± 2.4 in patients with HbA1c <7%, 7-9%, and >9%, respectively (P < 0.001). Hypoglycemia (<70 mg/dL) was reported in 22% of patients discharged on OAD only, 30% on OAD plus glargine, 44% on basal bolus, and 25% on glargine alone and was similar in patients with admission HbA1c ≤7% (26%) compared with those with HbA1c >7% (31%, P = 0.54).. Measurement of HbA1c on admission is beneficial in tailoring treatment regimens at discharge in general medicine and surgery patients with type 2 diabetes.

Topics: Adult; Aged; Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Discharge; Prospective Studies; Treatment Outcome

To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes using basal insulin (≥42 units/day) plus oral antihyperglycemic drugs (OADs).. EDITION 2 was a multicenter, open-label, two-arm study. Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point was change in HbA1c. The main secondary end point was percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemic events from week 9 to month 6.. Randomized participants (n = 811) had a mean (SD) HbA₁c of 8.24% (0.82) and BMI of 34.8 kg/m(2) (6.4). Glycemic control improved similarly with both basal insulins; least squares mean (SD) reduction from baseline was -0.57% (0.09) for Gla-300 and -0.56% (0.09) for Gla-100 (mean difference -0.01% [95% CI -0.14 to 0.12]), with 10% higher dose of Gla-300. Less nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 (relative risk 0.77 [95% CI 0.61-0.99]; P = 0.038) and during the first 8 weeks. Fewer nocturnal and any time (24 h) hypoglycemic events were reported during the entire 6-month period. Weight gain was lower with Gla-300 than with Gla-100 (P = 0.015). No between-treatment differences in safety parameters were identified.. Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

To evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator - Registered Nurse (CDE-RN) support.. Insulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation.. Ninety-two patients mean age (range) 59 (28-77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p=0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002).. Insulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition. Trial registration ACTRN12610000797077.

Topics: Adult; Aged; Australia; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Acceptance of Health Care; Postprandial Period; Primary Health Care; Retrospective Studies

This study assessed the efficacy and safety of once-daily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 diabetes (T2D).. This 26-week, multinational, randomized, treat-to-target trial involved 457 insulin-naïve adults with T2D (HbA1c 7-9%). Detemir or glargine was added to current metformin therapy [any second oral antidiabetic drug (OAD) discontinued] and titrated to a target fasting plasma glucose (FPG) ≤90 mg/dl (≤5.0 mmol/l). Primary efficacy endpoint was change in HbA1c.. Mean (s.d.) HbA1c decreased with detemir and glargine by 0.48 and 0.74%-points, respectively, to 7.48% (0.91%) and 7.13% (0.72%) [estimated between-treatment difference, 0.30 (95% CI: 0.14-0.46)]. Non-inferiority for detemir at the a priori level of 0.4%-points was not established. The proportions of patients reaching HbA1c ≤ 7% at 26 weeks were 38% and 53% (p = 0.026) with detemir and glargine, respectively. FPG decreased ∼43.2 mg/dl (∼2.4 mmol/l) in both groups [non-significant (NS)]. Treatment satisfaction was good for both insulins. Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine [rate ratio 0.73 (95% CI 0.54-0.98)]. The proportions of patients reaching HbA1c ≤ 7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively. Weight decreased with detemir [-0.49 (3.3) kg] and increased with glargine [+1.0 (3.1) kg] (95% CI for difference: -2.17 to -0.89 kg).. While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia.

Topics: Argentina; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Patient Satisfaction; Republic of Korea; Thailand; Treatment Outcome; United States

The goal of this study was to compare the long-term safety and efficacy of the basal insulin analogue, insulin degludec with insulin glargine (both with insulin aspart) in Type 1 diabetes, over a 2-year time period.. This open-label trial comprised a 1-year main trial and a 1-year extension. Patients were randomized to once-daily insulin degludec or insulin glargine and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l.. The rate of nocturnal confirmed hypoglycaemia was 25% lower with insulin degludec than with insulin glargine (P = 0.02). Rates of confirmed hypoglycaemia, severe hypoglycaemia and adverse events, and reductions in glycated haemoglobin and fasting plasma glucose were similar between groups. Despite achieving similar glycaemic control, insulin degludec-treated patients used 12% less basal and 9% less total daily insulin than did insulin glargine-treated patients (P < 0.01).. Long-term basal therapy using insulin degludec in Type 1 diabetes required lower doses and was associated with a 25% lower risk for nocturnal hypoglycaemia than insulin glargine.

Topics: Analysis of Variance; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Insulins; Male; Treatment Outcome

Avoidance of hypoglycemia is a key consideration in treating young children with type 1 diabetes (T1DM).. To evaluate hypoglycemia with insulin glargine vs. neutral protamine Hagedorn (NPH) insulin in young children, using continuous glucose monitoring (CGM).. Children of 1 to <6 yr treated with once-daily glargine vs. once- or twice-daily NPH, with bolus insulin lispro/regular human insulin provided to all.. Twenty-four week, multicenter, randomized, open-label study. Primary endpoint was event rate of composite hypoglycemia [symptomatic hypoglycemia, low CGM excursions (<3.9 mmol/L) or low fingerstick blood glucose (FSBG; <3.9 mmol/L)]. Noninferiority of glargine vs. NPH was assessed for the primary endpoint.. One hundred and twenty-five patients (mean age, 4.2 yr) were randomized to treatment (glargine, n = 61; NPH, n = 64). At baseline, mean HbA1c was 8.0 and 8.2% with glargine and NPH, respectively. Composite hypoglycemia episodes/100 patient-yr was 1.93 for glargine and 1.69 for NPH; glargine noninferiority was not met. Events/100 patient-yr of symptomatic hypoglycemia were 0.26 for glargine vs. 0.33 for NPH; low CGM excursions 0.75 vs. 0.72; and low FSBG 1.93 vs.1.68. There was a slight difference in between-group severe/nocturnal/severe nocturnal hypoglycemia and glycemic control. All glargine-treated patients received once-daily injections; on most study days NPH-treated patients received twice-daily injections.. While glargine noninferiority was not achieved, in young children with T1DM, there was a slight difference in hypoglycemia outcomes and glycemic control between glargine and NPH. Once-daily glargine may therefore be a feasible alternative basal insulin in young populations, in whom administering injections can be problematic.

Topics: Blood Glucose; Child; Child, Preschool; Circadian Rhythm; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Infant; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Monitoring, Ambulatory

This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.. In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups.. Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86).. Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles

The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes.. This open-label trial included a 52-week core period followed by a 52-week extension. Participants were randomized 3:1 to once-daily degludec or glargine, administered with metformin ± dipeptidyl peptidase-4 inhibitors. Basal insulin was titrated to target pre-breakfast plasma glucose 3.9-4.9 mmol/l.. At end of treatment (104 weeks), mean HbA1c reductions were similar for degludec and glargine; estimated treatment difference between degludec and glargine was 1 mmol/mol (95% CI -1 to 3) [0.07% (95% CI -0.07 to 0.22)], P = 0.339 in the extension trial set (degludec 551, glargine 174), comprising subjects who completed core trial and continued into the extension trial. Overall confirmed hypoglycaemia rates (1.72 vs. 2.05 episodes/patient-year), rates of adverse events possibly or probably related to trial product (0.19 events/patient-year), weight gain (2.7 vs. 2.4 kg) and mean daily insulin doses (0.63 U/kg) were similar between treatments in the safety analysis set (degludec 766, glargine 257) comprising all treated subjects. Rates of nocturnal confirmed hypoglycaemia (0.27 vs. 0.46 episodes/patient-year; P = 0.002) and severe hypoglycaemia (0.006 vs. 0.021 episodes/patient-year, P = 0.023) were significantly lower with degludec for the safety analysis set (analysis based on intention-to-treat full analysis set comprising all randomized subjects).. In Type 2 diabetes, insulin degludec in combination with oral anti-diabetic drugs, safely and effectively improves long-term glycaemic control, with a significantly lower risk of nocturnal hypoglycaemia as compared with glargine.

Topics: Administration, Oral; Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome

Hypoglycaemia caused by glucose-lowering therapy has been linked to cardiovascular (CV) events. The ORIGIN trial provides an opportunity to further assess this relationship.. A total of 12 537 participants with dysglycaemia and high CV-risk were randomized to basal insulin glargine titrated to a fasting glucose of ≤ 5.3 mmol/L (95 mg/dL) or standard glycaemic care. Non-severe hypoglycaemia was defined as symptoms confirmed by glucose ≤ 54 mg/dL and severe hypoglycaemia as a requirement for assistance or glucose ≤ 36 mg/dL. Outcomes were: (i) the composite of CV death, non-fatal myocardial infarction or stroke; (ii) mortality; (iii) CV mortality; and (iv) arrhythmic death. Hazards were estimated before and after adjustment for a hypoglycaemia propensity score. During a median of 6.2 years (IQR: 5.8-6.7), non-severe hypoglycaemic episodes occurred in 41.7 and 14.4% glargine and standard group participants, respectively, while severe episodes occurred in 5.7 and 1.8%, respectively. Non-severe hypoglycaemia was not associated with any outcome following adjustment. Conversely, severe hypoglycaemia was associated with a greater risk for the primary outcome (HR: 1.58; 95% CI: 1.24-2.02, P < 0.001), mortality (HR: 1.74; 95% CI: 1.39-2.19, P < 0.001), CV death (HR: 1.71; 95% CI: 1.27-2.30, P < 0.001) and arrhythmic death (HR: 1.77; 95% CI: 1.17-2.67, P = 0.007). Similar findings were noted for severe nocturnal hypoglycaemia for the primary outcome and mortality. The severe hypoglycaemia hazard for all four outcomes was higher with standard care than with insulin glargine.. Severe hypoglycaemia is associated with an increased risk for CV outcomes in people at high CV risk and dysglycaemia. Although allocation to insulin glargine vs. standard care was associated with an increased risk of severe and non-severe hypoglycaemia, the relative risk of CV outcomes with hypoglycaemia was lower with insulin glargine-based glucose-lowering therapy than with the standard glycaemic control. Trial Registration (ORIGIN ClinicalTrials.gov number NCT00069784).

Topics: Arrhythmias, Cardiac; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Prognosis; Risk Factors; Stroke

We explored the safety and efficacy of exenatide BID v. insulin glargine in a subgroup of Polish patients with type 2 diabetes sub-optimally controlled with metformin plus a sulfonylurea, participating in a 26-week randomised, controlled open-label trial.. In Poland, 80 patients (HbA1c 7-10%, BMI 25-45 kg/m(2)) were randomised to exenatide 10 μg BID (n = 40) or insulin glargine once daily (n = 40). We present exploratory analyses on HbA1c, glucose profiles, body weight, hypoglycaemia and adverse events (AEs).. Mean (SD) baseline HbA1c was 7.9% (0.86) for exenatide and 7.8% (1.02) for insulin glargine. At Week 26, LS mean (SEM) HbA1c decreased in both groups (exenatide -0.72% [0.12]; glargine -0.64% [0.12]), as did fasting glucose. Postprandial glucose excursions after breakfast and dinner were smaller in patients treated with exenatide. LS mean (SEM) body weight decreased by -1.9 (0.48) kg with exenatide and increased by 1.6 (0.48) kg with glargine (group difference [95%CI]: -3.5 kg [-4.9 to -2.2]). Hypoglycaemia was low in both groups; nocturnal hypoglycaemia was reported for three v. seven patients (three v. 24 episodes) in the exenatide and glargine groups, respectively. Adverse events were more common with exenatide (nausea n = 22 v. n = 1, vomiting n = 5 v. n = 0, headache n = 8 v. n = 2).. This exploratory analysis confirms that findings from the global study apply to patients treated with exenatide BID and glargine in Poland, showing that exenatide BID was as effective as insulin glargine. Data suggested that changes in HbA1c were similar, with fasting glucose changes greater in the glargine group and postprandial changes greater in the exenatide BID group. Exenatide BID was associated with weight reduction, less nocturnal hypoglycaemia, but more gastrointestinal events compared to glargine.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Glycated Hemoglobin; Headache; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Nausea; Peptides; Sulfonylurea Compounds; Venoms; Vomiting

Results of an exploratory phase 2 study showed that insulin degludec, a basal insulin with an action profile of longer than 42 h, provided similar glycaemic control when injected three times a week (IDeg 3TW) to once-daily insulin glargine (IGlar OD). To provide further evidence, we did two phase 3 trials to compare the efficacy and safety of IDeg 3TW with IGlar OD in insulin-naive patients with type 2 diabetes.. In two 26 week, randomised, open-label, parallel group, non-inferiority trials IDeg was injected Monday, Wednesday, and Friday before breakfast (IDeg 3TW(AM)) in the AM trial (94 sites in seven countries) or with the evening meal (IDeg 3TW(PM)) in the PM trial (89 sites in seven countries), and compared with IGlar OD. Adults with type 2 diabetes (HbA(1c) 7.0-10.0%; body-mass index ≤45 kg/m(2)) were randomly allocated (1:1) without stratification by a central interactive response system to IDeg 3TW or IGlar OD. Both groups continued taking metformin with or without dipeptidyl peptidase-4 inhibitors. Insulin was titrated to achieve a prebreakfast self-monitored blood glucose (SMBG) concentration of between 3.9 and less than 5.0 mmol/L. The primary outcome was non-inferiority of IDeg 3TW compared with IGlar OD, as assessed by change in HbA(1c) from baseline to 26 weeks (non-inferiority limit of 0.4%) by ANOVA in an intent-to-treat analysis (full analysis set). These trials are registered with ClinicalTrials.gov, numbers NCT01068678 and NCT01076647.. We recruited 460 patients for the AM trial (IDeg 3TW(AM), n=230; IGlar OD, n=230) and 467 patients for the PM trial (IDeg 3TW(PM), n=233; IGlar OD, n=234). After 26 weeks, mean HbA decreased by 0.9% (IDeg 3TW(AM)) and 1.3% (IGlar OD) in the AM trial, and by 1.1% (IDeg 3TW(PM)) and 1.4% (IGlar OD) in the PM trial. Non-inferiority was not confirmed in either trial (estimated treatment difference [IDeg 3TW(AM)-IGlar OD] 0.34%, 95% CI 0.18-0.51; [IDeg 3TW(PM)-IGlar OD] 0.26%, 0.11-0.41). Across the two trials, rates of confirmed hypoglycaemia (SMBG <3.1 mmol/L or severe [needing assistance]) ranged from 1.0 to 1.6 episodes per patient-year and were similar for IDeg 3TW(AM) and IGlar OD (estimated rate ratio [ERR] 1.04, 95% CI 0.69-1.55), but higher for IDeg 3TW(PM) than for IGlar OD (ERR 1.58, 1.03-2.43). The rate of nocturnal confirmed hypoglycaemia was higher for IDeg 3TW(AM) than for IGlar OD (ERR 2.12, 1.08-4.16); we noted no significant difference between IDeg 3TW(PM) and IGlar OD (ERR 0.60, 0.21-1.69).. The inferior glycaemic control and increased risk of hypoglycaemia with IDeg 3TW compared with IGlar OD do not support a three-times-weekly dosing regimen.. Novo Nordisk.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemia; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

Optimal dosing of basal insulin is needed to achieve target fasting blood glucose and to avoid hypoglycaemia on the other hand in patients of type 2 diabetes on bedtime basal insulin and daytime sulfonylureas. This is an open label, randomised prospective study done in 40 type 2 diabetics having uncontrolled diabetes. Statistical analysis was performed by the SPSS programme for windows, version 17.0. Continuous variables are presented as mean +/- SD, and categorical variables are presented as absolute numbers and percentage. Data were checked for normality before statistical analysis. Normally distributed continuous variables were compared from baseline to 12th week using paired t-test. The average dose requirement of insulin glargine was 33.55 +/- 11.94 units (mean +/- SD). The average insulin glargine dose requirement per kg body weight was 0.48 +/- 0.17 units/kg body weight. The range of insulin dose was 0.23 to 0.96 units/kg body weight. Dose titration is patient specific and should be done in order to achieve target fasting blood glucose.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Pioglitazone; Prospective Studies; Sulfonylurea Compounds; Thiazolidinediones

The effects of glargine/glulisine insulin regimen on exercise blood glucose (BG) and strategies to limit exercise-induced hypoglycemia are not well documented. Intermittent high-intensity exercise has been proposed to prevent hypoglycemia, but its effect in participants with type 1 diabetes using glargine/glulisine is unknown.. The study used a repeated-measures design with three randomly ordered exercise conditions. Eleven participants completed 60 min of moderate-intensity exercise at 50% VO(2peak) for all conditions. These conditions varied as follows: participants ingested 0 g of glucose preexercise (0G + MOD), 30 g of glucose preexercise (30G + MOD), or 0 g of glucose preexercise but performed brief high-intensity intervals interspersed every 2 min (0G + MOD/INT) during exercise. If BG fell <4 mmol·L(-1), a 20% dextrose solution was started to maintain BG between 4 and 5 mmol·L(-1).. Consuming 30 g of glucose before exercise (30G + MOD) resulted in a higher preexercise BG (11.7 ± 2.7 mmol·L(-1)) compared with 0 g of glucose before exercise (0G + MOD, 7.8 ± 4.0, and 0G + MOD/INT, 9.2 ± 3.5mmol·L(-1)), P < 0.05. A dextrose infusion was required in 7/11, 4/11, and 1/11 participants for 0G + MOD, 0G + MOD/INT, 30G + MOD conditions, respectively, P < 0.02. The duration and the quantity of dextrose infused were greatest in the 0G + MOD condition, moderate in the to 0G + MOD/INT condition, and minimal in the 30G + MOD condition, P < 0.01.. Our results suggest that both moderate-intensity exercise with a 30-g preexercise glucose beverage or interspersed with intermittent high-intensity sprints may be safe strategies to prevent hypoglycemia in glargine/glulisine users.

Topics: Adult; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Exercise; Exercise Test; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

Insulin glulisine (Glu) is a rapidly-acting insulin analog with a faster onset of action than the other insulin analogs of its class, which are insulin aspart (Asp) and insulin lispro (Lisp). While insulin Glu is usually injected just before meals, postprandial injection may help to avoid unexpected postprandial hypoglycemia or hyperglycemia by adjusting the insulin dosage according to food intake. However, the effect of postprandial insulin Glu on the glucose profile has not been evaluated. The aim of this study was to compare daily glucose excursion by continuous glucose monitoring (CGM) between multiple daily doses of preprandial insulin Asp or postprandial insulin Glu. In a randomized cross-over trial, we performed CGM to evaluate the 48-hour glucose profile during treatment with the same dosage of insulin Asp just before each meal in 12 hospitalized patients with type 2 diabetes. Patients also received the same dosage of long-acting insulin glargine at bedtime. The average glucose level, standard deviation of the glucose level, mean amplitude of glucose excursion, and daily glucose profile did not differ between preprandial Asp and postprandial Glu. The incidence of hypoglycemic episodes (glucose level<70 mg/dL with or without symptoms) and the area under the curve of glucose<70 mg/dL also did not differ between the two insulin regimens. Multiple daily injections of preprandial Asp and postprandial Glu achieved the same daily glucose excursion profile. Postprandial injection of Glu may provide greater flexibility for patients who require insulin therapy.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Monitoring, Ambulatory

Addition and titration of basal insulin is usually effective in improving glycaemic control in type 2 diabetes, but fear of hypoglycaemia remains a barrier. Ability to predict which patients might be at greatest risk of hypoglycaemia might facilitate individualization of treatment and improve safety. The aim of this study was to obtain information about clinical characteristics which might predict risk of hypoglycaemia during initiation of basal insulin.. Patient-level data from 2251 participants in 11 studies in which insulin glargine was started and titrated using similar treat-to-target methods was pooled and analysed with logistic regression models.. Participants had mean age 58 years, diabetes duration 8.9 years, body mass index 31.0 and baseline A1c 8.8%. They attained mean A1c 7.1% during 6 months of treatment with final mean glargine dosage 0.44 units/kg. Symptomatic hypoglycaemia occurred in 52%, glucose-confirmed hypoglycaemia (blood glucose <50 mg/dl) in 17%, repeated glucose-confirmed events in 7% and severe hypoglycaemia in 1.5%. Independent predictors of glucose-confirmed hypoglycaemia were younger age, lower body mass index, use of a sulphonylurea in addition to metformin, lower attained A1c and lower dosage of glargine.. These findings confirm low rates of clinically important hypoglycaemia using this method, and suggest that higher risk of hypoglycaemia may be suspected when patients needing insulin are younger, less obese and taking metformin and a sulphonylurea, and especially when A1c levels ≤7.0% are attained with glargine dosage ≤0.4 units/kg.

Topics: Age Factors; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Logistic Models; Male; Middle Aged; Overweight; Risk; Sulfonylurea Compounds

Degludec is a novel long-acting insulin analogue, providing an adequate supply of basal insulin over 24 hours with one daily injection, with a supposed greater reproducibility and flexibility than other basal insulins.. An extensive search of Medline and the Cochrane Library for 'degludec' was performed, up to July 1st, 2012, collecting all randomised trials with a duration of at least 16 weeks and enrolling patients with diabetes. The principal outcome was the effect of degludec, compared with other basal insulins, on endpoint HbA1c and hypoglycaemia. Secondary outcomes included BMI, FPG at endpoint, and the incidence of cardiovascular events and cancer.. In the four trials comparing degludec with glargine, endpoint HbA1c was similar in the two groups, whereas FPG was significantly lower in degludec-treated patients. Degludec was associated with a lower rate of overall and nocturnal hypoglycaemia in type 2 and type 1 diabetes, respectively. No differences were observed for cardiovascular events and cancer.. The number of available trials and the duration of exposure were limited, so the results obtained should be considered preliminary.. Degludec appears to be associated with a lower incidence of hypoglycaemia in comparison with glargine, for similar levels of glycaemic control. The use of this agent could represent one step further in insulin therapy.

Topics: Blood Glucose; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

To investigate the real-world use of combination insulin glargine/exenatide therapy for type 2 diabetes mellitus (T2DM) and associated treatment persistence and glycemic control.. In this retrospective study, data were extracted from a national US insurance claims database for patients with T2DM for whom insulin glargine and exenatide were co-prescribed in differing order: insulin glargine added after exenatide (EXE+); exenatide added after insulin glargine (GLA+); glargine and exenatide initiated together (GLA + EXE). Patients had continuous health plan coverage for 6 months pre- (baseline) and 1-year post-index (follow-up).. A total of 453 patients were eligible for analysis: 141 patients were included in the EXE+ cohort, 281 in the GLA+ cohort, and 31 in the GLA + EXE cohort. There were significant differences between the groups at baseline, including a significantly lower A1C in the GLA+ versus the EXE+ cohort (p = 0.0023). Around one third of patients stayed on both drugs up until the end of the follow-up period (GLA+: 30.2%; EXE+: 29.0%; GLA + EXE: 29.0%). However, more patients stayed on insulin glargine than on exenatide in each cohort. Significant A1C reductions were observed in each of the cohorts at follow-up: GLA+: -0.4%; EXE+: -0.9%; GLA + EXE: -1.2%; p < 0.01, and were significantly higher in the GLA + EXE and EXE+ cohorts than in the GLA+ cohort (p = 0.03 and p = 0.002, respectively). The mean number of hypoglycemic events increased slightly from baseline but remained low in each of the cohorts (GLA+: 0.12 to 1.42; EXE+: 0.09 to 1.04; GLA + EXE: 0.23 to 1.87 per patient, all p > 0.1).. Combined therapy with insulin glargine and exenatide resulted in A1C reductions in T2DM patients with poor glycemic control without a significantly increased risk of hypoglycemia irrespective of treatment order. Limitations of this study are the between-cohort differences at baseline, lack of a comparator group, and small n number, particularly in the GLA + EXE cohort.

Topics: Cohort Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Peptides; Retrospective Studies; Treatment Outcome; Venoms

To compare the safety and efficacy of adding insulin glargine or neutral protamine Hagedorn (NPH) insulin to existing oral antidiabetic drug (OAD) regimens in adults with type 2 diabetes mellitus.. Pooled analysis of data from five randomized controlled trials with similar designs.. Three hundred forty-two centers in more than 30 countries worldwide.. Randomly selected individuals aged ≤ 80 with a body mass index ≤ 40 kg/m(2) and a glycosylated hemoglobin (HbA1c) level of 7.5% to 12.0%.. Fixed- and random-effects models were used to compare outcomes after 24 or 28 weeks of treatment (insulin glargine, n = 1,441; NPH insulin, n = 1,254) according to age (≥65, n = 604 vs < 65, n = 2,091) and age based on treatment (e.g., ≥65 receiving insulin glargine vs NPH insulin). Outcomes included change in HbA1c, fasting blood glucose (FBG), insulin dose, and hypoglycemia incidence and event rates.. At end point, participants aged 65 and older receiving insulin glargine had greater reductions in HbA1c and FBG than those receiving similar doses of NPH insulin. In contrast, for participants younger than 65, there were no statistically significant differences in reductions in HbA1c or FBG between insulin glargine and NPH insulin. Daytime hypoglycemia rates were similar in all groups, although the rates of nocturnal symptomatic and severe hypoglycemia were lower with insulin glargine than NPH insulin.. Addition of insulin glargine to oral antidiabetic drugs in older adults with poor glycemic control may have modestly better glycemic benefits than adding NPH insulin, with low risk of hypoglycemia.

Topics: Adult; Age Distribution; Age Factors; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Global Health; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.. We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups.. The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97).. When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Fasting; Fatty Acids, Omega-3; Female; Follow-Up Studies; Glucose Intolerance; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Intention to Treat Analysis; Male; Middle Aged; Proportional Hazards Models; Triglycerides

Renal insufficiency may increase the risk of hypoglycemia in hospitalized patients with diabetes who are treated with insulin. We randomized inpatients with type 2 diabetes and chronic renal failure to treatment with two different dose levels of insulin glargine and glulisine and studied control of hyperglycemia and the frequency of hypoglycemia.. We conducted a multicenter, prospective, randomized trial to compare the efficacy of once-daily glargine and three-times daily glulisine at 0.5 vs. 0.25 units/kg/day. A total of 107 subjects had type 2 diabetes for >1 year, had a glomerular filtration rate <45 mL/min but did not require dialysis, and had an initial blood glucose (BG) >180 mg/dL. Doses were adjusted based on four-times daily BG measurements for 6 days.. Mean BG on the first day was 196 ± 71 mg/dL in the group receiving 0.5 units/kg (0.5 group) and 197 ± 55 mg/dL in the group receiving 0.25 units/kg (0.25 group; P = 0.94). On days 2 to 6, mean BG was 174 ± 52 mg/dL in the 0.5 group and 174 ± 46 mg/dL in the 0.25 group (P = 0.96). There were no significant differences between groups in the percentage of BG values within the target range of 100 to 180 mg/dL on any of the 6 study days. In the 0.5 group, 30% experienced hypoglycemia (BG <70 mg/dL) compared with 15.8% of the 0.25 group (P = 0.08).. Reduction of initial glargine/glulisine insulin weight-based dosing in hospitalized patients with diabetes and renal insufficiency reduced the frequency of hypoglycemia by 50% without compromising the control of hyperglycemia.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Renal Insufficiency; Treatment Outcome

Information on starting insulin regimens in specific populations with type 2 diabetes (T2D) is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25) and basal insulin glargine (GL) in patients from Argentina. This post-hoc analysis evaluated 193 insulin-naïve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0%) with = 2 oral antihyperglycemic medications (OAMs), were randomized to add LM25 (25% insulin lispro, 75% insulin lispro protamine suspension) twice daily or GL (basal insulin glargine) once daily to pre-study OAMs. Primary efficacy was measured by HbA1c at 24-week endpoint. Secondary measures included: proportion of patients achieving HbA1c = 6.5% and = 7.0%, body weight change, self-monitored blood glucose (BG) values, and hypoglycemia rates. LM25 demonstrated greater HbA1c reduction (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), a higher proportion of patients achieving HbA1c = 7.0% (P = 0.012), and lower BG levels after the morning (P = 0.028) and evening (P = 0.011) meals, and at 3:00AM (P = 0.005) compared with GL. Fasting BG and proportion of patients achieving HbA1c = 6.5% were similar between groups. Both groups increased body weight, although the gain was higher at endpoint with LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No differences in hypoglycemia rates were observed between groups, and no serious adverse events were reported for either group. In this subgroup from Argentina, LM25 demonstrated greater improvement in glucose control with similar risk of hypoglycemia and more weight gain than GL.

Topics: Adult; Aged; Argentina; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Weight Gain

In patients with diabetes, intraday glucose variability might predict health outcomes independently from glycosylated hemoglobin (HbA1c).. Our objective was to evaluate patient satisfaction (PS), quality of life (QoL), glycemic control, and variability during insulin intensification to HbA1c below 7.0%.. Eighty-two type 1 and 306 insulin-treated type 2 diabetes patients (47% male; age 54±11 yr; HbA1c=7.8±0.7%) participated in this multicenter, randomized, crossover trial at 52 U.S. centers.. Interventions included insulin glargine plus premeal glulisine (n=192) vs. twice-daily premix 75/25 or 70/30 analog insulin (n=196) for 12 wk and crossed to the alternate arm for 12 wk.. Main outcome measures included PS and QoL questionnaires, 3-d continuous glucose monitoring (CGM), and HbA1c every 4-8 wk.. Mean±se HbA1c change was -0.39±0.09% for glargine-glulisine and -0.05±0.09% for premix (P<0.0001). The PS net benefit scale (0-100) improved from 51.1 to 60.5±1.2 for glargine-glulisine and worsened to 45.4±1.2 for premix (P<0.0001). The PS regimen acceptance scale was comparable (P=0.33). Overall QoL favored glargine-glulisine (P<0.001), as did perceived health (P<0.0001), symptom distress (P<0.0001), general health perceptions (P<0.01), and psychosocial (P<0.02). CGM daily glucose mean, daily glucose sd (glycemic variability), and percent time over 140 mg/dl were lower for glargine-glulisine by 13.1±2.7 mg/dl, 5.9±1.4 mg/dl, and 7.3±1.6%, respectively (all P<0.0001), with no difference in CGM percent time below 70 mg/dl (P=0.09). Symptomatic hypoglycemia rates were comparable. HbA1c, mean CGM daily glucose, and glycemic variability were independent predictors of PS net benefit.. Patient satisfaction was impacted more positively by improved QoL, reduced glucose variability, and better glycemic control with a basal-bolus regimen than negatively by the burden of additional injections, thereby facilitating insulin intensification and the ability to achieve HbA1c below 7.0%.

Topics: Adult; Aged; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires

Exenatide once weekly (QW) is an extended-release formulation of exenatide, a glucagon-like peptide-1 receptor agonist that reportedly improves glycemic control in patients with type 2 diabetes.. The goal of this study was to test the hypothesis that exenatide QW is noninferior to insulin glargine, as measured by change in glycosylated hemoglobin (HbA(1c)) from baseline to end point (week 26 [primary end point]) in Japanese patients with type 2 diabetes who have inadequate glycemic control with oral antidiabetes drugs.. In this open-label, parallel-group, multicenter, noninferiority registration study, patients were randomized (1:1) to add exenatide QW (2 mg) or once-daily insulin glargine (starting dose, 4 U) to their current oral antidiabetes drug treatment. The primary analysis was change in HbA(1c) from baseline to end point, evaluated by using a last-observation-carried-forward ANCOVA model, with a predefined noninferiority margin of 0.4%. Secondary analyses (a priori) included analysis of superiority for between-group comparisons of change in weight and the proportion of patients reaching HbA(1c) target levels of ≤7.0% or ≤6.5%.. The baseline characteristics of the exenatide QW (215 patients) and insulin glargine (212 patients) treatment groups were similar: mean (SD) age, 57 (10) years and 56 (11) years, respectively; 66.0% and 69.8% male; mean HbA(1c), 8.5% (0.82%) and 8.5% (0.79%); and mean weight, 69.9 (13.2) kg and 71.0 (13.9) kg. Exenatide QW was statistically noninferior to insulin glargine for the change in HbA(1c) from baseline to end point (least squares mean difference, -0.43% [95% CI, -0.59 to -0.26]; P < 0.001), with the 95% CI upper limit less than the predefined noninferiority margin (0.4%). A significantly greater proportion of patients receiving exenatide QW compared with insulin glargine achieved HbA(1c) target levels of ≤7.0% (89 of 211 [42.2%] vs 44 of 210 [21.0%]) or ≤6.5% (44 of 214 [20.6%] vs 9 of 212 [4.2%]) at end point (P < 0.001 for both). Patient weight was reduced with exenatide QW compared with insulin glargine at end point (least squares mean difference, -2.01 kg [95% CI, -2.46 to -1.56]; P < 0.001). Exenatide QW was well tolerated, with a lower risk of hypoglycemia compared with insulin glargine but a higher incidence of injection-site induration.. Exenatide QW was statistically noninferior to insulin glargine for the change in HbA(1c) from baseline to end point; these results suggest that exenatide QW may provide an effective alternative treatment for Japanese patients who require additional therapy to control their diabetes. ClinicalTrials.gov identifier: NCT00935532.

Topics: Administration, Oral; Aged; Blood Glucose; Body Weight; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Japan; Least-Squares Analysis; Male; Middle Aged; Peptides; Venoms

To investigate an effective and safe protocol for enteral nutrition (EN) patients permitting successfully transmit insulin administration from venous pump-in to subcutaneous injection.. A prospective randomized control study was conducted. Critical patients admitted to intensive care unit (ICU) of Beijing Tongren Hospital from September 2008 to February 2009 were randomly divided into two groups when the energy provided by EN up to half of the total energy requirement. Experiment group (n=44): the protocol was applied for insulin glargine and regular insulin injection; control group (n=43): protocol was applied for subcutaneous regular insulin injection. Target glucose range was 4.4-7.8 mmol/L (80-140 mg/dl). If blood glucose ≥11.1 mmol/L was maintained twicely, the approach of insulin administration would convert from subcutaneous injection to venous pump-in using the computerized glucose control protocol. If the infusion rate of insulin was less than 3 U/h and lasted more than 6 hours, blood glucose ≤7.8 mmol/L, insulin administration was switched to subcutaneous injection again. The general information and all glucose regulation data were recorded for analysis.. The two groups did not differ at baseline for the general information, mean blood glucose and the glucose variation. A total of 1689 blood glucose records were analyzed. The mean blood glucose in experiment group, and was significantly lower than that in control group(7.58±1.17 mmol/L vs. 9.40±1.74 mmol/L, P<0.05). The rate of glucose values within target range in experiment group was significantly higher than that in control group [49.72% (534/1074) vs. 35.61% (219/615), P<0.01]. The glucose standard deviation (SD) in experiment group was significantly lower than that in control group (1.89±0.52 mmol/L vs. 2.17±0.94 mmol/L, P<0.05). The number of measurements needed per patient per day was significantly reduced in experiment group compared with control group (7.51±1.31 vs. 8.15±0.97, P<0.05). The ratio of patients converted to venous pump-in was significantly decreased in experiment group compared with control group (9.09% vs. 44.19%, P<0.01). Hypoglycemia (≤3.3 mmol/L) did not different between experiment group and control group [0.74% (8/1074) vs. 0.49% (3/615), P=0.75].. Compared with the conventional subcutaneous insulin injection protocol, this protocol with insulin glargine combined regular insulin subcutaneous injection can control the glucose level effectively during EN in critical patients. The glucose variation and the numbers of measurements were significantly reduced by this protocol. It is helpful for the insulin transmission from venous pump-in to subcutaneous injection.

Topics: Adult; Aged; Blood Glucose; Critical Illness; Enteral Nutrition; Female; Humans; Hyperglycemia; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Intensive Care Units; Male; Middle Aged; Prospective Studies

In this randomized, single blind, cross-over study 2.5 mg and 5 mg of the modified-release terbutaline formulation (SKP-1052) were compared with conventional immediate-release terbutaline (IRT, 5 mg) and placebo on overnight blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes mellitus.. Subjects received subcutaneous injections of insulin glargine (individualized doses) before dinner. SKP-1052, IRT or placebo was administered around 21:00 hours. BG and terbutaline concentrations were monitored overnight for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0-10 h, primary endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia rates as well as pharmacokinetic (PK) endpoints.. SKP-1052 delayed release of terbutaline by 2 h [PK-tmax (mean ± SD) 5.0 ± 2.1 h (2.5 mg) and 4.7 ± 1.7 h (5 mg) vs. 2.6 ± 1.3 h with IRT, p < 0.01, respectively]. Compared with placebo, no significant differences were observed for BGn 0-10 h across treatments, but both 5 mg formulations showed less hypoglycaemic events [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95 mg/dl) and BGmorning (126, 126 and 101 mg/dl, all comparisons p < 0.05 vs. placebo). Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5 mg SKP-1052 vs. placebo.. Compared with IRT SKP-1052 delays release of terbutaline. 2.5 mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting hyperglycaemia vs. placebo. Future studies will investigate optimized doses of SKP-1052 for nocturnal hypoglycaemia prevention.

Topics: Adolescent; Adult; Blood Glucose; Cross-Over Studies; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Fasting; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Single-Blind Method; Terbutaline

The aim of this study was to compare coefficient of variation of fasting capillary blood glucose (FBG) between insulin glargine and NPH in T2DM with poorly controlled by oral antidiabetic drugs. The results demonstrated that insulin glargine was more potent in improving glycemic control than NPH with stable FBG.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Homeostasis; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin-Secreting Cells; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

No study of transition from intravenous to subcutaneous insulin after cardiac surgery with dose based on percentage of intravenous total daily insulin (TDI) has reported a clearly superior regimen for achieving target blood glucose. We compared three first-dose transition strategies for insulin glargine: two based on TDI alone and one that also took body weight into account.. Mostly obese, type 1 and type 2 diabetes patients (n = 223) undergoing cardiac surgery were randomized to receive insulin glargine subcutaneously at 60% or 80% of TDI or in a dose based on TDI and body weight.. Transition to subcutaneous insulin occurred 27.4 ± 6.6 h after surgery. Over the study period, mean proportion of blood glucose values within target range (80-140 mg/dL) were 0.34 ± 0.24, 0.35 ± 0.24, and 0.36 ± 0.22 in the 60% TDI, 80% TDI, and weight-based groups, respectively. This difference was not significant. Significantly more insulin corrections were needed in the 60% TDI group than in the weight-based group. There was only one incidence of hypoglycemia (blood glucose < 40 mg/dL).. No subcutaneous insulin regimen implemented approximately 1 day after cardiac surgery showed significantly better control of blood glucose over the 3-day study period. Further studies are needed to determine optimal formulae for effecting an early transition to subcutaneous insulin after cardiac surgery or whether it is preferable and/or necessary to continue intravenous insulin therapy for an additional period of time.

Topics: Aged; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity; Postoperative Care

In diabetes, endothelial damage promotes macroangiopathy and endothelial regeneration is impaired, owing to reduced endothelial progenitor cells (EPCs). Given that insulin influences endothelial biology, we compared the effects of add-on basal insulin analogues on endothelial damage and regeneration in type 2 diabetes (T2D).. This was a 6-month randomized crossover trial comparing add-on insulin detemir versus glargine in poorly controlled T2D with macroangiopathy. At baseline, crossover (3 months) and study end (6 months), we measured HbA1c, EPCs, circulating endothelial cells (CECs), VCAM-1, ICAM-1 and E-selectin. Body weight and hypoglycaemic episodes were also recorded.. Forty-two patients completed the study, randomly assigned to the glargine-detemir (n = 21) or the detemir-glargine (n = 21) schedule. At crossover, EPC levels did not change compared with baseline, but significantly increased at study end. CECs decreased over time and were significantly reduced at study end. ICAM-1, VCAM-1 and E-selectin were significantly reduced at crossover and further decreased at study end. No differences were seen in these effects between detemir and glargine. HbA1c showed a carryover effect and its reduction was similar with detemir and glargine in the first arm. Incidence of hypoglycaemia and weight gain was lower with detemir than with glargine in both arms.. Optimized glycaemic control by add-on basal insulin improved indexes of endothelial damage and regeneration. Compared to glargine, detemir achieved similar endothelial protection with lower weight gain and less hypoglycaemia. These results might have implications for therapy of aging T2D patients with cardiovascular disease.

Topics: Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Endothelial Cells; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks and HbA1c ≤ 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c ≤ 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Off-Label Use; Pregnancy; Pregnancy in Diabetics

Prolonged fasting may be necessary in life for religious, medical and other reasons. For this reason, our study investigated the feasibility and safety of a 24-h fast conducted at home for patients with type 1 diabetes.. Thirty-four patients with type 1 diabetes performed a 24-h complete fast at home. Thirteen patients were treated with multiple insulin injections using either glargine (n=12) or NPH (n=1) as basal insulin. The remaining patients were treated with an insulin pump. All patients received their basal insulin only, which was adjusted to 40% of their total daily dose, and were monitored by either a Gold(®) or Guardian(®) continuous glucose monitoring (CGMS) device. Capillary glucose (SMBG) was targeted at 3.9-7.8 mmol/L, with a standardized protocol for correction of hyper- and hypoglycaemia. Interstitial glucose (IG) profiles were compared with the SMBG values; the IG profiles of patients using glargine or a pump and either of the two CGMS devices were also compared.. All of the patients completed the 24-h fast with no major incident. At the end of the fast, 80% of the IG values were on target. The route by which insulin was delivered made no difference, but there were more IG values on target in patients monitored by the Guardian(®) device. IG was below target in 104 occurrences and above-target in 34. After a mean intake of 10 g of sucrose, below-target IG was corrected within 30 min [range: 15-40]. The mean insulin dose to correct above-target episodes was 1 U.. Prolonged fasting is possible at home in patients with type 1 diabetes, provided the basal dose is adjusted. The use of CGMS is not necessary, but offers useful information on the patient's IG profile during the fast.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Drug Administration Schedule; Fasting; Feasibility Studies; Female; Guideline Adherence; Guidelines as Topic; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Time Factors

To determine the functional health status and treatment satisfaction in patients with type 2 diabetes from the Evaluation of Lantus Effect ON Optimization of use of single dose Rapid insulin (ELEONOR) study that investigated whether a telecare program helps optimization of basal insulin glargine with one bolus injection of insulin glulisine.. Functional health status and treatment satisfaction were investigated using the 36-Item Short-Form (SF-36) Health Survey, the World Health Organization Well-Being Questionnaire (WBQ), and the Diabetes Treatment Satisfaction Questionnaire.. Of 291 randomized patients, 238 completed the study (telecare: 114; self-monitoring blood glucose: 124). Significant improvements were detected in most SF-36 domains, in WBQ depression and anxiety scores, and in treatment satisfaction, without differences between study groups.. An insulin regimen that substantially improves metabolic control, while minimizing the risk of hypoglycemia, can positively affect physical and psychologic well-being and treatment satisfaction irrespective of the educational support system used.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Patient Satisfaction; Quality of Life; Telecommunications; Treatment Outcome

To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes.. In this double-blind study, 587 patients taking stable-dose insulin glargine (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) to MK-0941 10, 20, 30, or 40 mg or matching placebo t.i.d. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week treatment phase during which patients were to be uptitrated as tolerated to 40 mg (or placebo) t.i.d. a.c. The primary efficacy end point was change from baseline in A1C at Week 14.. At Week 14, A1C and 2-h postmeal glucose (PMG) improved significantly versus placebo with all MK-0941 doses. Maximal placebo-adjusted least squares mean changes from baseline in A1C (baseline A1C 9.0%) and 2-h PMG were -0.8% and -37 mg/dL (-2 mmol/L), respectively. No significant effects on fasting plasma glucose were observed at any dose versus placebo. By 30 weeks, the initial glycemic responses noted at 14 weeks were not sustained. MK-0941 at one or more doses was associated with significant increases in the incidence of hypoglycemia, triglycerides, systolic blood pressure, and proportion of patients meeting criteria for predefined limits of change for increased diastolic blood pressure.. In patients receiving stable-dose insulin glargine, the GKA MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood pressure.

Topics: Adult; Aged; Benzamides; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Enzyme Activators; Glucokinase; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Sulfones

Once-daily (OD) basal insulin glargine (GLA) can be used as part of a multiple daily injection regimen in patients with type 1 diabetes mellitus. This randomized, multicenter study compared GLA+prandial regular human insulin (RHI) with GLA+prandial insulin lispro (LIS) in reducing the incidence of severe nocturnal hypoglycemia at endpoint. In addition, the effects on glycemic control of both treatments were investigated.. Patients (489) previously on neutral protamine Hagedorn (NPH) insulin or GLAR plus RHI/LIS were switched to, or continued on GLA (target fasting blood glucose [FBG]=5.0-6.7 mmol/L [90-120 mg/dL]) for 8 weeks (qualification phase) prior to randomization; patients continued with their previous bolus insulin. Patients (n=395) were then randomized to LIS (n=193) or RHI (n=202) and treated for 16 weeks. The proportion of patients experiencing severe nocturnal hypoglycemia at the end of the study was 1.55% (n=3) in the RHI group and 1.11% (n=2) in the LIS group (p=0.938 between groups); the mean difference was 0.44% (95% CI: -1.77, 2.21), suggesting non-inferiority of RHI versus LIS. At the end of the study, both treatments did not differ with respect to glycemic control, as measured by hemoglobin A(1c) and FBG.. These results suggest that GLA+LIS and GLA+RHI treatments were associated with a similar and low rate of severe nocturnal hypoglycemia. Further studies with greater patient sizes are necessary to verify the findings from the current study.

Topics: Adult; Biomarkers; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Italy; Male; Middle Aged; Severity of Illness Index; Time Factors; Treatment Outcome

We compare the efficacy and safety of once-daily biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine in Asian subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs (OADs). In a 26-week, open-labelled, randomised, parallel-group, multinational, multicentre, treat-to-target trial, 155 insulin-naïve Asian subjects were treated with either BIAsp 30 or insulin glargine, both in combination with metformin and glimepiride. Change in HbA(1c) at end of treatment with BIAsp 30 was superior to insulin glargine (BIAsp 30-glargine=-0.36%, 95% CI [-0.64; -0.07], p=0.015). Mean self-measured plasma glucose (SMPG) at bedtime was significantly lower with BIAsp 30 than insulin glargine (7.98+/-0.34 mmol/L vs. 9.16+/-0.33 mmol/L, p=0.0078). Incidences of minor and daytime hypoglycaemia were higher with BIAsp 30 than those with glargine, but the difference did not reach the statistical significance. No difference was seen in nocturnal hypoglycaemia. The incidence of adverse events was comparable between treatments, with low incidence of serious adverse events and major hypoglycaemia. Mean body weight increased slightly in both groups. In insulin-naïve Asian subjects with type 2 diabetes who are inadequately controlled with OADs, once-daily BIAsp 30 is superior to insulin glargine.

Topics: Administration, Oral; Adolescent; Adult; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Dosage Forms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; International Agencies; Male; Middle Aged; Treatment Outcome; Young Adult

The purpose of this sub-study of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial was to determine efficacy and safety of targeting normal fasting plasma glucose (FPG) levels in patients with early Type 2 diabetes treated with insulin glargine in comparison with standard care.. Participants were randomly allocated to insulin or standard care. Insulin was titrated to reach FPG

Topics: Adult; Aged; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period

Current guidelines for dietary management of Type 1 diabetes in children recommend a carbohydrate supper before bed. However, with the introduction of insulin analogues such as glargine (with a basal insulin profile), supper may be unnecessary. The purpose of this study was to investigate whether supper is required to prevent nocturnal hypoglycaemia when using multiple daily injections, with glargine as the basal insulin and rapid-acting insulin pre-meals, in older children with Type 1 diabetes.. Thirty-five children aged 10-18 years with Type 1 diabetes were recruited to a randomized cross-over trial (supper vs. no supper). Each phase consisted of three consecutive days of wearing a continuous glucose-monitoring system (CGMS) to record nocturnal blood glucose levels in the home setting. The supper phase included one 15-g carbohydrate dairy snack consumed before bed. The evening meals were standardized. Activity was restricted.. Valid CGMS data were obtained for 163 nights (85 supper, 78 no supper). Nocturnal hypoglycaemia rates were similar in the supper and no-supper groups (32.9% vs. 33.3% of nights; P = 0.96).. This study suggests that supper is not necessary for all children to prevent nocturnal hypoglycaemia when using glargine insulin. The recommendation for inclusion of supper should be individually tailored and not mandatory.

Topics: Adolescent; Blood Glucose; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Dietary Carbohydrates; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Time Factors

Insulin therapy is often a delayed strategy in patients with type 2 diabetes mellitus because it is associated with weight gain, hypoglycaemia, and the need for subcutaneous injections. We aimed to assess the efficacy and safety of prandial Technosphere inhaled insulin compared with twice daily biaspart insulin.. In this randomised, open-label, parallel-group study, adult patients with type 2 diabetes mellitus and poor glycaemic control despite insulin therapy, with or without oral antidiabetes drugs, were enrolled from ten countries between Feb 23, 2006, and Aug 8, 2007. Patients were randomly allocated in a 1:1 ratio to receive 52 weeks' treatment with: prandial Technosphere inhaled insulin powder plus bedtime insulin glargine; or twice daily premixed biaspart insulin (70% insulin aspart protamine suspension and 30% insulin aspart of rDNA origin). The primary endpoint was a comparison of change in glycosylated haemoglobin (HbA(1c)) from baseline to week 52 between treatment groups; the non-inferiority margin was 0.4%. Analysis was by per protocol for non-inferiority testing of the primary endpoint. This study is registered with ClinicalTrials.gov, number NCT00309244.. 334 patients were allocated to inhaled insulin plus insulin glargine, and 343 to biaspart insulin; 107 patients on inhaled insulin plus insulin glargine and 85 on biaspart insulin discontinued the trial. 211 patients on inhaled insulin plus insulin glargine and 237 on biaspart insulin were included in per-protocol analyses. Change in HbA(1c) with inhaled insulin plus insulin glargine (-0.68%, SE 0.077, 95% CI -0.83 to -0.53) was similar and non-inferior to that with biaspart insulin (-0.76%, 0.071, -0.90 to -0.62). The between-group difference was 0.07% (SE 0.102, 95% CI -0.13 to 0.27). Patients had significantly lower weight gain and had fewer mild-to-moderate and severe hypoglycaemic events on inhaled insulin plus insulin glargine than on biaspart insulin. The safety and tolerability profile was similar for both treatments, apart from increased occurrence of cough and change in pulmonary function in the group receiving inhaled insulin plus insulin glargine.. This study is part of a large clinical development programme addressing the efficacy and tolerability of use of Technosphere inhaled insulin in a wide variety of patients.. MannKind.

Topics: Administration, Inhalation; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Powders

The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen.. This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was administered first with fixed dose and injection times and then adapted to optimal dose after 3 months.. Mean HbA(1c) (%) of all the subjects at months 4 to 6 of the study was improved compared with month 0 (7.34 ± 0.87, 7.28 ± 0.88, 7.25 ± 0.93 vs. 7.55 ± 1.18; p < 0.05 paired t-test). However, significant improvement was seen only among the patients who had previously used NPH as a basal insulin. Twice-daily injection of basal insulin increased among people in the type 1 previously injected insulin glargine. Total insulin dose increased in the type 1 glargine group. The mean body weight change in the highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6 months. Quality of life (QoL) relating to the patients' glycaemic control tended to improve without a change in frequency of hypoglycaemia.. The results suggest that insulin detemir has a greater effect on glycaemic control in subjects with poor glycaemic control using NPH; can reduce or maintain body weight in obese patients; and obtains perceptive stability for patients with unstable glycaemic control.

Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Obesity; Prospective Studies; Treatment Outcome; Weight Loss

To compare switching from NPH insulin (NPH) to insulin glargine (glargine) with continuing NPH for changes in fasting blood glucose (FBG) in patients with Type 1 diabetes on basal-bolus therapy with insulin lispro as bolus insulin. Secondary objectives included self-monitoring blood glucose, mean daily blood glucose (MDBG) and mean amplitude glucose excursion (MAGE) values alongside changes in HbA(1c) and safety profiles.. This was a 30-week, parallel, open-label, multicentre study. Seven-point profiles were used to calculate MDBG and MAGE. Hypoglycaemia and adverse events were recorded by participants. FBG improved significantly with both glargine (baseline-endpoint change: -28.0 mg/dL; 95% CI: -37.3, -18.7 mg/dL; p<0.001) and NPH (-9.8 mg/dL; 95% CI: -19.1, -0.5 mg/dL; p=0.0374). The improvement was significantly greater with glargine than NPH (mean difference: -18.2 mg/dL; 95% CI: -31.3, -5.2 mg/dL; p=0.0064). MDBG (-10.1 mg/dL; 95% CI: -18.1, -2.1 mg/dL; p=0.0126) and MAGE (-20.0 mg/dL; 95% CI: -34.5, -5.9 mg/dL; p=0.0056) decreased significantly with glargine, but not NPH although endpoint values were no different with the two insulins. Baseline to endpoint change in HbA(1c) was similar (-0.56 vs -0.56%) with no differences at endpoint. Overall hypoglycaemia was no different, but glargine reduced nocturnal hypoglycaemia ("serious episodes" with BG < 42 mg/dl, p=0.006) whereas NPH did not (p=0.123), although endpoint values were no different.. Switching from NPH to glargine is well tolerated and results into lower FBG, and lower glucose variability while reducing nocturnal hypoglycaemia. These data provide a rationale for more aggressive titration to target with glargine in Type 1 diabetes.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Circadian Rhythm; Diabetes Mellitus, Type 1; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Italy; Male; Middle Aged; Quality of Life; Treatment Outcome; Young Adult

This randomised, open-label, two-way cross-over study compared the coefficient of variance (CV) of fasting and postprandial blood glucose (FBG and PPBG) with insulin glargine (glargine) versus neutral protamine Hagedorn (NPH) insulin treatment in patients with Type 2 diabetes (T2DM). Patients (N=20) on oral antidiabetic drugs (OADs) were treated with NPH (at bedtime) or glargine (at dinnertime) for 12 weeks of each cross-over treatment period; OADs were continued. The FBG CV was calculated from self-monitored BG values and PPBG using venous blood samples, or continuous glucose monitoring system (CGMS). Both insulins provided similar improvements in glycaemic control; however, PPBG was significantly lower after a standard meal test (performed at 13:00 h the day after insulin injection) with glargine versus NPH (p=0.02). Thirteen versus 15 patients experienced >or=1 episode of hypoglycaemia with glargine versus NPH. The results suggest that glargine plus OADs is more effective in reducing PPBG fluctuations during the day than NPH plus OADs.

Topics: Administration, Oral; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Monitoring, Ambulatory; Pilot Projects

To determine whether earlier administration of insulin glargine (glargine) vs. the intensification of lifestyle management (LM) improves glycaemic control in type 2 diabetes patients with A1c 7-8% treated with oral therapy.. TULIP [Testing the Usefulness of gLargine when Initiated Promptly in type 2 diabetes mellitus (T2DM)] was a 9-month, 12-visit, open-label, multinational, multicentre, randomized study to evaluate starting glargine or intensifying LM in T2DM patients aged 40-75 years, body mass index (BMI) 24-35 kg/m2 and A1c 7-8%, treated with maximum doses of metformin and sulphonylurea for > or = 2 years. Glargine was injected once daily (evening) and titrated to fasting blood glucose 0.7-1.0 g/l. In the LM arm, dietary and physical activity counselling recommended stable weight for people with BMI < 27 kg/m2 or weight loss of 3 kg for patients with BMI > or = 27 kg/m2. A total of 215 patients were randomized to glargine (n = 106) or LM (n = 109). The primary objective was patients achieving A1c < 7% at endpoint. Secondary endpoints included changes in A1c, in fasting plasma glucose (FPG), body weight and hypoglycaemia incidence.. Two hundred and eleven (52.6% male) patients were randomized and treated; mean (+/- s.d.) age 60.7 +/- 7.9 years, weight 84.5 +/- 13.1 kg, BMI 29.9 +/- 3.5 kg/m2 and A1c 7.6 +/- 0.4%. More patients reached A1c < 7% (66 vs. 38%; p < 0.0001) or < 6.5% (34 vs. 11%; p = 0.0001) with glargine vs. LM. The change in FPG from baseline to study endpoint was significantly greater in the glargine vs. the LM arm (-0.50 +/- 0.47 vs. -0.05 +/- 0.39 g/l respectively; p < 0.0001). Compared with the glargine group, the LM group showed a decrease in weight (+0.9 +/- 2.9 vs. -2.5 +/- 3.2 kg; p < 0.0001), as well as the expected lower symptomatic hypoglycaemia (55.3 vs. 25.0%; p < 0.0001) and nocturnal hypoglycaemia (20.4 vs. 5.6%; p = 0.0016). No significant changes were observed from baseline to study endpoint in any of the lipid parameters tested.. In patients with T2DM with A1c 7-8%, who were previously treated by conventional LM and OAD therapy, adding glargine resulted in greater improvements in glycaemic control vs. intensifying LM.

Topics: Adult; Aged; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Life Style; Middle Aged; Treatment Outcome

To examine the relationship between glycaemic control and hypoglycaemia in patients with type 2 diabetes treated with metformin (Met) and either insulin lispro mixtures, given twice or thrice daily (LM + Met), or insulin glargine, given once daily (G + Met).. Data from three randomized clinical trials were pooled to compare effects of LM + Met with G + Met.. The LM + Met group achieved lower mean HbA(1c) (mean+/-SE, 7.2+/-0.1 vs. 7.7+/-0.1%, p<0.0001) and all meals combined post-prandial blood glucose (BG) (8.9+/-0.1 vs. 10.2+/-0.1 mmol/L, p<0.0001) compared with the G + Met group, but had higher fasting blood glucose (8.1+/-0.1 vs. 6.8+/-0.1 mmol/L, p<0.0001) and insulin requirement (0.7+/-0.01 vs. 0.6+/-0.01 U/kg, p<0.0001). Over the entire study period, daytime hypoglycaemia was higher for the LM + Met group (10.3 vs. 3.5 episodes/patient/year, p<0.0001) than for the G + Met group; however, nocturnal hypoglycaemia was lower (3.4 vs. 6.6 episodes/patient/year, p=0.003). At endpoint, daytime hypoglycaemia was higher for the LM + Met group (6.2 vs. 1.4 episodes/patient/year, p<0.0001); however, nocturnal hypoglycaemia was similar in both groups (1.9 vs. 3.0 episodes/patient/year). An inverse relationship was observed between all confirmed hypoglycaemia and HbA(1c) at endpoint; for every 1% reduction in HbA(1c), the increase (in slope) was 1.4 episodes/patient/year (p=0.04). Patients with confirmed hypoglycaemia had lower HbA(1c) than patients without hypoglycaemia (7.39 vs. 7.64%, respectively; decrement=0.26%, p=0.026).. These studies demonstrated an inverse relationship between HbA(1c) and 24-h and daytime hypoglycaemia. Lispro insulin mixtures provided lower HbA(1c) and post-prandial blood glucose values than glargine, but caused more daytime hypoglycaemia. Frequency of nocturnal hypoglycaemia was similar and severe hypoglycaemia was rare with both insulin regimens.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Metformin; Middle Aged

To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT).. Fifty inpatients were prospectively randomized to receive sliding-scale regular insulin (SSRI) alone (n = 25) or in combination with insulin glargine (n = 25). NPH insulin was added for persistent hyperglycemia in the SSRI group (glucose >10 mmol/l).. Glycemic control was similar in the SSRI and glargine groups (mean +/- SD study glucose 8.9 +/- 1.6 vs. 9.2 +/- 1.6 mmol/l, respectively; P = 0.71). NPH insulin was added in 48% of the SSRI group subjects. There were no group differences in frequency of hypoglycemia (1.3 +/- 4.1 vs. 1.1 +/- 1.8%; P = 0.35), total adverse events, or length of stay.. Both insulin strategies (SSRI with the addition of NPH for persistent hyperglycemia and glargine) demonstrated similar efficacy and safety in non-critically ill hospitalized patients with type 2 diabetes during ENT.

Topics: Aged; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Severity of Illness Index

Combinations of insulin and oral antidiabetic drugs (OAD) are often prescribed instead of insulin alone. In this study, the effects of insulin glargine (IG) in combination with repaglinide or acarbose on glycemic parameters were investigated. Obese Type 2 diabetic patients with fasting blood glucose (FBG) levels >or= 7.7 mmol/l [corrected] and hemoglobin glycated (A1C) >or=9% under maximal OAD combination therapy were enrolled. Previous therapies were discontinued, and patients were randomized into 2 groups. The combinations of IG and repaglinide were administered to group 1, and of IG and acarbose to group 2 for 13 weeks. Twenty patients in group 1 and 18 patients in group 2 completed the study. A1C levels were significantly decreased from 10.9+/-1.4% to 7.7+/-1.1% in group 1 and 11.0+/-1.4% to 8.1+/-1.4% in group 2. FBG levels were significantly decreased from 11.9+/-2.7 to 7.1+/-2.3 mmol/l in group 1 and 11.1+/-2.5 to 6.8+/-1.4 mmol/l in group 2. Post-prandial glucose levels were significantly decreased from 15.3+/-3.8 to 10.3+/-3.0 mmol/l in group 1 and 14.0+/-3.1 to 8.9+/-2.2 mmol/l in group 2. Intergroup comparisons indicated no significant differences. More weight gain was detected in group 1, compared to the baseline. Symptomatic hypoglycemia incidence was similar in both groups. Severe hypoglycemic attacks were seen in two patients in group 1. Flatulence incidence was higher in acarbose group. Conclusively, repaglinide and acarbose were equally effective when combined with IG for obese Type 2 diabetic patients controlled inadequately with OAD alone. Furthermore, acarbose seems to have advantages over repaglinide concerning weight gain and severe hypoglycemic attacks.

Topics: Acarbose; Blood Glucose; Carbamates; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity; Piperidines; Weight Gain

Insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) and multiple daily injections (MDIs) with insulin glargine as basal insulin and mealtime insulin lispro have not been prospectively compared in people naïve to either regimen in a multicenter study. We aimed to help close that deficiency.. People with type 1 diabetes on NPH-based insulin therapy were randomized to CSII or glargine-based MDI (both otherwise using lispro) and followed for 24 weeks in an equivalence design. Fifty people were correctly randomized, and 43 completed the study.. Total insulin requirement (mean +/- SD) at end point was 36.2 +/- 11.5 units/day on CSII and 42.6 +/- 15.5 units/day on MDI. Mean A1C fell similarly in the two groups (CSII -0.7 +/- 0.7%; MDI -0.6 +/- 0.8%) with a baseline-adjusted difference of -0.1% (95% CI -0.5 to 0.3). Similarly, fasting blood glucose and other preprandial, postprandial, and nighttime self-monitored plasma glucose levels did not differ between the regimens, nor did measures of plasma glucose variability. On CSII, 1,152 hypoglycemia events were recorded by 23 of 28 participants (82%) and 1,022 in the MDI group by 27 of 29 patients (93%) (all hypoglycemia differences were nonsignificant). Treatment satisfaction score increased more with CSII; however, the change in score was similar for the groups. Costs were approximately 3.9 times higher for CSII.. In unselected people with type 1 diabetes naïve to CSII or insulin glargine, glycemic control is no better with the more expensive CSII therapy compared with glargine-based MDI therapy.

Topics: Adult; Age of Onset; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin Lispro; Insulin, Long-Acting; Kinetics; Male; Middle Aged

Intravenous insulin improves clinical outcome in patients hospitalized in intensive care units. Whether glucose control with multiple daily subcutaneous insulin injections (MDI) is beneficial in patients hospitalized in general medical wards is unknown. We tested the feasibility, safety and efficacy of glucose control with MDI in diabetic patients hospitalized in a general medicine ward.. Eighty-eight adults with diabetes mellitus were studied in an internal medicine department. All patients were treated with subcutaneous pre-meal insulin analogue and Glargin insulin. A conservative and an intensified protocol was tested.. Mean daily glucose levels decreased in the conservatively treated patients from 275+/-71 mg/dl at day 1 to 197.0+/-60 mg/dl at day 4 of hospitalization p=0.0001 and in the intensified protocol to 191+/-38 mg/dl already on day 1 remaining stable throughout the hospitalization. A mean daily glucose <180 mg% was reached by day 2 in 48% of patients in the intensified and in 32% in the conservative groups. Only one serious event of hypoglycemia was noted in the intensified group.. Intensive insulin treatment with MDI is feasible, safe and efficacious in general medicine wards.

Topics: Aged; Algorithms; Blood Glucose; Diabetes Mellitus, Type 1; Fasting; Feasibility Studies; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Internal Medicine; Male; Middle Aged; Postprandial Period

This long-term study was designed to further characterise the retinal safety profile of insulin glargine and human neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus.. An open-label, 5 year, randomised (1:1), multicentre, stratified, parallel-group study conducted in the USA and Canada enrolled individuals with type 2 diabetes and either no or non-proliferative retinopathy (less than severe; Early Treatment Diabetic Retinopathy Study [ETDRS] level less than 53 in both eyes) who were treated with oral hypoglycaemic agents (OHAs) alone, insulin alone or OHAs with insulin for >/=3 months prior to study entry and a baseline HbA(1c) level of 6.0-12.0%. Patients were randomised by the investigator according to the centralised interactive voice response system to receive twice-daily NPH insulin (n = 509) or once-daily basal insulin glargine (n = 515). The investigator was not blinded to the treatment group to which each participant had been assigned. The main objective of this study was to compare the progression of diabetic retinopathy between treatment groups by analysing the percentage of patients with three or more step progression in the ETDRS retinopathy patient-level severity scale after treatment with either basal insulin. Masked, centralised grading of seven-field stereoscopic fundus photographs was used.. Similarly sustained glycaemic control was observed in both the insulin glargine and NPH insulin treatment groups. Despite a slightly greater severity of diabetic retinopathy for the insulin glargine group at baseline, three or more step progression in ETDRS score from baseline to end-of-study was similar between treatment groups (14.2% [53/374] of insulin glargine-treated patients vs 15.7% [57/363] of NPH-treated patients); the difference in the incidence of progression was -1.98% (95% CI -7.02, 3.06%). Other measures of retinopathy-the development of proliferative diabetic retinopathy and progression to clinically significant macular oedema-occurred to a similar degree in both treatment groups. No other safety issues, such as unexpected adverse events for either insulin emerged during the 5 year study. However, NPH insulin treatment was associated with a higher incidence of severe hypoglycaemia compared with insulin glargine.. This study shows no evidence of a greater risk of the development or progression of diabetic retinopathy with insulin glargine vs NPH insulin treatment in patients with type 2 diabetes mellitus.. ClinicalTrials.gov NCT00174824. This study was sponsored by sanofi-aventis.

Topics: Aged; Blood Glucose; Canada; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Internationality; Male; Middle Aged; Patient Selection; United States

This treat-to-target study compared the efficacy and safety of insulin detemir (IDet) and insulin glargine (IGla) in a basal-bolus (insulin aspart) regimen in type 2 diabetes.. 385 patients were randomized 2 : 1 (IDet : IGla). Non-inferiority of IDet to IGla was determined by HbA(1c) 95% CI upper limit <0.4.. IDet and IGla showed similar efficacy in HbA(1c) reduction at 26 weeks, as the non-inferiority criterion was met at 26 weeks (LS mean [Det-Gla]: 0.207; 95% CI: 0.0149,0.3995). It appeared that IGla in some cases did better than IDet in terms of HbA(1c), but the difference (0.207%) was not clinically meaningful. Based on the CONSORT guideline, non-inferiority analysis using the LOCF approach was inconclusive regarding possible inferiority of delta 0.4 (LS mean of [Det-Gla]: 0.307; 95% CI: 0.1023, 0.5109). HbA(1c) decreased significantly from baseline in IDet (-1.1% [26 weeks], -0.9% [LOCF], p < 0.001) and in IGla (-1.3% [26 weeks, LOCF], p < 0.001). Final HbA(1c) were 7.1% (26 weeks) and 7.3% (LOCF) in IDet, and 6.9% (26 weeks) and 7.0% (LOCF) in IGla. Final FPG were 130 mg/dL (26 weeks) and 135 mg/dL (LOCF) in IDet, and 134 mg/dL (26 weeks) and 137 mg/dL (LOCF) in IGla. There was significantly less weight gain in IDet-treated patients (1.2 +/- 3.96 kg versus 2.7 +/- 3.94 kg, p = 0.001). Hypoglycemia risk was comparable between groups. The majority of IDet-treated patients (87.4%) remained on a once-daily basal insulin regimen throughout the study.. IDet and IGla were both effective and safe treatments for glycemic control in a basal-bolus regimen for type 2 diabetes. Clinically significant reductions in HbA(1c) were achieved in both groups, but with significantly less weight gain in the IDet group at comparable basal insulin dosage.

Topics: Adult; Blood Glucose; Body Mass Index; Confidence Intervals; Diabetes Mellitus, Type 2; Edema; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Poisson Distribution; Respiratory Tract Infections; Time Factors; Treatment Outcome; Weight Gain

Patients with type 1 diabetes require intensive insulin therapy for optimal glycemic control. AIR((R)) inhaled insulin (system from Eli Lilly and Company, Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) may be an efficacious and safe alternative to subcutaneously injected (SC) mealtime insulin.. This was a Phase 3, 2-year, randomized, open-label, active-comparator, parallel-group study in 385 patients with type 1 diabetes who were randomly assigned to receive AIR insulin or SC insulin (regular human insulin or insulin lispro) at mealtimes. Both groups received insulin glargine once daily. Efficacy measures included mean change in hemoglobin A1C (A1C) from baseline to end point, eight-point self-monitored blood glucose profiles, and insulin dosage. Safety assessments included hypoglycemic events, pulmonary function tests, adverse events, and insulin antibody levels.. In both treatment groups, only 20% of subjects reached the target of A1C <7.0%. A significant A1C difference of 0.44% was seen favoring SC insulin, with no difference between the groups in insulin doses or hypoglycemic events at end point. Patients in both treatment groups experienced progressive decreases in lung function, but larger (reversible) decrements in diffusing capacity of the lung for carbon monoxide (DL(CO)) were associated with AIR insulin treatment. Greater weight gain was seen with SC insulin treatment.. The AIR inhaled insulin program was terminated by the sponsor prior to availability of any Phase 3 data for reasons unrelated to safety or efficacy. Despite early termination, this trial provides evidence that AIR insulin was less efficacious in lowering A1C and was associated with a greater decrease in DL(CO) and increased incidence of cough than SC insulin in patients with type 1 diabetes.

Topics: Administration, Inhalation; Adult; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 1; Female; Forced Expiratory Volume; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Safety; Vital Capacity

Patients with type 2 diabetes often initiate insulin with once-daily basal insulin. Over time, many patients intensify their insulin regimens in an attempt to attain and sustain glycemic targets. This study compares three intensification approaches: changing insulin glargine to preprandial AIR inhaled insulin (developed by Alkermes, Inc. [Cambridge, MA] and Eli Lilly and Company [Indianapolis, IN]; AIR is a registered trademark of Alkermes, Inc.), intensifying glargine via validated titration algorithms (IG), or adding AIR insulin while intensifying glargine (AIR + IG).. Five hundred sixty patients with hemoglobin A(1c) (A1C) of 7.5-10.5%, on one or more antihyperglycemic medications, and on once-daily insulin glargine for > or =4 months were randomly allocated to one of the three treatments lasting 52 weeks. The primary objective assessed between-group differences in A1C mean change from baseline to 24 weeks using last-observation-carried-forward (LOCF) in the intent-to-treat population.. At 24 weeks, A1C was reduced from a mean baseline of 8.5% to 7.7%, 7.9%, and 7.5% for the AIR, IG, and AIR + IG groups, respectively. AIR produced 0.20% greater A1C decrease than IG (least-squares mean difference = -0.20%; 95% confidence interval [CI], -0.39, -0.02). AIR + IG had a 0.35% greater A1C decrease versus IG (95% CI, -0.57, -0.13). The -0.15% difference between AIR + IG versus AIR was not significant (P < 0.198). More hypoglycemia categorized as severe occurred with AIR alone versus IG alone at LOCF end points. More nocturnal hypoglycemia occurred with IG alone versus AIR alone and AIR + IG.. Preprandial inhaled insulin provides an alternative for patients not optimized on insulin glargine alone. Glycemic control, hypoglycemic risk, delivery preference, and regimen complexity must be considered when selecting insulin initiation and optimization regimens.

Topics: Administration, Inhalation; Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Least-Squares Analysis; Male; Middle Aged

To assess the efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine, administered once daily in subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs.. In this 26-week, open-labeled, randomized, parallel-group, multinational, treat-to-target trial, 480 insulin-naïve subjects were randomized to receive either BIAsp 30 before dinner or insulin glargine at bedtime, both in combination with metformin and glimepiride.. NCT00469092, ClinicalTrials.gov.. A total of 433 subjects completed the trial. Estimated mean reduction in HbA(1c) from baseline to end of treatment was -1.41% with BIAsp 30 and -1.25% with insulin glargine (BIAsp 30 - insulin glargine = -0.16%, 95% CI [-0.30; -0.02], p = 0.029). At the end of treatment, mean HbA(1c) was 7.1% and 7.3% for BIAsp 30 and insulin glargine, respectively. Significantly lower plasma glucose levels were observed with BIAsp 30 post-dinner (BIAsp 30 - insulin glargine = -0.52 mmol/L, 95% CI [-1.02; -0.03], p = 0.04) and at bedtime (BIAsp 30 - insulin glargine = -0.78 mmol/L, 95% CI [-1.25; -0.31], p < 0.01). The relative risk (RR) of experiencing a nocturnal hypoglycemic episode (00:00-06.00 a.m.) was significantly higher with BIAsp 30 than with insulin glargine (1.1 versus 0.5 episodes/year, RR = 2.41, 95% CI [1.34; 4.34], p = 0.003), but overall hypoglycemia rates were low. There were three major hypoglycemic episodes in each group.. With respect to HbA(1c), BIAsp 30 fulfilled the statistical criteria for non-inferiority and superiority to insulin glargine and, according to pre-defined criteria, the improvements in HbA(1c) are considered clinically equivalent. Subjects had an increased risk of minor nocturnal hypoglycemia with BIAsp 30. There were no differences in treatment satisfaction between the two groups.

Topics: Administration, Oral; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Dosage Forms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Failure

To evaluate prospectively the efficacy and safety of insulin glargine use for the metabolic control of type 1 diabetes mellitus (T1DM) children younger than eight years old.. Nineteen boys and 11 girls with T1DM were included. Before initiating insulin glargine, all children received intensive NPH and aspart insulins for three months. Afterwards, they were assisted for 12 more months for glargine treatment. All patients performed self blood glucose monitoring before and two hours after meals and in early morning (3:00 AM). Primary endpoints: metabolic control using A1C levels; frequency of mild hypoglycemia (capillary glycemia < 60 mg/dL); and frequency of severe hypoglycemia (loss or alteration of consciousness, seizures or need for medical intervention).. Mean A1C at the study entry was 8.68% and after 12 months of glargine, was 8.64% (p = 0.82). Frequency of mild hypoglycemia at 3.00 AM was 1.43/3 months during the NPH period and 0.28/3 months during the glargine period (p < 0.007). Frequency of severe hypoglycemia was 0.56/3 months during the NPH period and 0.008/3 months during the glargine period (p < 0.002).. The treatment of T1DM children with insulin glargine was considered as efficacious as with NPH. However, a better safety profile, disclosed by the lower incidence of nocturnal and severe hypoglycemia episodes, was observed for insulin glargine.

Topics: Analysis of Variance; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome

The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type 1 diabetes mellitus (T1DM).. This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged > or = 18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA1c) value < or = 11.0% at screening. Patients were randomized in a 2:1 ratio to receive either detemir or glargine for 52 weeks. The basal insulin was initially administered once daily (in the evening) in both groups; if patients in the detemir group were achieving the plasma glucose (PG) target before breakfast but not before dinner, they were switched to twice-daily administration. Glargine was administered once daily throughout the trial, according to its approved labeling. Each patient attended 13 study visits and received 16 scheduled telephone calls from the trial site. The primary efficacy end point was glycemic control (HbA1c) after 52 weeks of treatment. Secondary end points included the number of patients achieving an HbA1c value < or = 7.0%, with or without a major hypoglycemic episode in the last month of treatment; fasting PG (FPG); within-patient variation in self-monitored plasma glucose (SMPG) before breakfast and dinner; and 10-point SMPG profiles. The noninferiority margin was 0.4%, consistent with US Food and Drug Administration guidelines.. Four hundred forty-three patients (mean [SD] age, 42 [12] years; body mass index, 26.5 [4.0] kg/m2; duration of diabetes, 17.2 [11.4] years; HbA1c, 8.1% [1.1%]) received study treatment. After 52 weeks, the estimated mean HbA1c did not differ significantly between the detemir and glargine groups (7.57% and 7.56%, respectively; mean difference, 0.01%; 95% CI, -0.13 to 0.16), consistent with the noninferiority of detemir to glargine. The corresponding estimated changes in HbA1c were -0.53% and -0.54%. In the 90 patients who completed the trial on once-daily detemir and the 173 patients who completed the trial on twice-daily detemir, the estimated changes in HbA1c were -0.49% and -0.58%, respectively. After 52 weeks, there were no significant differences in the proportions of those receiving detemir and glargine who achieved an HbA1c value < or = 7.0% without major hypoglycemia (31.9% and 28.9%, respectively). In addition, there were no significant differences in estimated mean FPG (8.58 and 8.81 mmol/L; mean difference, -0.23 mmol/L; 95% CI, -1.04 to 0.58) or in basal insulin doses. The basal insulin dose was numerically higher in patients receiving detemir twice rather than once daily (0.47 vs 0.33 U/kg, respectively). The relative risks for total and nocturnal hypoglycemia with detemir versus glargine were 0.94 and 1.12, respectively (both, P = NS). Six patients (2.0%) randomized to the detemir group and 4 (2.7%) randomized to the glargine group withdrew due to adverse events.. During 52 weeks of basal-bolus therapy in patients with T1DM, detemir was noninferior to glargine in terms of overall glycemic control (HbA1c). When used according to the approved labeling, detemir and glargine did not differ in tolerability or in terms of the occurrence of hypoglycemia.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Double-Blind Method; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Sample Size; Treatment Outcome

To compare starter insulins in the elderly subgroup of the DURABLE trial 24-week initiation phase.. In a post-hoc analysis of the > or = 65 years subgroup enrolled in the DURABLE trial, we compared the safety and efficacy of lispro mix 25 (LM25: lispro 25%/insulin lispro protamine suspension 75%), n = 258, vs. glargine, n = 222, added to oral glucose-lowering agents.. Baseline glycated hemoglobin (HbA(1c)) was similar (LM25 8.7 +/- 1.2, glargine 8.8 +/- 1.1%, P = 0.612). At 24-weeks, LM25 patients had lower HbA(1c) (7.0 +/- 0.9 vs. 7.3 +/- 0.9%, P < 0.001), greater HbA(1c) reduction (-1.7 +/- 1.2 vs. -1.5 +/- 1.1%, P < 0.001), and more patients reaching HbA(1c) < 7.0% (55.6 vs. 41.0%, P = 0.005). LM25 patients were on more insulin (0.40 +/- 0.19 vs. 0.33 +/- 0.19 u/kg/day, P < 0.001) and experienced more weight gain (3.6 +/- 3.6 vs. 1.8 +/- 3.2 kg, P < 0.001). Additionally, LM25-treated patients reported a higher mean overall hypoglycaemia rate than glargine patients (40.8 +/- 47.6 vs. 31.1 +/- 48.5 episodes/patient/year, P = 0.037), while nocturnal hypoglycaemia rates were similar. Over 24 weeks, incidence of severe hypoglycaemia was higher for LM25 (4.3% vs. 0.9%, P = 0.018); however, by 24-week endpoint incidence was similar (0.8% vs. 0.0%P = 0.125).. In this elderly subgroup post-hoc analysis, LM25 demonstrated a lower endpoint HbA(1c) and a higher % of patients reaching HbA(1c) target of < 7.0%, but with more weight gain and higher rates of hypoglycaemia compared to glargine.

Topics: Administration, Oral; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Treatment Outcome; Weight Gain

We hypothesized that school nurse supervision of glucose and insulin-dose adjustment significantly improves the hemoglobinA(1c) (HbA(1c)) level in pediatric patients with poorly controlled type 1 diabetes mellitus (HbA(1c) > or = 9%). A total of 36 subjects were enrolled and 18 subjects were randomized to receive the 3-month intervention. Their average HbA(1c) was lowered by 1.6%, suggesting that this intervention helps this difficult group of patients.

Topics: Blood Glucose; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Nurse's Role; School Nursing

Injection of long-acting insulin at bedtime is a common therapeutic approach for patients with type 2 diabetes that is poorly controlled with oral regimens. Neutral protamine lispro (NPL) insulin has demonstrated better glycemic control and similar incidence of hypoglycemic events than that of neutral protamine Hagedorn insulin.. To compare the clinical efficacy and safety of bedtime NPL insulin or insulin glargine in patients with type 2 diabetes who had suboptimal glycemic control while receiving stable doses of metformin and sulfonylurea.. Open-label, randomized trial.. Teaching hospital (Azienda Ospedaliera Universitaria, Second University of Naples), Naples, Italy.. 116 adults receiving stable doses of metformin plus sulfonylurea for longer than 90 days with hemoglobin A(1c) (HbA(1c)) levels of 7.5% to 10% and fasting plasma glucose levels of 6.7 mmol/L or greater (> or =120 mg/dL).. 10 IU of NPL insulin or insulin glargine injected subcutaneously at bedtime with weekly dose titrations to target fasting glucose levels less than 5.6 mmol/L (<100 mg/dL) in addition to stable oral regimens. Patients receiving nighttime sulfonylurea before the study were switched to metformin.. The primary outcome was change in HbA(1c) levels from baseline to week 36. Secondary outcomes were HbA(1c) levels less than 7%, self-reported hypoglycemic episodes, insulin dose, self-monitored glucose level, and body weight. Twenty patients in each group had continuous glucose monitoring for 3 consecutive days before adding insulin and at week 36.. Improvement in HbA(1c) levels was similar in both groups (1.83% and 1.89% for NPL and glargine, respectively). The difference between the groups was 0.06 percentage point (95% CI, -0.1 to 0.15 percentage points). Secondary outcomes did not differ between groups. Hemoglobin A(1c) levels less than 7% occurred in 62% of patients receiving NPL and 64% of patients receiving glargine (difference, 2.0 percentage points [CI, -1.1 to 5.0 percentage points]). Fasting plasma glucose levels less than 5.6 mmol/L (<100 mg/dL) occurred in 40% of patients receiving NPL and 41% of patients receiving glargine (difference, 1.0 percentage point [CI, -0.9 to 3.0 percentage points]). Any hypoglycemic event occurred in 74% of patients receiving NPL and 67% of patients receiving glargine (difference, 7 percentage points [CI, -5 to 13 percentage points]). Continuous glucose level monitoring in the patients who had this measurement did not differ statistically.. The study was not blinded, had limited power to detect differences in hypoglycemic events, and did not obtain continuous glucose level monitoring for all patients.. Similar glycemic control occurred with the addition of NPL or glargine insulin to oral regimens in patients with poorly controlled type 2 diabetes. Hypoglycemia was similar in the 2 groups, but sample size limited the ability to make a definite safety assessment.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Protamines; Sulfonylurea Compounds; Weight Gain

This trial compared the efficacy and safety profiles of the insulin analogues detemir and glargine as the basal insulin component of a basal-bolus regimen in patients with type 2 diabetes mellitus (T2DM) who were being treated with oral antidiabetic drugs (OADs) or insulin with or without OADs.. This was a multinational, 52-week, openlabel, parallel-group, noninferiority, treat-to-target trial. Patients with a diagnosis of T2DM for > or = 12 months who had been receiving an OAD or insulin, with or without OADs, for > 4 months were randomized in a 2:1 ratio to receive detemir or glargine. According to the approved labeling, detemir could be administered once or twice daily, and glargine was administered once daily. Insulin aspart was given at mealtimes. Insulin secretagogues and a-glucosidase inhibitors were discontinued at study entry, and existing OADs were continued. Doses of detemir and glargine were titrated to achieve a prebreakfast (and predinner for detemir administered twice daily) plasma glucose target of < or = 6.0 mmol/L. Patients monitored their plasma glucose levels before breakfast and dinner on the 3 days before each of 13 scheduled visits, recorded their insulin doses on 1 of these 3 days, and recorded their 10-point self-monitored plasma glucose (SMPG) at baseline and after 24 and 52 weeks. The primary efficacy end point was glycosylated hemoglobin (HbA(1c)) at 52 weeks; secondary efficacy end points included changes in fasting plasma glucose (FPG), postprandial plasma glucose, insulin doses, and weight change at 52 weeks. Safety end points included the frequency of hypoglycemia and adverse events (AEs).. The intention-to-treat population included 319 patients (58.0% male, 42.0% female; 78.4% white; mean age, 58 years; mean weight, 92.8 kg; mean duration of diabetes, 13.6 years). At study entry, 46.1% of patients were receiving insulin and > or = 1 OAD, 35.4 were receiving insulin only, and 18.5% were receiving > or = 1 OAD only. At 52 weeks, there was no significant difference between detemir and glargine in terms of mean HbA(1c) (7.19% and 7.03%, respectively; mean difference, 0.17% [95% CI, -0.07 to 0.40]) or the mean decrease in HbAlc from baseline (-1.52% and -1.68%). The reduction in HbA(1c) was not significantly affected by whether detemir was administered once or twice daily. There were no significant differences between groups in terms of mean FPG (7.05 and 6.68 mmol/L) or the mean change in FPG from baseline (-2.56 and -2.92 mmol/L; mean difference, 0.36; 95% CI, -0.26 to 0.99). The overall shape of the 10-point SMPG profiles was not significantly different between groups. Mean weight gain at 52 weeks was significantly lower with detemir than with glargine (2.8 vs 3.8 kg; mean difference, -1.04; 95% CI, -2.08 to -0.01; P < 0.05). Doses of basal and prandial insulins at the end of the study were not significantly different between groups. Major hypoglycemic episodes were reported by 4.7% and 5.7% of patients in the respective treatment groups. There was no significant difference in the risk of hypoglycemia between groups. The proportion of patients with AEs and the number of AEs per patient were comparable between groups (185/214 patients [86.4%] reporting 743 AEs and 88/105 patients [83.8%] reporting 377 AEs).. when used as indicated as part of a basal-bolus regimen in patients with T2DM who had previously received other insulin and/or OAD regimens, detemir was noninferior to glargine in its effects on overall glycemic control. Both basal insulins were associated with clinically relevant reductions in hyperglycemia. Both were well tolerated, with no significant difference in the frequency of hypoglycemia or AEs.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; International Cooperation; Male; Middle Aged; Patients; Postprandial Period; Time Factors; Treatment Outcome

The AT.LANTUS trial recently demonstrated the efficacy and safety of insulin glargine initiation and maintenance using two different treatment algorithms in poorly controlled type 2 diabetes mellitus (T2DM). This sub-analysis investigated glycemic control and safety in 686 patients switching from premixed insulin (premix) with or without (+/-OADs) to once-daily glargine (+/-OADs/prandial insulin). A 24-week, multinational (n=59), multicenter (n=611), randomized study comparing two algorithms (Algorithm 1: clinic-driven titration; Algorithm 2: patient-driven titration) in four glargine+/-OADs treatment groups: alone, once- (OD), twice- (BD) or >twice- (>BD) daily prandial insulin. After switching to the glargine regimen, HbA(1c) levels significantly improved in the overall group (9.0+/-1.3 to 8.0+/-1.2%; p<0.001) and in all subgroups; fasting blood glucose levels also improved in all subgroups (overall: 167.1+/-50.0 to 106.9+/-27.2 mg/dL [9.3+/-2.8 to 5.9+/-1.5 mmol/L]; p<0.001). The incidence of severe hypoglycemia was also low in all four subgroups (< or =1.7%). Patients with T2DM switching from premix+/-OADs to glargine+/-OADs had significant reductions in glycemic control with a low incidence of severe hypoglycemia. The addition of prandial (OD, BD or >BD) insulin was associated with further improvements in glycemic control. These data provide support for the stepwise introduction of prandial insulin to a more physiologic basal-bolus regimen, which is under investigation.

Topics: Aged; Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

PREDICTIVE is a multi-national, prospective, observational study, assessing the safety and efficacy of insulin detemir in patients with diabetes.. The European cohort includes 20,531 patients with diabetes (7420 type 1) from 11 countries. A subgroup of 4782 type 1 patients were transferred from a basal-bolus regimen with NPH insulin (n = 3117) or insulin glargine (n = 1665) to insulin detemir basal-bolus therapy; or from a human insulin basal-bolus regimen (n = 570) to insulin detemir/insulin aspart (part of the pre-study NPH group). Mean follow-up was 14.4 weeks. The primary endpoint was serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary endpoints were: incidence of overall and nocturnal hypoglycaemia; haemoglobin A(1c) (HbA(1c)); fasting glucose; within-patient fasting glucose variability; and change in body weight.. SADRs were reported by 62 (2.0%) patients previously receiving NPH insulin, 45 (2.7%) patients previously receiving insulin glargine and seven (1.2%) patients previously receiving human basal-bolus insulins. Major hypoglycaemia was significantly reduced in NPH insulin (55%), insulin glargine (51%), and human basal-bolus insulin groups (54%; p < 0.0001 for all). Total and nocturnal hypoglycaemic episodes were also significantly reduced in all groups (p < 0.0001 for all). HbA(1c) was reduced in patients previously receiving NPH insulin (0.5%), insulin glargine (0.4%), and human basal-bolus insulins (0.6%; p < 0.0001 for all). Mean fasting glucose and within-patient fasting glucose variability significantly decreased in all patients (p < 0.0001 for all). Body weight remained stable.. In this open-label, prospective, observational study, insulin detemir basal-bolus therapy improved glycaemic control and reduced hypoglycaemia with weight neutrality in type 1 patients in actual clinical practice.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Body Weight; Diabetes Mellitus, Type 1; Drug-Related Side Effects and Adverse Reactions; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Prospective Studies; Treatment Outcome

Insulin glargine is difficult to use for children due to the number of injections required because it is claimed to be immiscible with rapid-acting insulin analogs. For this study, we hypothesized that treating new-onset type 1 diabetes with twice-daily insulin glargine plus a rapid-acting insulin analog mixed in the same syringe would result in better glycosylated hemoglobin than twice-daily neutral protamine Hagedorn with a rapid-acting insulin analog (standard treatment).. Forty-two patients with new-onset type 1 diabetes were started on standard treatment. Three months after diagnosis, if patients were found compliant and had a glycosylated hemoglobin level of < or = 9%, then they were randomly assigned either to receive insulin glargine twice daily mixed with a rapid-acting insulin analog or to continue on standard treatment for 3 more months. Additional lunchtime rapid-acting insulin analog injections were given for the insulin glargine group as necessary.. Nineteen patients in the insulin glargine group and 17 in the neutral protamine Hagedorn group completed the study. The glycosylated hemoglobin level at baseline was 6.8% +/- 1% vs 6.9% +/- 1% and at poststudy was 6.7% +/- 1.3% vs 7.6% +/- 1% in the insulin glargine versus neutral protamine Hagedorn group, respectively. Two patients in the insulin glargine group required lunch rapid-acting insulin analog in the last month of the study. Although both groups were encouraged to contact the principal investigator with all queries, more in the insulin glargine arm opted to do so.. Glycemic control with insulin glargine mixed with a rapid-acting insulin analog given twice daily seems significantly more effective than the standard therapy in newly diagnosed type 1 diabetes. Furthermore, it decreases pain and burden of injections for children with diabetes by allowing patients to mix glargine with rapid-acting insulin analog.

Topics: Adolescent; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Probability; Prospective Studies; Quality of Life; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome

For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs.. This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose < or =100 mg/dl (< or =5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A(1c) (HbA(1c)).. Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA(1c) decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (-1.4%, p < 0.001; algorithm 1 -1.3% vs. algorithm 2 -1.5%; p = 0.03) and glargine plus >1 OAD (-1.7%, p < 0.001; algorithm 1 -1.5% vs. algorithm 2 -1.8%; p = 0.001).. This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA(1c) with a low risk of hypoglycaemia. The greater reduction in HbA(1c) was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD.

Topics: Administration, Oral; Adult; Aged; Algorithms; Blood Glucose; Body Weight; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

This study investigated the effect of insulin glargine (LANTUS) versus NPH insulin on metabolic control and safety in Asian patients with Type 2 diabetes, inadequately controlled on oral hypoglycemic agents (OHAs).. In this open-label, randomized, parallel, multinational, 24-week, non-inferiority study, 443 patients received either once-daily insulin glargine (n=220) or NPH insulin (n=223) at bedtime, plus glimepiride (Amaryl).. Baseline characteristics were similar between the two groups. HbA(1c) levels decreased in the insulin glargine and NPH groups over the study period in the per-protocol (PP; -1.10% versus 0.92%) and full-analysis (FA; -0.99% versus -0.77%) populations. In the PP population, the difference between adjusted means (predefined equivalence region >-0.4%) was 0.19% (90% confidence interval [CI]: 0.02, 0.36), demonstrating non-inferiority between the two treatments. In a superiority analysis (FA population), the difference between adjusted mean changes in the two groups was 0.22% (95% CI: 0.02, 0.42), demonstrating the superiority of insulin glargine (p=0.0319). Moreover, the number of hypoglycemic episodes was significantly lower with insulin glargine versus NPH insulin (p<0.004), particularly severe (p<0.03) and nocturnal (p<0.001). Daily insulin dose increased from 9.6+/-1.5 to 32.1+/-17.6 U in the insulin glargine group and from 9.8+/-1.9 to 32.8+/-18.9 U in the NPH insulin group.. These results confirm earlier reports that insulin glargine provides superior glycemic control with less hypoglycemia and demonstrates that these benefits are consistent between different ethnicities.

Topics: Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sulfonylurea Compounds; Treatment Outcome

This study assessed the incidence of severe hypoglycaemia with two insulin glargine titration algorithms: Algorithm 1 (increments of at least 10%, but not exceeding 4U) versus Algorithm 2 (1-6U increments). In this multicenter (n=409), multinational (n=54), open-label, 24-week randomized trial in 2442 subjects with sub-optimally controlled Type 1 diabetes (T1DM), mean prior insulin therapy duration was 14.6+/-10.3 years. The incidence of severe hypoglycaemia was similar with Algorithms 1 and 2 (16.6events/100 patient-years versus 14.4events/100 patient-years). There were similar rates of both symptomatic and nocturnal hypoglycaemia. HbA(1c) and fasting blood glucose (FBG) decreased significantly (baseline to endpoint; p<0.001), and comparably with Algorithms 1 and 2 (HbA(1c): -0.64% versus -0.72%; FBG: -57mg/dL versus -59mg/dL). Mean basal insulin dose increased with both algorithms (+5.7U versus +5.9U). In a diverse population with longstanding T1DM, transfer from any insulin regimen, including basal-bolus or premixed insulin to an insulin glargine-based regimen resulted in significant improvements in glycaemic control, with low rates of severe hypoglycaemia, irrespective of the titration algorithm used.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

Successfully managing diabetes is a complex process that includes addressing issues of drug efficacy, safety and treatment satisfaction. Additionally, the combined impact of patient/disease characteristics and treatment outcomes on treatment satisfaction is not well understood. The purpose of this study was to examine the impact of age, weight, gender, co-morbid conditions, diabetes history, treatment burden, efficacy (HbA1c) and side effects (weight gain, hypoglycemic events) on patients' appraisal of treatment satisfaction using linear regression models.. Data from a multi-center, randomized clinical trial comparing the efficacy/safety of biphasic insulin aspart 70/30 (BIAsp 70/30) vs. glargine (Glar) among insulin naïve type 2 patients were analyzed. Subjects were between ages 18-75, with baseline HbA1c > 8% and BMI < or = 40 kg/m2 (N = 233). Treatment satisfaction was assessed by the Insulin Treatment Satisfaction Questionnaire (ITSQ).. When factors were examined independently, multiple significant relationships (age, co-morbidity, hypoglycemic events, and weight gain) with overall and/or domains of treatment satisfaction were found. However, when all significant relationships were examined together, only neuropathy, treatment efficacy, and number of hypoglycemic events maintained their previous significance.. By examining predictors independently, significant relationships were identified. However, not all findings remained significant when examined in combination with each other. Thus, to more accurately characterize the impact of factors on treatment satisfaction, a more comprehensive approach may be necessary. By improving patient treatment satisfaction, the efficacy of treatments, as well as critical treatment outcomes such as compliance and cost of care should be improved.

Topics: Adolescent; Adult; Age Factors; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Treatment Outcome; Weight Gain

To compare initiation of insulin therapy by adding once-daily insulin glargine to oral antidiabetic agents (OADs) with switching patients to premixed 30% regular, 70% human neutral protamine hagedorn insulin (70/30) without OADs.. A 24-week, multicenter, open, randomized (1:1), parallel study.. Three hundred sixty-four poorly controlled patients with type 2 diabetes mellitus were treated with once-daily morning insulin glargine with continued OADs (glimepiride+metformin) (glargine+OAD) or twice-daily 70/30 alone. Insulin dosage in each group was titrated to target fasting blood glucose (FBG) of 100 mg/dL or less (or=6.7 mmol/L) and hemoglobin (Hb)A(1c) levels between 7.5% and 10.5% on OADs (glargine+OAD, n=67; 70/30, n=63).. HbA(1c), FBG, hypoglycemia, insulin dose, and adverse events were recorded.. HbA(1c) decreased from baseline to endpoint for both glargine+OAD (from 8.8% to 7.0%) and 70/30 (from 8.9% to 7.4%); adjusted mean HbA(1c) decrease for glargine+OAD and 70/30 was -1.9% and -1.4%, respectively (P=.003). More patients reached HbA(1c) of 7.0% or less without confirmed nocturnal hypoglycemia with glargine+OAD (n=37, 55.2%) than with 70/30 (n=19, 30.2%) (P=.006). FBG decreased significantly more with glargine+OAD (-57 mg/dL (-3.2 mmol/L)) than with 70/30 (-40 mg/dL (-2.2 mmol/L)) (P=.002). Patients treated with glargine+OAD experienced fewer episodes of any hypoglycemia (3.68/patient-year) than did those treated with 70/30 (9.09/patient-year) (P=.008).. In elderly patients, addition of once-daily morning glargine+OAD is a simple regimen to initiate insulin therapy, restoring glycemic control more effectively and with less hypoglycemia than twice-daily 70/30 alone.

Topics: Administration, Oral; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Sulfonylurea Compounds; Weight Gain

To compare glycaemic control and risk of hypoglycaemia of twice-daily insulin detemir with once-daily insulin glargine in subjects with Type 1 diabetes.. In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either insulin detemir twice daily or insulin glargine once daily. each in combination with premeal insulin aspart.. After 26 weeks, HbA(1c) had decreased from 8.8 to 8.2% in the insulin detemir group and from 8.7 to 8.2% in the insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with insulin glargine than with insulin detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with insulin detemir than with insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with insulin detemir than with insulin glargine (P < 0.05). Body weight gain was not significantly different comparing insulin detemir and insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193).. Treatment with twice-daily insulin detemir or once-daily insulin glargine, each in combination with insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with insulin detemir.

Topics: Adolescent; Adult; Aged; Austria; Blood Glucose; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Risk Factors; South Africa; Treatment Outcome

The objective was to compare the impact on treatment satisfaction (TS) and quality of life (QoL) of early insulinization with glargine versus adjusting oral antidiabetic drug (OAD) therapy in people with Type 2 diabetes with uncontrolled glycemia. TS and QoL were assessed at baseline, weeks 12 and 24 within the Canadian INSIGHT, a randomized 24-week trial of Type 2 patients. A total of 366 patients randomized to either the insulin glargine arm (n=182) or the adjusted OAD therapy arm (n=184) completed both questionnaires. At baseline, TS and QoL were similar in both groups. A1c reduction was greater in the insulin glargine arm. TS improved from baseline in both treatment arms; however, there was greater increase with insulin glargine+OAD. Perceived frequency of hypoglycemia and hypoglycemia were lower at week 24, with no differences between the two groups. Perceived frequency of hyperglycemia improved with glargine at week 12, and no difference was found at 24 weeks. Finally, QoL improved in both groups, but significantly more with glargine at both weeks 12 and 24. Improving glucose control by adding insulin glargine to OAD therapy had a positive impact on TS and general QoL without complaints related to hypoglycemia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Quality of Life

To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-standing Type 1 diabetes (T1DM).. Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were randomized in a pilot 24-week prospective study to optimized analogue therapy (ANALOGUE; lispro/glargine); continuous subcutaneous insulin infusion therapy (CSII; lispro); or re-education with relaxation of blood glucose targets on existing conventional insulin regimen (EDUCATION). Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose.. Further severe hypoglycaemia was prevented in five participants (71%) in each group (P = 0.06). Incidence of severe hypoglycaemia was: 0.6 (ANALOGUE), 0.9 (CSII), and 3.7 (EDUCATION) episodes per patient year. Restoration of hypoglycaemia awareness was confirmed by validated questionnaire in three (43%) ANALOGUE, four (57%) CSII and five (71%) EDUCATION patients. Glycated haemoglobin (HbA1c) was significantly improved in the ANALOGUE group between weeks 0 and 24 (8.6 +/- 1.1 vs. 7.6 +/- 0.8%; P = 0.04 for change). Non-significant improvement was seen in the CSII group (8.5 +/- 1.9 vs. 7.4 +/- 1.0%; P = 0.06). No change in HbA1c was seen in the EDUCATION group (8.5 +/- 1.1 vs. 8.3 +/- 1.0%; P = 0.54). There were no episodes of diabetic ketoacidosis or any other adverse events in any group.. In this pilot randomized trial comparing optimized ANALOGUE, CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia, we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin Lispro; Insulin, Long-Acting; Male; Patient Education as Topic; Pilot Projects; Prospective Studies; Secondary Prevention

This study examined the impact of insulin glargine introduction in basal-bolus therapy in type 1 and type 2 diabetic patients with inadequate metabolic control (A1c > 6.9%) using previous NPH insulin regime. In this uncontrolled, retrospective study, 49 patients (28F/21M), average age 24.7 +/- 16.5, mean duration of DM 13.2 +/- 10.1 yrs., 93.1% DM1 patients, received insulin glargine plus mealtime rapid-acting insulin (lispro or aspart) followed by 90-day treatment. We analyzed mean total insulin dose, incidence of hypoglycemic events, convulsive crisis, hyperglycemic complications and A1c levels before and after three months of introduction of glargine therapy. A1c values were determined using the HPLC instrument, with a normal range of 4.3% to 6.9%. After switching to insulin glargine therapy, mean A1c dropped from 10.2 +/- 2.0 to 9.1 +/- 1.8%, with significant impact (p= 0.019). We observed a significant reduction of 0.11 U/kg/day in total insulin dose, dropped from 0.75 U/kg of NPH to 0.64 U/kg of glargine, with significant correlation (p< 0.05). The introduction of glargine therapy was coincident with a decrease of hypoglycemic crisis (p= 0.02), convulsive events due to hypoglycemia (severe hypoglycemic crisis) (p= 0.023) and ketosis (p= 0.001) switching MDI-treated patients with improvement of metabolic control (reduction of A1c levels). This therapy improved quality of life in these patients due to a significant reduction of hypoglycemic (including severe) events, ketosis episodes and total daily insulin dose, with important impact on health public services.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome

In this open study of clinical practice, 142 paediatric patients with type 1 diabetes mellitus (>1 year duration), stratified by age, received prandial insulin (regular or lispro) and either once daily insulin glargine (GLAR; n=74), titrated to target fasting blood glucose (FBG) levels 4.4-7.8 mmol/l, or NPH/semilente insulin (NPH insulin, administered once, twice or three times daily; n=68), titrated to target FBG 4.4-8.9 mmol/l. Both groups were treated for 20 +/- 10 months. HbA(1c) significantly increased in GLAR (7.3 +/- 1.0% to 7.6 +/- 1.1%; p = 0.003) and NPH/semilente insulin (7.7 +/- 1.6% to 8.3 +/- 1.5%; p = 0.0001) treated patients. The incidence of symptomatic hypoglycaemia was comparable between GLAR versus NPH/semilente insulin at endpoint (2.19 vs. 1.94 episodes/week); however, the overall incidence of severe hypoglycaemia was significantly lower with GLAR versus NPH/semilente insulin (0.14 vs. 0.73 events/patient-year; p = 0.002). The daily insulin dose was similar between the treatment groups; however, perceived quality of life (QoL) was better with GLAR. GLAR is associated with equivalent glycaemic control, less severe hypoglycaemia and improved QoL compared with NPH/semilente insulin.

Topics: Adolescent; Adult; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Hemoglobins; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Quality of Life

Unsatisfactory basal insulin substitution may lead to asymptomatic hypoglycemia in children and adolescents with type 1 diabetes (T1D). To investigate the effects of multiple daily injections before and after changing to insulin glargine (IG), continuous glucose monitoring system (CGMS) data were used to analyze glycemic control and hypoglycemic episodes during the two different therapy regimens.. Basal insulin therapy was changed to one daily injection of IG in 30 pediatric patients with T1D (14 boys and 16 girls; age 4.5-18.3 yr, median 14.2 yr; diabetes duration 0.5-15.6 yr, median 4.6 yr) having elevated fasting glucose or recurrent hypoglycemia despite treatment with multiple injection therapy (basal insulin: two to four injections of neutral protamine Hagedorn (NPH) and/or zinc lente insulin). Ambulatory CGMS was applied before and 6-8 wk after treatment change. Frequency of hypoglycemic and hyperglycemic episodes, glucose area under the curve (AUC), and time below 60 mg/dL and above 180 mg/dL, respectively, were calculated from CGMS data during the day (8:00-22:00 hours) and at night (22:00-8:00 hours).. Nocturnal hypoglycemia was detected by CGMS in 20 patients before and in 12 patients after the change to IG (p = .039), whereas both, the number of nocturnal and diurnal hypoglycemic episodes, decreased not significantly from 41 to 36 (p = .758) and 48 to 28 (p = .055), respectively. AUC and time below 60 mg/dL as well as hemoglobin A1c (HbA1c) were not significantly different before and after the change to IG.. Under treatment with IG, asymptomatic hypoglycemia was reduced without increase of HbA1c.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Monitoring, Ambulatory

Type 2 diabetes patients insufficiently controlled with sulfonylurea (SU) are commonly treated by switching to twice-daily premix insulin replacing SU. The efficacy of glargine (GL) added on to SU compared with the premix therapy has not been analyzed in Japan.. The open-label two-arm study was conducted in 30 type 2 diabetes patients poorly controlled [hemoglobin A(1c) (HbA(1c)) >7.5%] with SU with or without other oral hypoglycemic agents (OHAs). The GL group injected once-daily GL in addition to the OHAs. The aspart 70/30 (70/30) group discontinued SU among the OHAs and injected twice-daily 70/30. Patients were recommended either method in a block random method, and if twice-daily 70/30 was rejected, once-daily GL was selected only at the first time. The insulin dose was titrated to achieve a target fasting plasma glucose of <120 mg/dL and/or HbA(1c) of <7%.. Nineteen of 20 patients treated with GL and 11 of 14 patients treated with 70/30 completed the 6-month study. Mean HbA(1c) improved from 8.45% to 7.5% in the GL group and from 9.13% to 7.93% in the 70/30 group. The mean HbA(1c) decrease during 6 months was -0.95% in the GL group and -1.20% in the 70/30 group (P = 0.49). Mean insulin doses at 6 months were 12.0 units/day for the GL group and 26.7 units/day for the 70/30 group. Both therapies were well tolerated without severe hypoglycemia.. Once-daily GL injection added on to OHAs was equally safe and effective compared with twice-daily injection of aspart 70/30 premix replacing SU in type 2 patients insufficiently controlled with OHAs.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Sulfonylurea Compounds

To assess the effects of a structured in-patient diabetes training programme in people with Type 2 diabetes mellitus on a basal-bolus regimen using insulin glargine or NPH insulin and rapid-acting insulin analogues with respect to glycaemic control, weight development and incidence of hypoglycaemia in an outpatient-clinic setting.. This was a prospective, non-randomized, single centre, comparative observational study including 119 subjects. Pre-study treatment was a basal-bolus regimen with NPH insulin and a rapid-acting insulin analogue. Subjects either continued with NPH insulin (n=56) or were switched over to insulin glargine (n=63) at the discretion of the investigator (aiming at equal numbers in each group). Patients then attended routine out-patient follow up visits for 18 months.. HbA1c in the insulin glargine group improved statistically significant by -0.49%; [95%CI, -0.26, -0.71; p<0.001; HbA1c at endpoint 6.95+/-0.71%], whereas in the NPH group the reduction by -0.12% [95%CI, -0.31, 0.06; p=0.189; HbA1c at endpoint 7.22+/-0.74%] was statistically not significant. After 18 months of treatment the difference between treatment groups was 0.37% (p<0.015). Mean weight gain was significantly higher in the NPH group than in the glargine group (2.1 vs. 0.25 kg; p=0.025). A lower risk of hypoglycaemia in the glargine group (0.50 vs. 0.71 episodes/patient/month) did not reach statistical significance (p=0.081).. Following a structured in-patient diabetes training programme glycaemic control in people with Type 2 diabetes mellitus on a basal-bolus regimen improved significantly only with insulin glargine suggesting that training alone may not be sufficient to further improve metabolic control in relatively well controlled patients on NPH insulin. Therefore, in addition to a structured training programme also the insulin regimen should be optimized, e.g. by introduction of an insulin analogue.

Topics: Adult; Aged; Ambulatory Care Facilities; Body Weight; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Education as Topic; Prospective Studies

The primary objective of this study was to investigate the difference in the proportion of patients with conventionally detected hypoglycemia compared with continuous glucose monitoring system (CGMS, Medtronic MiniMed, Sylmar, CA)-detected glucose values < or = 60 mg/dL (< or = 3.3 mmol/L), during the 72-h CGMS measurement period after 8 weeks' treatment with insulin glargine.. This was a multicenter (n = 125), open-label, single-arm study in patients with Type 2 diabetes mellitus (T2DM) on multiple daily injections. Patients received NPH insulin (2-week run-in) followed by glargine (8-week treatment phase). Glucose levels were measured by CGMS and self-monitored blood glucose (SMBG) profiles over the 72-h pre- and post-treatment phase.. The full analysis set contained 367 patients [male 59%; mean age 59.2 years; mean body mass index 31.7 kg/m(2); mean hemoglobin A1c (HbA1c) 6.9%]. At end point, 209 patients (56.9%) experienced hypoglycemia according to CGMS; 97 (26.4%) recorded hypoglycemia by conventional methods. CGMS- and SMBG-determined mean daytime glucose levels were similar at baseline and end point; however, nocturnal glucose levels were significantly lower with CGMS versus SMBG at baseline [130.2 vs. 145.0 mg/dL (7.2 vs. 8.1 mmol/L)] and at end point [123.3 vs. 137.3 mg/dL (6.8 vs. 7.6 mmol/L)]. Glucose levels measured by CGMS and SMBG decreased, and HbA1c levels decreased from 6.90% at screening to 6.67% at end point (P < 0.001).. This study demonstrates that CGMS can be successfully employed in large clinical trial settings in patients with T2DM. This easy-to-implement method may provide additional insights into glucose levels and valuable information regarding the time patients spend within the preferred glucose range.

Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Time Factors

Addition of the long-acting basal human insulin analogue insulin glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic control on oral antidiabetic drugs (OADs) alone has previously been evaluated as effective, safe and convenient. This pilot study aimed to establish whether insulin glargine plus OADs is effective in Type 2 diabetes patients previously poorly controlled on premixed insulin therapy.. In an open, controlled, randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age 65.6+/-9.2 years; diabetes duration 15.3+/-7.6 years; insulin therapy duration 4.2+/-1.7 years, body mass index 31.4+/-2.9 kg/m2) with Type 2 diabetes (HbA1c>or=8.0%) on premixed human insulin (75/25 or 70/30) were randomized to once-daily morning insulin glargine plus glimepiride (Group A; n=17), insulin glargine plus glimepiride and metformin (Group B; n=18) or premixed insulin (Group C; n=17). Glycaemic control and incidence of hypoglycaemia were evaluated.. HbA1c decreased significantly from baseline in Groups A and B, but not in Group C; (Group A: 7.87+/-0.66%, -0.35%, p=0.013; Group B: 7.44+/-0.92%, -0.69%, p=0.0057; Group C: 7.83+/-1.13%, -0.25%, p=0.32). There were no between-treatment differences at endpoint in HbA1c, fasting blood glucose, mean daily blood glucose or symptomatic hypoglycaemia (mean events/patient: Group A, 2.2; Group B, 2.3; Group C, 2.0). At endpoint, 88% of patients in Group A, 81% in Group B and 94% in Group C opted to continue with their assigned regimen.. This pilot study is the first prospective study to show that switching from premixed insulin to insulin glargine plus OAD treatment resulted in similar glycaemic control and treatment satisfaction. The results support the need for prospective examination in a larger-scale clinical study in patients with long-standing Type 2 diabetes and sub-optimal glycaemic control previously using a conventional premixed insulin regimen.

Topics: Administration, Oral; Aged; Blood Glucose; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Pilot Projects; Prospective Studies; Sulfonylurea Compounds; Time Factors

This study was conducted to compare the efficacy and safety profiles of exenatide and insulin glargine therapy in patients with type 2 diabetes who had not achieved glucose control with metformin or sulfonylurea monotherapy.. This multinational, randomized, open-label, crossover noninferiority study compared the efficacy of exenatide 10 pg BID and insulin glargine QD (titrated targeting a fasting serum glucose (FSG) level < or =5.6 mmol/L) in patients with type 2 diabetes treated with a single oral antidiabetic agent. The study included two 16-week treatment periods. The primary a priori outcome variable was the change in glycosylated hemoglobin (HbA(lc)). Secondary outcomes included the proportion of patients achieving the American Diabetes Association (ADA) target HbA(lc) of < or =7% and the European Association for the Study of Diabetes target of < or =6.5%, the change in FSG, end-point values and change in the 7-point self-monitored glucose profile, and change in body weight. Adverse events were assessed based on standard laboratory tests and patient reports.. One hundred thirty-eight patients were randomized to study treatment (52.9% female, 47.1% male; 79.7% white; mean [SEM] age, 54.9 [0.8] years; duration of diabetes, 7.4 [0.4] years; body mass index, 31.1 [0.4] kg/m(2); weight, 84.8 [1.4] kg) while continuing to receive metformin (55.1%) or a sulfonylurea (44.9%). The population had a baseline least squares (LS) mean (SEM) HbA(lc) of 8.95% (0.09%) and an LS mean FSG concentration of 12.0 (0.3) mmol/L. Both exenatide and titrated insulin glargine therapy were associated with similar significant changes from baseline in HbA(1c) (both, -1.36% [0.09%]; P < 0.001); the difference between groups was not statistically significant. The LS mean HbA(1c) at end point was above the ADA target with both treatments (exenatide, 7.57% [0.09%]; insulin glargine, 7.58% [0.09%]). Similar proportions of patients achieved an HbA(1c) < or =7% (37.5% and 39.8%, respectively; P = NS) or < or =6.5% (21.5% and 13.6%). Patients lost weight during exenatide treatment, whereas they gained weight during insulin glargine treatment; the between-group difference in weight change was statistically significant (LS mean difference, -2.2 [0.3] kg; 95% CI, -2.8 to-1.7; P < 0.001). Both exenatide and insulin glargine were associated with significant reductions from baseline in FSG (-2.9 [0.2] and -4.1 [0.2] mmol/L, respectively; both, P < 0.001), although the reduction was significantly greater with insulin glargine compared with exenatide (LS mean difference, 1.2 [0.3] mmol/L; 95% CI, 0.7 to 1.7; P < 0.001). Compared with insulin glargine, exenatide was associated with significantly lower 2-hour postprandial glucose (PPG) excursions (P < 0.016) and total daily mean glucose excursion (P < 0.001). The proportions of patients reporting nausea during exenatide and insulin glargine treatment were 42.6% and 3.1%, respectively; the proportions reporting vomiting were 9.6% and 3.1%. The incidence of hypoglycemia in the 2 groups was 14.7% and 25.2% (P = NS).. In this open-label, crossover study, treatment with exenatide or insulin glargine for 16 weeks was associated with similar significant improvements from baseline in HbA(1c), independent of treatment order. The improvements in HbA(1c) from baseline did not differ significantly between treatment groups. Exenatide therapy was associated with significant reductions in body weight and PPG excursions compared with insulin glargine, whereas insulin glargine was associated with a significantly greater reduction in FSG compared with exenatide. These findings provide additional information to guide treatment decisions in patients with type 2 diabetes who are potential candidates for either therapy.

Topics: Adult; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Resistance; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Peptides; Sulfonylurea Compounds; Venoms

To compare blood glucose control when insulin glargine is given at lunch-time, dinner-time, and bed-time in people with Type 1 diabetes using insulin lispro at meal-times.. In this 16-week, three-way, cross-over study, 23 people with Type 1 diabetes were randomized to insulin glargine injection at lunch-time (L) [mean 12.37 +/- 00.34 (+/- sd) h], dinner-time (D) (18.12 +/- 00.40 h), or bed-time (B) (22.29 +/- 00.40 h), each plus meal-time insulin lispro. Each 4-week treatment period concluded with a 24-h inpatient metabolic profile.. Insulin doses, HbA(1c), and fructosamine concentration did not differ between treatment periods. Pre-breakfast self-monitored blood glucose (SMBG) concentration was higher with injection of glargine at lunch-time than at other times [L: 9.2 +/- 0.3 (+/- se) vs. D: 8.2 +/- 0.3 or B: 8.0 +/- 0.3 mmol/l, P = 0.016], as probably was pre-lunch SMBG (L: 8.6 +/- 0.7 vs. D: 6.4 +/- 0.7 or B: 6.4 +/- 0.8 mmol/l, P = 0.051). Pre-dinner SMBG level was higher with dinner-time glargine than other injection times (D: 9.4 +/- 0.9 vs. L: 4.9 +/- 0.9 or B: 7.4 +/- 1.1 mmol/l, P = 0.007). For 22.00 to 02.00 h, mean inpatient plasma glucose concentration was higher with injection of glargine at bed-time than other times (B: 9.1 +/- 0.6 vs. L: 7.8 +/- 0.6 or D: 6.7 +/- 0.6 mmol/l, P = 0.023). Plasma free insulin concentration was lower at the end of the afternoon with dinner-time glargine than other injection times (D: 11.5 +/- 1.4 vs. L: 20.2 +/- 1.3 or B: 16.5 +/- 1.3 mU/l, P < 0.001). Frequency of hypoglycaemia was not different, but timing of hypoglycaemia differed between treatment periods.. Blood glucose levels rise around the time of injection of insulin glargine whether given at lunch-time, dinner-time or bed-time. Bed-time injection leads to hyperglycaemia in the early part of the night which is improved by giving insulin glargine at lunch-time or dinner-time.

Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Female; Fructose; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Time Factors

In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.. In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.. During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).. Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.

Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Lipid Metabolism; Liver; Male; Metformin; Middle Aged

To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen.. In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 +/- 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile.. HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference -0.5 (95% CI -0.7, -0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l(-1) h(-1), P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l(-1) h(-1), P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l(-1) h(-1), P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001).. Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia.

Topics: Adult; Area Under Curve; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

To determine whether mixing insulin glargine (IG) with a rapid-acting insulin (RAI) analogue in the same syringe had any deleterious effects on glycemic control in children with type 1 diabetes mellitus.. Data from 55 children mixing the IG with a RAI analogue was collected for 6 months before and 6 months after the insulin mixing began. Data from a control group of 55 children not mixing the insulins was collected at similar intervals. Parameters evaluated included hemoglobin A1c (HbA1c) values, number of non-severe and severe hypoglycemic events, number of diabetic ketoacidosis (DKA) events, and blood glucose distribution patterns.. After 6 months of study, HbA1c values were equivalent for the control and test groups (8.54+/-1.14 vs 8.61+/-1.14, respectively; P=1.0000). Percentages of blood glucose values in, above, and below the target range did not vary significantly in the groups. There were no significant differences in the groups in the occurrence of non-severe or severe hypoglycemic events or of DKA events.. There were no significant differences in glycemic control between children who mixed IG in the same syringe with a RAI analogue compared with children who took separate injections.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Combinations; Female; Humans; Hypoglycemia; Injections; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Matched-Pair Analysis; Patient Compliance; Prospective Studies; Regression Analysis

To compare the incidence of nocturnal hypoglycemia and glycemic control following bedtime or morning insulin glargine (LANTUS; glargine) plus glimepiride.. In this 24-week, multinational, open, randomized study, 624 patients with type 2 diabetes poorly controlled on oral therapy received morning or bedtime glargine plus morning glimepiride (2, 3 or 4 mg) titrated to a target fasting blood glucose level < or = 5.5 mmol/l.. The incidence of nocturnal hypoglycemia was equivalent between the two groups, with morning glargine non-inferior to bedtime (13.0 VS. 14.9 % of patients; between-treatment difference -1.9 %; one-sided 95 % confidence interval -100 %; 2.84 %). At endpoint, similar improvements in glycemic control were observed with morning compared to bedtime glargine: HbA1c: -1.65 +/- 1.21 VS. -1.57 +/- 1.16 %; p = 0.42; fasting blood glucose: -4.25 +/- 2.82 VS. -4.48 +/- 2.75 mmol/l; p = 0.08. The endpoint mean daily glargine dose was comparable (34.7 +/- 17.4 VS. 32.4 +/- 17.0 IU; p = 0.15), and there was no significant between-treatment difference in the change in body weight (2.1 VS. 1.8 kg; p = 0.39).. Once-daily glargine can be administered in a flexible morning or bedtime regimen (plus morning glimepiride) to achieve good glycemic control without any difference in hypoglycemia.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Sulfonylurea Compounds; Time Factors; Treatment Outcome

Type 2 diabetes (T2DM) patients often fail to achieve adequate glycemic control with oral antidiabetic drugs (OADs). Insulin has been shown to improve glycemic control in these patients but with increased risk of hypoglycemia. This study compared the efficacy and safety of insulin glargine and NPH insulin, both in combination with a once-daily fixed dose of glimepiride, in terms of glycemic control and incidence of hypoglycemia.. In this open-label, 24-week randomized trial in ten Latin American countries, T2DM patients poorly controlled on OADs (HbA1c > or = 7.5 and < or = 10.5%) received glimepiride plus insulin glargine (n = 231) or NPH insulin (n = 250) using a forced titration algorithm. The primary endpoint was the equivalence of 24-week mean changes in HbA1c.. Insulin glargine and NPH insulin achieved similar HbA1c reductions (adjusted mean difference -0.047; 90% CI -0.232, 0.138; per-protocol analysis). Confirmed nocturnal hypoglycemia was significantly lower with insulin glargine vs. NPH insulin (16.9 vs. 30.0%; p <0.01; safety analysis). Patients receiving insulin glargine were significantly more likely to achieve HbA1c levels < 7.0% without hypoglycemia (27 vs. 17%; p = 0.014; per-protocol analysis). There was a more pronounced treatment satisfaction improvement with insulin glargine vs. NPH insulin (p <0.02; full analysis). The proportion of patients who lost time from work or normal activities due to diabetes was lower with insulin glargine vs. NPH (1.8 vs. 3.3%; full analysis).. In patients with T2DM, inadequately controlled on OADs, once-daily insulin glargine plus glimepiride is effective in improving metabolic control with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sulfonylurea Compounds

In patients with type 2 diabetes, insulin therapy is commonly initiated with either a single dose of basal insulin or twice-daily premixed (basal plus prandial) insulin despite no widely accepted recommendation. We compared the glycaemic control, as measured by a change in HbA1c, of intensive mixture therapy (IMT), a basal plus prandial regimen using insulin lispro mixture 50/50 (50% lispro and 50% NPL) before breakfast and lunch and insulin lispro mixture 25/75 (25% lispro and 75% NPL) before dinner, vs. once-daily insulin glargine therapy, while continuing patients on oral antidiabetes medications.. Following inadequate glycaemic control (HbA1c 1.2-2.0 times the upper limit of normal) and at least 2 months of two or more oral antidiabetes agent therapy, 60 insulin-naïve patients with type 2 diabetes were randomized to one of the insulin regimens for 4 months with crossover to the alternative regimen for an additional 4 months. Glycaemic goals were preprandial blood glucose <120 mg/dl (6.7 mmol/l) and 2-h postprandial blood glucose <180 mg/dl (10.0 mmol/l). The insulin dose was optimized by investigators without forced titration.. Mean prestudy (baseline) HbA1c for all patients was 9.21 +/- 1.33% (+/-s.d.). IMT compared to glargine resulted in both a lower endpoint in HbA1c (7.08 +/- 0.11% vs. 7.34 +/- 0.11%; p = 0.003) and a greater change in HbA1c from pretherapy (-1.01 +/- 0.10% vs. -0.75 +/- 0.10%; p = 0.0068). Forty-four per cent of patients receiving IMT and 31% of patients receiving insulin glargine achieved HbA1c < or = 7%. Two-hour postprandial glucose values (for all three meals) and predinner glucose values were significantly less with IMT than with insulin glargine (p = 0.0034, 0.0001, 0.0066 and 0.0205). Overall hypoglycaemia throughout the complete treatment period was infrequent (IMT vs. Glargine: 3.98 +/- 4.74 vs. 2.57 +/- 3.22 episodes/patient/30 days, p = 0.0013), and no severe hypoglycaemia was observed during the study with either therapy. There was no difference in nocturnal hypoglycaemia between the two therapies. The mean insulin dose at the end of therapy was greater for IMT than for once-daily insulin glargine (0.353 +/- 0.256 vs. 0.276 +/- 0.207 IU/kg, p = 0.0107).. In combination with oral antidiabetes agents, multiple daily injections of a basal plus prandial insulin IMT regimen (using premixed insulin lispro formulations) resulted in greater improvements and a lower endpoint in HbA1c compared with a basal-only insulin regimen. IMT also resulted in improved postprandial blood glucose control at each meal and enabled administration of a greater daily dose of insulin, which most likely contributed to these lower HbA1c measures. This greater reduction in HbA1c with IMT is accompanied by a small increased occurrence of mild hypoglycaemia but without any severe hypoglycaemia. Greater consideration should be given to initiating insulin as a basal plus prandial regimen rather than a basal-only regimen.

Topics: Adult; Aged; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

Insulin is generally withheld until people with Type 2 diabetes are unresponsive to other therapies. However, its potential advantages suggest that it could be added earlier to achieve glycaemic goals; this possibility was tested in a clinical trial.. Consenting adults aged 18-80 years with Type 2 diabetes for at least 6 months, HbA1c of 7.5-11%, and on 0, 1 or 2 oral agents, were randomized to one of two therapeutic approaches for 24 weeks: evening insulin glargine plus self-titration by 1 unit/day if the fasting plasma glucose (FPG) was > 5.5 mmol/l; or conventional therapy with physician adjustment of oral glucose-lowering agents if capillary FPG levels were > 5.5 mmol/l. The primary outcome was the first achievement of two consecutive HbA1c levels

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Canada; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Treatment Outcome

Topics: Adult; Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Incidence; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Self Administration; Self Care

Traditionally hyperglycemia in surgical inpatients has been managed with six-hourly sliding-scale regular insulin. However, this approach is usually ineffective in preventing hyperglycemia since no basal insulin is provided. We compared glycemic control using NPH and regular insulin versus glargine insulin alone in patients after cardiovascular surgery on a general surgical ward.. Ninety-four hyperglycemic patients were randomized to subcutaneous insulin using twice-daily NPH/regular or once-daily glargine if they required at least 1 unit/h of intravenous insulin at the time of transfer from the ICU. NPH/regular was adjusted twice daily; glargine was adjusted once daily. Blood glucose was measured four times daily and targeted to 80-140 mg/dL.. The mean blood glucose after NPH/regular (124 mg/dL) and glargine (131 mg/dL) was similar (P = 0.065). In the subgroup of patients with a history of diabetes, mean blood glucose was significantly lower after NPH/regular (133 mg/dL) versus glargine (154 mg/dL) (P = 0.016). Blood glucose less than 60 mg/dL was significantly less common after glargine (0.5%) as compared with NPH/regular (2%) (P = 0.036).. Once-daily glargine insulin provides good glycemic control in hyperglycemic patients after cardiovascular surgery. Although twice-daily NPH/regular insulin provided better control than glargine insulin monotherapy, the simplicity and safety of glargine insulin make it an attractive option for the management of postoperative hyperglycemia. Patients with established diabetes will achieve better glucose control with NPH/regular insulin as compared with glargine but have a higher incidence of hypoglycemia.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Cardiovascular Surgical Procedures; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postoperative Complications

To compare the efficacy and safety of two analog insulins as starting regimens in insulin-naïve Type 2 diabetes patients.. In this randomized, open-label parallel study, twice-daily biphasic insulin aspart 30 (30% soluble and 70% protaminated insulin aspart; BIAsp 30) plus metformin (met) was compared with once-daily insulin glargine (glarg) plus glimepiride (glim) in 255 insulin-naïve patients (131 male; mean+/-SD age, 61.2+/-9.1 years). Mean baseline HbA (1c) (+/-SD) was 9.2+/-1.4% and 8.9+/-1.3% for BIAsp 30 plus met ( N=128) and glarg plus glim ( N=127), respectively ( P=0.0747). Primary endpoint was the difference in absolute change in HbA (1c) between groups after 26 weeks of treatment.. HbA (1c) change was significantly greater in the BIAsp 30 plus met group than the glarg plus glim group (between-group difference: -0.5% (95% CI: -0.8; -0.2); P=0.0002). Mean prandial plasma glucose increment was significantly lower for BIAsp 30 plus met compared with glarg plus glim: 1.4+/-1.4 mmol/l vs. 2.2+/-1.8 mmol/l; P=0.0002. During the maintenance phase (weeks 6-26), one major hypoglycemic episode occurred in each group; 20.3% and 9% of patients experienced minor hypoglycemic episodes in the BIAsp 30 plus met and glarg plus glim groups, respectively ( P=0.0124). At end-of-trial, mean daily insulin doses were 0.40 U/kg BIAsp 30 and 0.39 U/kg glarg. Glarg plus glim-treated patients experienced significant weight gain of 1.5 kg (95% CI: 0.84; 2.19; P<0.0001). Weight change with BIAsp 30 plus met of +0.7 kg was not statistically significant (95% CI: -0.07; 1.42; P=0.0762).. Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA (1c) and mean prandial plasma glucose increment to a greater extent than once-daily glarg plus glim.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Treatment Outcome

To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs).. In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naive patients with poor glycemic control (fasting blood glucose [FBG] >/=120 mg/dl, HbA(1c) 7.5-10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Weight Gain

Topics: Blood Glucose; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Sulfonylurea Compounds; Treatment Outcome

To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily in combination with metformin to that of once-daily insulin glargine plus metformin in patients with Type 2 diabetes inadequately controlled with intermediate insulin, or insulin plus oral agent(s) combination therapy.. Ninety-seven patients were randomized in a multicentre, open-label, 32-week crossover study. Primary variables evaluated: haemoglobin A1c (A1c), 2-h post-prandial blood glucose (BG), hypoglycaemia rate (episodes/patient/30 days), incidence (% patients experiencing > or = 1 episode) of overall and nocturnal hypoglycaemia.. At endpoint, A1c was lower with the insulin lispro mixture plus metformin compared with glargine plus metformin (7.54% +/- 0.87% vs. 8.14% +/- 1.03%, P < 0.001). Change in A1c from baseline to endpoint was greater with the insulin lispro mixture plus metformin (-1.00% vs. -0.42%; P < 0.001). Two-hour post-prandial BG was lower after morning, midday, and evening meals (P < 0.001) during treatment with the insulin lispro mixture plus metformin. The fasting BG values were lower with glargine plus metformin (P = 0.007). Despite lower BG at 03.00 hours (P < 0.01), patients treated with the insulin lispro mixture plus metformin had a lower rate of nocturnal hypoglycaemia (0.14 +/- 0.49 vs. 0.34 +/- 0.85 episodes/patient/30 days; P = 0.002), although the overall hypoglycaemia rate was not different between treatments (0.61 +/- 1.41 vs. 0.44 +/- 1.07 episodes/patient/30 days; P = 0.477).. In patients with Type 2 diabetes and inadequate glucose control while on insulin or insulin and oral agent(s) combination therapy, treatment with a twice-daily insulin lispro mixture plus metformin, which targets both post-prandial and pre-meal BG, provided clinically significant improvements in A1c, significantly reduced post-prandial BG after each meal, and reduced nocturnal hypoglycaemia as compared with once-daily glargine plus metformin, a treatment that targets fasting BG.

Topics: Adult; Aged; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Delivery Systems; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Metformin; Middle Aged; Weight Gain

Insulin replacement regimens now stress the importance of administering throughout the day insulin doses that are based on flexible food choices and focusing on improved metabolic control. A flexible multiple daily insulin (FMDI) regimen (premeal lispro plus bedtime glargine) results in lower hemoglobin A1c (HbA1c) levels and fewer hypoglycemic episodes than does a multiple daily insulin (MDI) regimen among school-aged children and adolescents with type 1 diabetes mellitus (DM). The purpose of this study was to determine the feasibility of FMDI therapy for a group of preschool-aged children with type 1 DM who were transitioned from MDI therapy (premeal lispro plus ultralente insulin twice per day), by comparing BMI, total daily insulin requirements, HbA1c levels, and episodes of severe hypoglycemia.. Data were collected over a 2-year period, during quarterly DM clinic visits, from 35 patients (17 female patients and 18 male patients, 4.8 +/- 1.0 years of age) who had received MDI insulin therapy for > or =1 year before being transitioned to a FMDI regimen.. Although there was no significant change in BMI with FMDI therapy (17.1 +/- 1.8 kg/m2 vs 17.0 +/- 1.7 kg/m2), 43% of patients (6 female subjects and 9 male subjects) were overweight (BMI of >85th percentile for age) both before and after treatment. The total daily insulin requirement (0.67 +/- 0.13 U/kg per day vs 0.78 +/- 0.14 U/kg per day) and bolus/basal insulin ratio (1.1 +/- 0.4 vs 1.9 +/- 0.6) were significantly increased and overall glycemic control was improved after transition to FMDI therapy (HbA1c levels: 8.8 +/- 0.9% vs 8.3 +/- 0.8%). However, HbA1c levels improved only among normal-weight subjects (9.0 +/- 1.0% vs 8.3 +/- 1.0%) and not among overweight subjects (8.7 +/- 0.7% vs 8.4 +/- 0.6%) after FMDI therapy. The overall rate of severe hypoglycemia was significantly decreased with the FMDI regimen (25.5 events per 100 patient-years vs 10.6 events per 100 patient-years) but again only for normal-weight children (29.7 events per 100 patient-years vs 7.4 events per 100 patient-years).. The use of FMDI therapy with glargine among preschool-aged children with type 1 DM was associated with improved overall glycemic control and decreased frequency of severe hypoglycemia. Although our study did not have a control group, these findings suggest that FMDI regimens may be a feasible therapeutic alternative to MDI treatment for preschool-aged children with type 1 DM. However, excess body weight status appeared to preclude a desirable therapeutic response in this group of patients.

Topics: Body Mass Index; Child; Child, Preschool; Diabetes Mellitus, Type 1; Feasibility Studies; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Obesity

To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn (NPH) in poorly controlled type 1 diabetes patients.. Patients (n = 125) received preprandial insulin lispro and either glargine (n = 62) or NPH (n = 63) at bedtime for 30 weeks in a multicentre, randomized, single-blind (a blinded investigator made titration decisions) study. Basal insulin dosage was titrated to achieve fasting blood glucose (FBG) values < 5.5 mmol/L.. Baseline characteristics were similar for the two groups (mean diabetes duration 17.5 +/- 10.1 years) except mean glycated haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group (9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was 8.3 versus 9.1% for the glargine versus NPH groups. Adjusted least-squares mean (LSM) change from baseline was -1.04 versus -0.51%, a significant treatment benefit of 0.53% for HbA(1c) in favour of glargine (P < 0.01). Mean baseline FBG were similar for the glargine and NPH groups (11.2 vs 11.4 mmol/L). The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L, with a significant difference of 1.12 mmol/L in favour of glargine (P < 0.05). There were similar total numbers of daytime mild, moderate or severe hypoglycaemia episodes in the two treatment arms. However, significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group (P = 0.04 and P = 0.02).. Glargine is superior to NPH for improving HbA(1c) and FBG levels during intensive insulin therapy in patients with type 1 diabetes, and is associated with less severe nocturnal hypoglycaemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Fasting; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Retrospective Studies; Single-Blind Method; Treatment Outcome

To determine the efficacy and safety of insulin glargine (IG) in children and adolescents with type 1 diabetes. In a prospective, 6-month study, 80 patients, aged 2-19 years, received IG once daily plus insulin regular or rapid analogue before meals. The data of body mass index, frequency of severe hypoglycaemia, daily mean blood glucose, fasting blood glucose, haemoglobin A1c and total daily insulin dosage before and after institution of glargine therapy were collected.. After 6 months, the average HbA1c level in the entire cohort dropped from 7.63+/-0.81 to 7.14+/-0.70% (p<0.001). Fasting blood glucose decreased from 161+/-37 to 150+/-35 mg/dl (p<0.05) in the total group. Severe hypoglycaemic episodes were reduced from 0.18 events per patient in the 6 months before IG therapy to 0.11 events per patient in the 6 months after IG therapy. The total daily insulin dose was reduced in the entire group from 0.90+/-0.32 to 0.83+/-0.29 u/kg/day (p<0.05). Body mass index (BMI) remained unchanged. In the 14 preschooler children, the HbA1c dropped from 7.54+/-0.60 to 6.96+/-0.57% (p<0.05).. Insulin glargine is an efficacious treatment to improve metabolic control in children and adolescents with type 1 diabetes. It also improved the metabolic control in preschool-age children, without increasing the number of hypoglycaemic events.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Prospective Studies; Quality of Life

Topics: Administration, Oral; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Physicians may use either insulin or exenatide injections for patients with type 2 diabetes mellitus who have poor glycemic control despite taking oral blood glucose-lowering drugs.. To compare effects of exenatide and insulin glargine on glycemic control in patients with type 2 diabetes mellitus that is suboptimally controlled with metformin and a sulfonylurea.. 26-week multicenter, open-label, randomized, controlled trial.. 82 outpatient study centers in 13 countries.. 551 patients with type 2 diabetes and inadequate glycemic control (defined as hemoglobin A1c level ranging from 7.0% to 10.0%) despite combination metformin and sulfonylurea therapy.. Exenatide, 10 microg twice daily, or insulin glargine, 1 daily dose titrated to maintain fasting blood glucose levels of less than 5.6 mmol/L (<100 mg/dL).. Hemoglobin A1c level, fasting plasma glucose level, body weight, 7-point self-monitored blood glucose, standardized test-meal challenge, safety, and tolerability.. Baseline mean hemoglobin A1c level was 8.2% for patients receiving exenatide and 8.3% for those receiving insulin glargine. At week 26, both exenatide and insulin glargine reduced hemoglobin A1c levels by 1.11% (difference, 0.017 percentage point [95% CI, -0.123 to 0.157 percentage point]). Exenatide reduced postprandial glucose excursions more than insulin glargine, while insulin glargine reduced fasting glucose concentrations more than exenatide. Body weight decreased 2.3 kg with exenatide and increased 1.8 kg with insulin glargine (difference, -4.1 kg [CI, -4.6 to -3.5 kg]). Rates of symptomatic hypoglycemia were similar, but nocturnal hypoglycemia occurred less frequently with exenatide (0.9 event/patient-year versus 2.4 events/patient-year; difference, -1.6 events/patient-year [CI, -2.3 to -0.9 event/patient year]). Gastrointestinal symptoms were more common in the exenatide group than in the insulin glargine group, including nausea (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) and diarrhea (8.5% vs. 3.0%).. The trial was open-label and did not assess clinical complications related to diabetes. Of the 551 participants, 19.4% of those receiving exenatide and 9.7% of those receiving insulin glargine withdrew from the study. Only 21.6% of the insulin glargine group and 8.6% of the exenatide group achieved the target level for fasting plasma glucose of less than 5.6 mmol/L (<100 mg/dL).. Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine.

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Nausea; Peptides; Venoms; Vomiting

The aim of this study was to evaluate the metabolic effects of continuous subcutaneous insulin infusion (CSII) with flexible multiple daily insulin (FMDI; premeal lispro + bedtime glargine) therapy as determined by glycosylated hemoglobin (HbA1c), body mass index (BMI), and hypoglycemic episodes in a group of patients who made the transition from multiple daily insulin (premeal lispro + bid ultralente) to either CSII or FMDI therapy.. Data from 40 (27 female and 13 male) patients (10.1-17.8 years of age) who were on CSII and 40 age- and gender-matched (27 female and 13 male) patients (10.3-17.3 years of age) who were on FMDI were collected during regularly scheduled visits at a similar frequency over a 1-year period.. The total daily insulin dose did not change in CSII (0.97 +/- 0.24 vs 0.91 +/- 0.22 U/kg) and FMDI (0.98 +/- 0.21 vs 0.97 +/- 0.21 U/kg) patients, whereas the bolus:basal insulin ratio was significantly increased in both CSII (1.01 +/- 0.43 vs 1.32 +/- 0.52) and FMDI (1.07 +/- 0.0.41 vs 1.29 +/- 0.47) patients. The total cohort of CSII patients showed a decrease in HbA1c from 8.4 +/- 1.0% to 7.8 +/- 0.8%, whereas the FMDI cohort did not show a significant change in HbA1c (8.5 +/- 1.1% to 8.2 +/- 0.9%). However, 40% of the CSII group and 22.5% of the FMDI group showed > or =1.0% improvement in HbA1c. Also, a similar number of patients in CSII (52.5%; 8.0 +/- 1.1 to 7.2 +/- 0.5%) and FMDI (47.5%; 8.0 +/- 0.5% to 7.5 +/- 0.4%) maintained or achieved target HbA1c values <8.0%. The BMI increased significantly in the CSII group (21.6 +/- 3.2 vs 23.0 +/- 3.0 kg/m2) but did not change in the FMDI group (21.9 +/- 3.9 vs 22.6 +/- 3.8 kg/m2). There was a significant reduction in the rate of severe hypoglycemia (events/100 patient-years) in both cohorts: 20.6 to 8.2 in the CSII and 18.8 to 7.5 in the FMDI. Similarly, the rate of moderate hypoglycemia decreased in both CSII (68.3-35.4) and FMDI (56.3-30.4).. CSII therapy resulted in a significant improvement in HbA 1c in the entire group, whereas FMDI therapy improved HbA1c in only a subgroup of patients. However, almost half of the patients in each of the treatment groups maintained or achieved target glycemic control. Both CSII and FMDI treatment groups demonstrated a decreased rate of hypoglycemia without an abnormal increase in BMI. Although the design of this study does not allow direct comparison of the metabolic effects of CSII and FMDI therapies, both regimens seem to be superior to basal ultralente and lispro multiple daily insulin regimen and offer desirable therapeutic alternatives in pediatric diabetes care.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Infusions, Parenteral; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin Lispro; Insulin, Long-Acting; Male

Aim of this 1-yr open parallel study was to evaluate the efficacy of two regimens of intensive insulin treatment: continuous s.c. insulin infusion (CSII) and multiple daily insulin injection (MDI) treatment with lispro plus glargine in 48 Type 1 diabetic patients that had been treated with MDI (regular or lispro insulin before each meal plus NPH) for at least 1 yr. Twenty-four patients treated with CSII, receiving lispro at multiple basal infusion rates plus boluses at meal (CSII group), were compared to 24 patients, matched for age, duration of diabetes and metabolic control, treated with MDI with lispro at each meal combined with glargine (glargine group). In the CSII group, compared to traditional MDI treatment, there was a decrease in HbA1c (9.0 +/- 1.3% during traditional MDI vs 8.0 +/- 1.0% during CSII, p<0.001), severe hypoglycaemic episodes (0.42 vs 0.17 per patient/yr, p<0.05), insulin requirement (48 +/- 11.7 vs 35.9 +/- 8.5 U/day, p<0.001). In the glargine group, compared to MDI traditional treatment, there was a decrease in HbA1c (8.6 +/- 1.1 vs 7.9 +/- 1.2%, p<0.001) and severe hypoglycaemic episodes (0.46 vs 0.21 per patient/yr, p<0.05). No significant difference between the CSII group and the glargine group was present in the degree of improvement in HbA1c and severe hypoglycaemic episodes. However, in the CSII group there was a significantly greater reduction in mean amplitude of glycaemic excursions (MAGE) and insulin requirement than in the glargine group. In conclusion, despite a similar improvement in metabolic control, CSII improves blood glucose variability when compared to MDI with glargine as basal insulin.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Triglycerides

To see if insulin glargine improves glycemic control in a clinical setting.. A questionnaire and electronic database were used to assess glycemic parameters for 292 type 1 diabetic subjects taking > or =4 injections per day and receiving glargine as their only long-acting basal insulin for at least 6 months. Sixty-three subjects were taking glargine in the morning, 125 were taking glargine in the evening, and 104 were splitting the glargine dose between the morning and evening.. The mean (+/-S.D.) age and duration of diabetes were 32 +/- 10 years and 15.9 +/- 10.3 years, respectively. The mean (+/-S.E.M.) durations of treatment with glargine were 13.1 +/- 0.6 months, 12.2 +.- 0.4 months, and 14.3 +/- 0.5 months for the morning, evening, and split treatment groups, respectively (P < 0.01). The A1C values improved significantly from baseline for the evening and the split dosage groups or when all groups were combined. The mean basal insulin dose was significantly reduced at the end of the study in all the three groups from baseline with no change in the short-acting insulin dose. The number of severe hypoglycemic episodes decreased from 379 in the year prior to glargine treatment to 167 in the post-glargine year. The weight gain was significantly higher in the group that took the split glargine dose (P < 0.01).. Similar or improved glycemic control was achieved by administering glargine in the morning, evening, or using a split dose without any further increase in severe hypoglycemic episodes. Splitting the glargine dose did not offer any advantages in glycemic control parameters.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Time Factors

Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH.. One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment.. Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05).. The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cognition; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male

The goal of new therapies introduced for type 1 diabetes should be to decrease hypoglycemic episodes while improving glycemic control.. A database was used to computer match the baseline A1C values in 196 subjects with type 1 diabetes receiving multiple daily injections (MDI) consisting of four or more injections per day. There were 98 patients transferred from NPH to insulin glargine (Lantus, Aventis Pharmaceuticals, Bridgewater, NJ), and 98 patients remained on NPH throughout the study. The gender distribution and mean age (approximately 32 years), duration of diabetes (approximately 16 years), and duration of treatment (approximately 13 months) were not significantly different between the groups. The majority of patients were well controlled (>50% in both groups had an A1C <7%).. The mean A1c values were not significantly different in the groups at baseline or at follow-up. Severe hypoglycemic episodes per patient per year were significantly lower in the glargine group compared with the NPH group (0.5 vs. 1.2, respectively; P = 0.04). The mean end-of-study total (P = 0.03) and long-acting (P = 0.0001) doses were significantly reduced from baseline in the group that switched to glargine, but not in the group that remained on NPH, with no change in the short-acting dose in either group. The weight gain was significantly higher in the NPH group at the end of the study (P = 0.004) with no significant change in the glargine group.. Transfer to glargine treatment from NPH in MDI regimens significantly reduces severe hypoglycemic episodes despite a decline in long-acting basal insulin without significant weight gain.

Topics: Adult; Databases, Factual; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Time Factors

To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin.. In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study.. Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA(1c) levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13).. Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.

Topics: Adolescent; Blood Glucose; Blood Glucose Self-Monitoring; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male

The aim of the trial was to compare the efficacy and safety of the new, long-acting basal insulin, insulin glargine (LANTUS(R)), with NPH human insulin, each administered in a combination regimen with oral antidiabetic drugs in patients with Type 2 diabetes.. In a multicentre, open, randomised study, 570 patients with Type 2 diabetes, aged 34 - 80 years, were treated for 52 weeks with insulin glargine or NPH insulin given once daily at bedtime. Previous oral antidiabetic therapy was continued throughout the study.. There was a clinically relevant decrease in glycosylated haemoglobin (GHb) values from baseline to endpoint with both drugs (insulin glargine: - 0.46 %; NPH insulin: - 0.38 %; p = 0.415); also, this difference was statistically significant in the subgroup of overweight patients with BMI > 28 kg/m 2 (insulin glargine: - 0.42 %, NPH insulin: - 0.11 %; p = 0.0237). Over the entire treatment period, NPH insulin-treated patients (41 %) and insulin glargine-treated patients (35 %) experienced a similar level of symptomatic hypoglycaemia. A statistically significant difference was observed in the number of patients treated with NPH insulin who reported at least one episode of nocturnal hypoglycaemia compared with those treated with insulin glargine in the overall population and in the overweight subgroup (overall: 24 % vs. 12 %, p = 0.002; overweight: 22.2 % vs. 9.5 %, p = 0.0006), using the Cochran-Mantel-Haenszel test. These differences were most pronounced in insulin-naïve and overweight (BMI > 28 kg/m 2) sub-groups. The incidence of adverse events was similar for the two treatments.. This study demonstrated that insulin glargine is as effective as NPH insulin in achieving glycaemic control in patients with Type 2 diabetes, and is associated with fewer episodes of symptomatic hypoglycaemia, particularly nocturnal episodes.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Insulin glargine (Lantus), a long-acting human insulin analog, provides effective glycemic control when administered at bedtime. This open-label, randomized, parallel group, multicenter study investigated whether insulin glargine is equally effective if administered before breakfast, before dinner, or at bedtime.. Patients with type 1 diabetes on basal-bolus therapy (n = 378, 18-68 years, HbA(1c) 5.5-9.8%) were treated with once-daily individually titrated insulin glargine in combination with prandial insulin lispro for 24 weeks.. Baseline characteristics were similar in the three groups (overall age 40.9 +/- 11.9 years, diabetes duration 17.3 +/- 11.5 years). Median total daily insulin dose was similar at baseline (0.65, 0.65, and 0.66 IU/kg for breakfast, dinner, and bedtime, respectively) and remained relatively constant over the study period; however, the insulin glargine-to-total insulin dose ratio increased more in the breakfast group than in the dinner and bedtime groups. A similar reduction of adjusted mean HbA(1c) from baseline to end point occurred in all patients (7.6-7.4, 7.6-7.5, and 7.6-7.5% for breakfast, dinner, and bedtime, respectively), and a similar percentage achieved HbA(1c) <7.0% at end point in all groups (29.5, 29.8, and 25.8%, respectively). The 24-h blood glucose profiles in relation to injection time were similar in all groups. The incidences of total symptomatic and severe hypoglycemia did not differ between the three treatment groups; however, nocturnal hypoglycemia occurred in significantly fewer patients in the breakfast group (59.5%) compared with the dinner (71.9%) and bedtime (77.5%) groups (P = 0.005).. These data suggest that insulin glargine, in combination with insulin lispro, is safe and effective when administered before breakfast, before dinner, or at bedtime.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Selection; Quality of Life; Safety; Time Factors

Patients with type 2 diabetes are often treated with oral antidiabetic agents plus a basal insulin.. To investigate the efficacy and safety of glimepiride combined with either morning or bedtime insulin glargine or bedtime neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes.. Open-label, randomized, controlled trial.. 111 centers in 13 European countries.. 695 patients with type 2 diabetes who were previously treated with oral antidiabetic agents.. Randomization to treatment with morning insulin glargine, bedtime NPH insulin, or bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride. The insulin dose was titrated by using a predefined regimen to achieve fasting blood glucose levels of 5.56 mmol/L or lower (< or =100 mg/dL).. Hemoglobin A(1c) values, blood glucose levels, insulin dose, and body weight.. Hemoglobin A(1c) levels improved by -1.24% (two-sided 90% CI, -1.10% to -1.38%) with morning insulin glargine, by -0.96% (CI, -0.81% to -1.10%) with bedtime insulin glargine, and by -0.84% (CI, -0.69% to -0.98%) with bedtime NPH insulin. Hemoglobin A(1c) improvement was more pronounced with morning insulin glargine than with NPH insulin (0.40% [CI, 0.23% to 0.58%]; P = 0.001) or bedtime insulin glargine (0.28% [CI, 0.11% to 0.46%]; P = 0.008). Baseline to end-point fasting blood glucose levels improved similarly in all three groups. Nocturnal hypoglycemia was less frequent with morning (39 of 236 patients [17%]) and bedtime insulin glargine (52 of 227 patients [23%]) than with bedtime NPH insulin (89 of 232 patients [38%]) (P < 0.001).. The risk for nocturnal hypoglycemia was lower with glimepiride in combination with morning and bedtime insulin glargine than with glimepiride in combination with bedtime NPH insulin in patients with type 2 diabetes. Morning insulin glargine provided better glycemic control than did bedtime insulin glargine or bedtime NPH insulin.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Risk Factors; Sulfonylurea Compounds; Weight Gain

To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA(1c).. In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG)

Topics: Administration, Oral; Adult; Aged; Algorithms; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

The pediatric diabetes team at the University of Minnesota made a clinical decision to switch patients with type 1 diabetes with a hemoglobin A1c level greater than 8.0% to insulin glargine in an effort to improve glycemic control. Retrospective chart analysis was performed on 37 patients 6 months after the switch to insulin glargine therapy.. After 6 months, the average hemoglobin A1c level in the entire cohort dropped from 10.1 +/- 2.0 to 8.9 +/- 1.6% (p = 0.001). Thirty patients responded with an average hemoglobin A1c drop of 1.7 +/- 1.5%, from 10.3 +/- 2.2 to 8.6 +/- 1.5% (p < 0.001). Seven patients did not respond to insulin glargine therapy, with an average hemoglobin A1c rise of 1.0 +/- 0.8% from a baseline of 9.5 +/- 1.0% to 10.4 +/- 1.4% (p = 0.01). The greatest response was seen in children with an A1c > 12.0%, who dropped their hemoglobin A1c by 3.5 +/- 1.9%. Compared with responders, non-responders had significantly less contact with the diabetes team in the form of clinic visits and telephone conversations both before and after initiation of glargine therapy. Sixty-two per cent of patients received insulin glargine at lunchtime, when injections could be supervised at school. Three episodes of severe hypoglycemia occurred after initiation of insulin glargine therapy.. Insulin glargine substantially improved glycemic control in children and adolescents with poorly controlled type 1 diabetes. This response was most remarkable in those with a baseline hemoglobin A1c level > 12.0%, and may have been related to increased supervision of injections.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male

The purpose of this study was to evaluate the use of a new long-acting basal insulin, insulin glargine (IG), in children with type 1 diabetes. Study design Data from 114 subjects, age 2 to 18 years (mean, 12.2 years; 54 boys, 60 girls), were collected for 9 months before and 9 months after IG treatment. During IG therapy, all subjects received morning neutral protamine Hagedorn insulin (given with insulin lispro; Humalog) to provide daytime insulin coverage. The numbers of nonsevere and severe hypoglycemic events, hemoglobin A1c values, body weight, and daily insulin dose were recorded at each clinic visit.. The mean (+/-1 SEM) frequency of nonsevere hypoglycemic events per week decreased from 2.0+/-0.1 to 1.3+/-0.1 (P<.001). Severe hypoglycemic episodes were reduced from a total of 22 in the 9 months before IG to nine in the 9 months after IG. Severe nocturnal events were similarly reduced from 14 to four episodes. The mean (+/-1 SEM) hemoglobin A1c levels were 9.6+/-0.1% (baseline), 9.4+/-0.1% at 3 months (P=.18), 9.3+/-0.1% at 6 months (P=.03), and 9.3+/-0.1% at 9 months (P=.01).. Insulin glargine therapy can reduce hypoglycemic episodes in children and adolescents with suboptimal glucose control without jeopardizing glycemic control.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male

To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone.. A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily in = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose <6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg.. The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis. The mean change (means +/- SD) in HbA1c from baseline to end point was similar in the insulin glargine group (-0.41 +/- 0.1%) and the NPH group (-0.59 +/- 0.1%) after patients began with an average baseline HbA1c of approximately 8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.%) However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase(26.5 vs. 35.5%, P = 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P < 0.0007).. In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin.

Topics: Blood Glucose; Body Mass Index; Circadian Rhythm; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Risk Factors; Time Factors

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin.. This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l.. A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P > 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level <2.0 mmol/l compared with subjects receiving NPH insulin.. Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Time Factors

HOE 901 (Hoechst Marion Roussel, Frankfurt, Germany) is a biosynthetic insulin with a prolonged action. The aim of this study was to compare the effect of the long-acting insulin analog HOE 901 with NPH insulin regarding glycemic control in patients with type 1 diabetes.. A total of 333 type 1 diabetic patients were enrolled in this multinational parallel group trial. Subjects were randomized either to two different formulations of HOE 901 (the formulations differed only in zinc content) or to NPH insulin. The study was only partially blinded because patients can distinguish HOE 901 (a clear solution) from NPH (a cloudy suspension). In addition to premeal injections of regular insulin, patients received HOE 901 at bedtime or NPH once daily at bedtime or twice daily in the morning and at bedtime.. Fasting plasma glucose levels were significantly lower with HOE 901 (-1.88 mmol/l. P = 0.0005) as were fasting self-monitored blood glucose levels (-0.80 mmol/l, P = 0.0020). HbA1c levels also showed a significant reduction with HOE 901 (-0.14%) versus NPH (P = 0.030). The overall frequency of hypoglycemia did not differ, but the frequency of nocturnal hypoglycemia was significantly (P = 0.0037) lower with HOE 901 (36 vs. 55%). However, this effect on nocturnal hypoglycemia was significant only versus NPH once daily not NPH twice daily. The pattern of adverse events and injection site reactions with HOE 901 was similar to that with NPH.. This study indicates that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks, and HOE 901 has a possible safety benefit in terms of nocturnal hypoglycemia.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Female; Fructosamine; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Safety; Single-Blind Method

Available basal insulin formulations do not provide a constant and reliable 24-h insulin supply. We compared the efficacy and safety of glargine (a long-acting insulin analog) and NPH insulins in insulin-naive type 2 diabetic patients treated with oral antidiabetic agents.. There were 426 type 2 diabetic patients (age 59 +/- 9 years, BMI 28.9 +/- 4.3 kg/m2, mean +/- SD) with poor glycemic control on oral antidiabetic agents randomized to treatment for 1 year with bedtime insulin glargine or bedtime NPH insulin. Oral agents were continued unchanged. The fasting blood glucose (FBG) target was 6.7 mmol/l (120 mg/dl).. Average glycemic control improved similarly with both insulins (HbA(1c), [reference range <6.5%] 8.3 +/- 0.1 vs. 8.2 +/- 0.1% at 1 year, glargine vs. NPH, mean +/- SEM, P < 0.001 vs. baseline for both). However, there was less nocturnal hypoglycemia (9.9 vs. 24.0% of all patients, glargine vs. NPH, P < 0.001) and lower post-dinner glucose concentrations (9.9 +/- 0.2 vs. 10.7 +/- 0.3 mmol/l, P < 0.02) with insulin glargine than with NPH. Insulin doses and weight gain were comparable. In patients reaching target FBG, HbA(1c) averaged 7.7 and 7.6% in the glargine and NPH groups at 1 year.. Use of insulin glargine compared with NPH is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels. These data are consistent with peakless and longer duration of action of insulin glargine compared with NPH. Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target < or =6.7 mmol/l. These data support use of insulin glargine instead of NPH in insulin combination regimens in type 2 diabetes.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Triglycerides

To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes.. Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime.. Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (< 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034).. Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Therapy, Combination; Ethnicity; Fasting; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Male; United States

Glargine, a product of recombinant technology, has different structural and physicochemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine.. Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min(-1)) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies.. The peak total symptoms scores (mean +/- s.e.m.) at nadir blood glucose (2.5 mmol/1) were 18.83 +/- 2.68 (healthy) and 17.46 +/- 3.62 (diabetic) during regular insulin, and 18.50 +/- 3.20 (healthy) and 19.08 +/- 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 +/- 140.4 pg/ml (regular insulin) and 608.8 +/- 129.9 pg/ml (glargine) among healthy subjects, and 332.5 +/- 54.8 pg/ml (regular insulin) and 321.8 +/- 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal.. We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Epinephrine; Female; Glucagon; Glucose Clamp Technique; Heart Rate; Human Growth Hormone; Humans; Hydrocortisone; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Norepinephrine; Recombinant Proteins; Reference Values

Diabetes control without developing hypoglycemia is challenging in Type 1 diabetes (T1D) management, with few studies evaluating the effect of insulin glargine timing on glucoregulation.. The aim is to compare glycemic control using continuous glucose monitoring (CGM) in children with T1D receiving bedtime versus morning glargine and to assess CGM effect on glycemia.. This cross-sectional observational study was conducted on 30 pediatric patients with T1D receiving glargine (19 at bedtime and 11 in the morning). CGM sensor was applied for 3-5 days using the I-Pro2 blood glucose sensor.. Total daily dose of glargine showed a significant correlation with HbA1C (p=0.006) and percentage of glucose readings within average (p=0.039). HbA1C correlated significantly with time in range (TIR) (p=0.049). Nocturnal hypoglycemia was significantly higher in the bedtime glargine group than in the morning one (p=0.016). The morning glargine group showed better control in terms of lower HbA1C and higher TIR, but these did not reach statistical significance. Follow- up after 3 months revealed significant improvement in the percentage of hyperglycemia, BG readings within average, as well as HbA1c (p:0.001).. Bedtime glargine administration was associated with a higher frequency of occurrence of nocturnal hypoglycemia. No statistically significant difference in glycemic control between both groups was found. CGM use improved glycemic control.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Egypt; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Insulin remains a mainstay of treating hyperglycemia in an acute setting. Insulin glargine 300 units/mL (Toujeo, iGlar300) has a different pharmacokinetic profile than 100 units/mL basal insulins, such as insulin detemir (iDet100) and iGlar100. While conversion from iGlar300 to iGlar100 requires a 20% dose decrease, there is currently no recommended interchange from iGlar300 to iDet100.. Compare the incidence of hypoglycemia in patients who received a 1:1 unit interchange from home iGlar300 or iGlar100 to iDet100 while admitted.. A retrospective study was conducted to evaluate adults within a multi-site network admitted between May and December 2019. Patients were included if they received at least one dose of iDet100 following interchange from home iGlar300 or iGlar100. The primary endpoint was the incidence of hypoglycemic events following a 1:1 interchange of iGlar300 vs. iGlar100 to inpatient iDet100. Secondary outcomes include overall hypoglycemic events, time to hypoglycemia, and doses given before hypoglycemia.. Of 615 patients, 394 received a 1:1 unit interchange to iDet100 (52 from iGlar300 and 342 from iGlar100). Incidence of hypoglycemic events was significantly higher in those with a 1:1 interchange from iGlar300 versus iGlar100 (36.5% vs. 18.7%, p = 0.007). Significant differences were observed in overall hypoglycemic events, time to hypoglycemia, and number of doses given before hypoglycemic event.. A 1:1 unit interchange from iGlar300 to iDet100 led to a higher incidence of hypoglycemic events compared to those interchanged from iGlar100. Dose reduction should be considered when transitioning from home iGlar300 to iDet100 in the inpatient setting.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Retrospective Studies

To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics.. SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function.. No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P > 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P = 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events.. Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine

To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method.. This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets.. Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia.. Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Male

To compare outcomes in adults with type 2 diabetes (T2D) suboptimally controlled with basal insulin who initiated treatment with iGlarLixi or premixed insulin.. This retrospective real-world analysis was conducted using data from adults (age ≥ 18 years) with T2D in the US Optum Clinformatics database who had previously received basal insulin and newly initiated iGlarLixi or premixed insulin. Cohorts were propensity-score matched on baseline characteristics using a greedy nearest neighbour-matching algorithm, and outcomes were assessed at 12 months. Subgroup analyses were performed for those aged 65 years or older and those with a baseline HbA1c of 9% or higher. The primary endpoint was treatment persistence in the overall population. Secondary endpoints were treatment adherence, healthcare resource utilization (HRU), costs, hypoglycaemia events and change in HbA1c from baseline.. Each cohort comprised 834 participants. In the overall population, treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus premixed insulin: 42.5% versus 39.1%; hazard ratio 0.88; 95% confidence interval 0.778-0.998; P = .0465. Adherence and HbA1c reduction were similar between groups, whereas hypoglycaemia events, HRU and costs were numerically lower for iGlarLixi. Outcomes in both the age 65 years or older subgroup and in those with an HbA1c of 9% or higher were consistent with those for the overall population.. In this observational study in people with T2D suboptimally controlled on basal insulin, once-daily iGlarLixi was an effective treatment alternative to premixed insulin with significantly higher treatment persistence, similar adherence and HbA1c reduction, and numerically lower hypoglycaemia events, HRU and costs, regardless of age or baseline HbA1c.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Retrospective Studies

Insulin preparations, which are drug treatments for diabetes, cause fatal hypoglycemia when an overdose is administered. Cases of homicide and suicide using these preparations have been reported and are of great forensic interest. However, there are few reports assessing the postmortem concentration of insulin preparations, and it is often difficult to determine the cause of death. In the present study, we report a case of a suspected insulin glargine and insulin lispro overdose for suicide. A woman in her 30s had a history of mental illness and diabetes. The day before her death, she reported to her boyfriend that she had taken large doses of insulin preparations and prescription drugs. An autopsy revealed no fatal injuries or lesions. Drug screening tests revealed several prescription drugs, none of which showed toxic concentrations. Analysis using LC-MS/MS detected insulin glargine in the peripheral and cardiac blood at 429 μU/mL and 1362 μU/mL, respectively, whereas insulin lispro was detected in both the peripheral and cardiac blood at levels below the lower limit of quantification (LLOQ; <50 μU/mL). The cause of death was considered likely to be hypoglycemia caused by an overdose of insulin glargine. Insulin glargine is rapidly metabolized after subcutaneous administration and is rarely detected in the blood when used at therapeutic doses. There are no other reports on the quantification of insulin glargine parent compounds in postmortem samples, and this case provides important data on postmortem blood concentrations of insulin glargine intoxication.

Topics: Blood Glucose; Chromatography, Liquid; Diabetes Mellitus; Drug Overdose; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Tandem Mass Spectrometry

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group.. Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group.. • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic.. • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Child, Preschool; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane

To prevent hypoglycemic episodes, the management of insulin therapy against post-transplant diabetes mellitus (PTDM) is important. We compared glargine (long-acting insulin) versus NPH isophane (intermediate-acting insulin) as an armamentarium against PTDM. Indeed, the study evaluated PTDM patients with hypoglycemic episodes treated with isophane or glargine.. We evaluated a total number of 231 living-donor renal transplant recipients with PTDM of age ≥ 18 years admitted to the hospital between January 2017 and September 2021. However, patients taking hypoglycemic agents before transplantation were excluded from this study. Out of 231 patients, 52 (22.15%) suffered from PTDM out of whom 26 were treated with glargine or isophane.. After applying exclusion criteria, out of 52 PTDM patients 23 were included in the study: 13 PTDM patients were treated with glargine, whereas 10 PTDM patients with isophane. Our analysis revealed 12 episodes of hypoglycemia in glargine-treated PTDM patients compared to 3 in isophane-treated PTDM patients (p = 0.056). Clinically, 9 out of 15 hypoglycemic episodes were nocturnal (60%). Furthermore, no other risk factors were observed in our study population. Detailed analysis showed that both groups had equivalent doses of immunosuppressants and oral hypoglycemic agents. The odds ratio for hypoglycemia in the group treated with isophane compared to that treated with glargine was 0.224 (95% CI, 0.032-1.559). Glargine users recorded significantly lower blood sugar levels before lunch, dinner and at bedtime with p-values of 0.001, 0.009 and 0.001 respectively. A better hemoglobin A1c (HbA1c) level was seen in the glargine vs. isophane group (6.98 ± 0.52 vs. 7.45 ± 0.49, p-value 0.03).. The study shows better blood sugar control with long-acting insulin analog, glargine, than with intermediate-actin analog, isophane. Overall, a higher number of hypoglycemic episodes was nocturnal. Long term safety of long-acting insulin analogs needs to be further studied.

Topics: Adolescent; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Recent advances in Automated Insulin Delivery systems have been shown to dramatically improve glycaemic control and reduce the risk of hypoglycemia in people with type 1 diabetes. However, they are complex systems that require specific training and are not affordable for most. Attempts to reduce the gap with closed-loop therapies using advanced dosing advisors have so far failed, mainly because they require too much human intervention. With the advent of smart insulin pens, one of the main constraints (having reliable bolus and meal information) disappears and new strategies can be employed. This is our starting hypothesis, which we have validated in a very demanding simulator. In this paper, we propose an intermittent closed-loop control system specifically intended for multiple daily injection therapy to bring the benefits of artificial pancreas to the application of multiple daily injections.. The proposed control algorithm is based on model predictive control and integrates two patient-driven control actions. Correction insulin boluses are automatically computed and recommended to the patient to minimize the duration of hyperglycemia. Rescue carbohydrates are also triggered to avoid hypoglycemia episodes. The algorithm can adapt to different patient lifestyles with customizable triggering conditions, closing the gap between practicality and performance. The proposed algorithm is compared with conventional open-loop therapy, and its superiority is demonstrated through extensive in silico evaluations using realistic cohorts and scenarios. The evaluations were conducted in a cohort of 47 virtual patients. We also provide detailed explanations of the implementation, imposed constraints, triggering conditions, cost functions, and penalties for the algorithm.. The in-silico outcomes combining the proposed closed-loop strategy with slow-acting insulin analog injections at 09:00 h resulted in percentages of time in range (TIR) (70-180 mg/dL) of 69.5%, 70.6%, and 70.4% for glargine-100, glargine-300, and degludec-100, respectively, and injections at 20:00 h resulted in percentages of TIR of 70.5%, 70.3%, and 71.6%, respectively. In all the cases, the percentages of TIR were considerably higher than those obtained from the open-loop strategy, being only 50.7%, 53.9%, and 52.2% for daytime injection and 55.5%, 54.1%, and 56.9% for nighttime injection. Overall, the occurrence of hypoglycemia and hyperglycemia was notably reduced using our approach.. Event-triggering model predictive control in the proposed algorithm is feasible and may meet clinical targets for people with type 1 diabetes.

Topics: Algorithms; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Glycemic Control; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Pancreas, Artificial

To evaluate the effectiveness and safety profile of switching to insulin glargine 300 U/mL (Gla-U300) in patients with uncontrolled type 2 diabetes (T2D) on basal insulin in Saudi Arabia.. We conducted a multicentre retrospective study that retrieved the medical records of adult T2D patients switched to Gla-U300 because of poor glycaemic control on their basal insulin. Data covering 6 months ± 30 days before and after the switch were retrieved.. Data from 718 patients were analysed. The mean HbA1c decreased significantly 6 months after switching to Gla-U300, with a mean reduction of 0.7% (95% confidence interval [CI] 0.6%-0.9%; P < .001). The percentage of patients with HbA1c levels of less than 7% increased from 6.4% before switching to 10.3% after switching to Gla-U300. The percentage of patients achieving the predefined individualized HbA1c goal increased from 8.6% before switching to 17.3% after switching to Gla-U300. The mean daily insulin dose decreased from a baseline level of 32.2 (± 14.7) to 31.0 (± 15) U (P = .09). About 36.1 of the patients required adjustment to the initial dose. Gla-300 was well tolerated; 4.5% of the patients experienced overall confirmed or symptomatic hypoglycaemia, compared with 15.3% before switching to Gla-U300. The incidence of severe hypoglycaemia after switching was 0.6% (n = 4 patients), compared with 1% before switching.. Real-world evidence supports the effectiveness of switching to Gla-U300 from first-generation basal insulin in T2D in Saudi Arabia.

Topics: Adult; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Retrospective Studies; Saudi Arabia; Treatment Outcome

A 58-year-old Japanese man was brought to the emergency room due to disturbance of consciousness. He regained consciousness on the day of admission and started taking hospital meals, but he needed intravenous glucose administration for eight days. The total amount of glucose administration was 4,464 g. It took over three weeks for exogenous insulin to be almost undetectable. While degludec binds to albumin and exerts glucose-lowering effects for a long time, the above-mentioned period of three weeks was consistent with the half-life of albumin. Hypoglycemia induced by massive dose of insulin degludec is persistent and prominent.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

This study evaluated the effectiveness and safety of switching the basal insulin (BI) in a BI-supported oral therapy (BOT) to insulin glargine 300 U/ml (Gla-300) in adults with inadequately controlled type 2 diabetes (T2D).. This was a non-interventional, multicentre, prospective 12-month study, conducted in Germany, Austria and Switzerland. The study documented people with T2D with glycated haemoglobin (HbA1c) between 7.5% and 10.0%, currently treated by a non-Gla-300 BOT regimen, after the physician had decided to switch the BI to Gla-300. Primary endpoint was the proportion of patients achieving the fasting plasma glucose (FPG; ≤110 mg/dl) target.. In total, 1194 participants comprised the full analysis set, of which 793 completed documentation of 12 months Gla-300 treatment (FAS-M12). The main previous BI was insulin glargine 100 U/ml (Gla-100; 47.2%). Twelve months after switching to Gla-300, 27.0% of FAS-M12 participants achieved the FPG target and 44.8% their individualized HbA1c target. The greatest FPG target achievements were seen in previous Gla-100 (29.3%), and greatest HbA1c target achievements in previous insulin detemir users (57.7%). The mean FPG decreased by -36.3 ± 51.2 mg/dl to 135.5 ± 36.9 mg/dl and mean HbA1c by -0.79 ± 1.01% to 7.45 ± 0.94%. Symptomatic and nocturnal hypoglycaemia incidence significantly decreased over 12 months of Gla-300 treatment. Body weight remained unchanged.. Switching the BI to Gla-300 in a BOT regimen improved metabolic control and treatment satisfaction in a substantial proportion of patients with T2D and inadequate target achievement within 12 months in clinical practice with a decreased risk of symptomatic and nocturnal hypoglycaemia and without weight gain.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Prospective Studies

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

Recent development of novel antidiabetic drugs with proven cardiovascular (CV) and renal benefit and positive effect on body weight enable to take a more complex approach toward the management of type 2 diabetes mellitus (T2DM). Fixed-ratio combinations of insulin-GLP-1 receptor agonist (FRC) utilize complementary mechanisms of action of their individual components and address multiple pathologies linked with T2DM at the same time.. There are currently three FRCs on the market: iGlarLixi (glargine and lixisenatide in 2 different formulations) and IDegLira (degludec and liraglutide). We provide an up-to-date review on the rationale for the use of FRCs and their current position in the management of T2DM. We discuss the available evidence from randomized controlled trials, post hoc analyses, indirect comparative studies and real-world data on their effect on glycemic control, risk of hypoglycemia, body weight, CV safety, and their safety profile.. FRCs represent an efficacious option for treatment intensification from basal insulin or even the first insulin-based therapy in T2DM. Their excellent glucose-lowering efficacy is complemented with lower risk of hypoglycemia in comparison to basal insulin, neutral effect on body weight and the lower risk of gastrointestinal adverse effects in comparison to GLP-1 receptor agonists.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

DHA has been shown to be neuroprotective and important to neurogenesis, but its role in HG-induced brain injury and the underlying mechanisms remain unknown. To elucidate the therapeutic effect of DHA, we established a mouse model with insulin-induced hypoglycemic brain injury and an in vitro model of HT-22 cells using a sugar-free medium. DHA treatment significantly reduced neuronal death and improved HG-induced learning and memory deficits. Moreover, DHA inhibited neuronal necroptosis and decreased the concentrations of TNF-α, IL-1β and TNFR1. DHA also activated PPAR-γ and suppressed the NF-κB pathway in mouse brain tissues. In vitro, DHA treatment restored the viability and decreased necroptosis of HT-22 cells treated with glucose deprivation. However, the inhibition of PPAR-γ with T0070907 reversed neuroprotective and anti-necroptosis effects of DHA in HG-induced brain injury, which is associated with the activation of the downstream NF-κB pathway. We conclude that DHA displays a protective effect against HG-induced brain injury through the PPAR-γ/NF-κB pathway and represents a promising method to prevent HG-induced brain injury.

Topics: Animals; Cell Line; Docosahexaenoic Acids; Hypoglycemia; Insulin Glargine; Interleukin-1beta; Mice; Necroptosis; Neurons; NF-kappa B; PPAR gamma; Receptors, Tumor Necrosis Factor, Type I; Signal Transduction; Tumor Necrosis Factor-alpha

To compare 12-month clinical effectiveness of insulin glargine 300 units/mL (Gla-300) versus first-generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla-100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla-300 or Gla-100/IDet) in a real-world setting.. DELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla-300 (Gla-300 switchers) and were propensity score-matched (1:1) to patients who switched to Gla-100 or IDet (Gla-100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all-hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact).. HbA1c reductions were similar following switching to Gla-300 or Gla-100/IDet (-0.51% vs. -0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all-hypoglycaemia incidence and event rates. However, the Gla-300 switcher cohort had a significantly lower risk of inpatient/ED-associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60-0.89; p = .002) and experienced significantly fewer inpatient/ED-associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001).. In patients with T2D at high risk of hypoglycaemia, switching to Gla-300 or Gla-100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla-300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Insulin; Insulin Glargine; Retrospective Studies; United States

This study aimed to retrospectively compare the clinical efficacy of different types of long-acting insulin therapies-glargine U100, glargine U300, degludec, and insulin degludec/insulin aspart-among Japanese patients with type 2 diabetes after insulin use was initiated in an outpatient setting. The study consisted of 822 insulin-naïve patients in Japan who started using long-acting insulin for treatment of type 2 diabetes and continued for over 12 months. In addition, the impact of insulin type on insulin withdrawal was investigated by dividing the participants into two groups: those who achieved insulin withdrawal and those who did not, during the 12-month observation period based on a Cox proportional hazards model. As a result, HbA1c was decreased, and BMI was increased in all participants regardless of the insulin type used. A total of 185 participants succeeded in insulin withdrawal. After adjustment was made for several confounders, the positive determinant factors for withdrawal were short duration of diabetes and the choice of IDegAsp when compared with Gla100; the negative determinant factor was use of insulin secretagogues at the start of the study. In conclusion, all long-acting insulins were a powerful tool for treatment of type 2 diabetes, and patients with short duration of diabetes and/or no usage of insulin secretagogues resulted in favorable outcomes in terms of insulin withdrawal within a year in an outpatient setting. In addition, insulin degludec/insulin aspart was found to possibly be a better choice for treatment when it was compared with glargine U100 among the four types of insulin.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Japan; Retrospective Studies; Secretagogues

To provide real-world data on the addition of basal insulin (BI) in people with type 2 diabetes mellitus (PWD2) suboptimally controlled with glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. However, real-world data on the addition of BI to GLP-1RA therapy are limited.. We used a US electronic medical record data source (IBM® Explorys®) that includes approximately 4 million PWD2 to assess the real-world impact of adding the second-generation BI analogue insulin glargine 300 U/mL (Gla-300) to GLP-1RA therapy. Insulin-naïve PWD2 receiving GLP-1RAs who also received Gla-300 between March 1, 2015 and September 30, 2019 were identified; participants were required to have data for ≥12 months before, and ≥6 months after, addition of Gla-300.. The mean (standard deviation [SD]) age of participants (N = 271) was 57.9 (10.8) years. Baseline glycated haemoglobin (HbA1c) was 9.16% and was significantly reduced (-0.97 [SD 1.60]%; P < 0.0001) after addition of Gla-300; a significant increase in the proportion of PWD2 achieving HbA1c control was observed after addition of Gla-300 (HbA1c <7.0%: 4.80% vs. 22.14%, P < 0.0001; HbA1c <8.0%: 19.56% vs. 51.29%, P < 0.0001). The incidence of overall (8.49% vs. 9.59%; P = 0.513) and inpatient/emergency department (ED)-associated hypoglycaemia (0.37% vs. 0.74%; P = 1.000), as well as overall (0.33 vs. 0.46 per person per year [PPPY]; P = 0.170) and inpatient/ED-associated hypoglycaemia events (0.01 vs. 0.04 PPPY; P = 0.466) were similar before and after addition of Gla-300.. In US real-world clinical practice, adding Gla-300 to GLP-1RA significantly improved glycaemic control without significantly increasing hypoglycaemia in PWD2. Further research into the effect of adding Gla-300 to GLP-1RA therapy is warranted.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Middle Aged

To assess the effectiveness and safety of insulin glargine and lixisenatide (iGlarLixi) fixed-ratio combination on a cohort of Romanian adults with type 2 diabetes (T2D).. Open-label, 24-week, prospective cohort study.. 65 secondary care diabetes centres in Romania.. The study included 901 adults with T2D suboptimally controlled with previous oral antidiabetic drugs (OADs)±basal insulin (BI) who initiated treatment with iGlarLixi upon the decision of the investigator. Major exclusion criteria were iGlarLixi contraindications and refusal to participate. 876 subjects received at least one dose of iGlarLixi (intention-to-treat/safety population).. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to week 24 in the modified intention-to-treat population (study participants with HbA1c available at baseline and week 24). Secondary efficacy outcomes were percentage of participants reaching HbA1c targets and change in fasting plasma glucose (FPG).. Mean baseline HbA1c was 9.2% (SD 1.4) and FPG was 10.8 mmol/L (2.9). Mean HbA1c change was -1.3% (95% CI: -1.4% to -1.2%, p<0.0001) at week 24. HbA1c levels ≤6.5%, <7% and<7.5% at week 24 were achieved by 72 (8.9%), 183 (22.6%) and 342 (42.3%) participants, respectively. Mean FPG change was -3.1 mmol/L (95% CI: -3.3 to -2.8, p<0.001) at week 24. Mean body weight change was -1.6 kg (95% CI: -1.9 to -1.3, p<0.001) at 24 weeks. Mean iGlarLixi dose increased from 19.5 U (SD 7.7) and 30.1 U (10.0) to 30.2 U (8.9) (ratio 2/1 pen) and 45.0 U (11.6) (ratio 3/1 pen). Adverse events (AEs) were reported by 43 (4.9%) participants (18 (2.1%) gastrointestinal) with 4 (0.5%) reporting serious AEs. 13 (1.5%) participants reported at least one event of symptomatic hypoglycaemia, with one episode of severe hypoglycaemia reported.. In a real-world setting, 24-week treatment with iGlarLixi provided a significant reduction of HbA1c with body weight loss and low hypoglycaemia risk in T2D suboptimally controlled with OADs±BI treatment.

Topics: Adult; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Peptides; Prospective Studies; Romania

The patient was 82-year-old man with type 1 diabetes mellitus. He had been using insulin degludec (IDeg) and insulin glulisine (IGlu) for treatment. He was admitted to our hospital due to diabetic ketoacidosis. As he started eating after recovery, we restarted intensive insulin therapy for glycemic control. Although he had eaten almost whole meals, his fasting blood glucose was extremely low, and the existence of nocturnal hypoglycemia was apparent. We reduced the dose and changed the injection time (evening→morning) of IDeg. We also stopped the evening IGlu injection; however, his nocturnal hypoglycemia did not improve. We decided to switch IDeg to insulin glargine U300 and to attach an intermittently scanned continuous glucose monitor (isCGM). His nocturnal hypoglycemia improved three days later. Since he had chronic heart failure and premature ventricular contractions, we used a Holter electrocardiogram to investigate the difference in arrythmia during hypoglycemia and non-hypoglycemia. As a result, the number of premature ventricular contractions was apparently high during hypoglycemia. In the present case, which involved an elderly patient with type 1 diabetes mellitus, chronic heart failure and nocturnal hypoglycemia, switching IDeg to insulin glargine U300 improved nocturnal hypoglycemia. IDeg differs from insulin glargine U300 in that it has a fatty acid side chain, which leads IDeg to combine with serum albumin. We thought that the increased level of free fatty acid due to hypoglycemia was competing against albumin combined IDeg, which increased free IDeg, and as a result, encouraged hypoglycemia.

Topics: Aged; Aged, 80 and over; Chronic Disease; Diabetes Mellitus, Type 1; Heart Failure; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Ventricular Premature Complexes

This study assessed comparative effectiveness of glargine 300 U/mL (Gla-300) versus degludec 100 U/mL (Deg-100) in insulin-naïve patients with T2D.. This is a retrospective, multicenter, non-inferiority study based on electronic medical records. All patients initiating Gla-300 or Deg-100 were 1:1 propensity score-matched (PSM). Linear mixed models were used to assess the changes in continuous endpoints. Incidence rates (IR) of hypoglycemia were compared using Poisson's regression models.. Nineteen centers provided data on 357 patients in each PSM cohort. HbA1c after 6 months (primary endpoint) decreased by - 1.70% (95%CI - 1.90; - 1.50) in Gla-300 group and - 169% (95%CI - 1.89; - 1.49) in Deg-100 group, confirming non-inferiority of Gla-300 versus Deg-100. Fasting blood glucose (BG) decreased by ~60 mg/dl in both groups; body weight remained unchanged. In both groups, the mean starting dose was 12U (0.15U/kg) and it was slightly titrated to 16U (0.20U/kg). IR (episodes per patient-months) of BG ≤70 mg/dl was 0.13 in Gla-300 group and 0.14 in Deg-100 group (p=0.87). IR of BG <54 mg/dL was 0.02 in both groups (p=0.49). No severe hypoglycemia occurred.. Initiating Gla-300 or Deg-100 was associated with similar improvements in glycemic control, no weight gain and low hypoglycemia rates, without severe episodes during 6 months of treatment.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Retrospective Studies

Data on second generation basal insulin (2BI) in people with type 2 diabetes (T2D) generated by clinical trials still need confirmation in real-world clinical settings. This study aimed at assessing the comparative effectiveness of 2BI [Glargine 300 U/mL (Gla-300) vs. Degludec 100 U/mL (Deg-100)] in T2D Italian patients switching from first generation basal insulins (1BI).. This was a retrospective, non-inferiority, multicenter study. Patients switching to Gla-300 or Deg-100 from 1BI were 1:1 propensity score matched (PSM). Changes during 6 months in continuous endpoints were assessed through linear mixed models. Incidence rates (IR) of hypoglycemia (episodes per patient-months) were compared using Poisson regression. Each PSM cohort included 593 patients. HbA1c decreased from baseline (8.7%) to 6 months by -0.58% (95%CI -0.69;-0.47) in Gla-300 group and -0.50% (95%CI -0.61;-0.39) in Deg-100 group, confirming the non-inferiority of Gla-300 vs. Deg-100. No between-group differences emerged: FBG was reduced by about 20 mg/dl with both 2BI, mean dose of 2BI (24.5 U, 0.3 U/Kg at the first prescription) was suboptimally titrated during 6 months (+1.34 U in Gla-300 and + 1.76 U in Deg-100), body weight showed minor changes. IR of hypoglycemia <54 mg/dl was 0.32 (95%CI 0.21; 0.49) in Gla-300 group and 0.19 (95%CI 0.11; 0.33) in Deg-100 group (p = 0.14).. In subjects with T2D, switching to 2BI from 1BI was associated with similar improvements in glycemic control, low hypoglycemia rates and no weight gain in real-life setting. Clinical inertia, represented by late treatment intensification and suboptimal titration, represents a major issue in Italy.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Retrospective Studies

To assess patient-reported outcomes (PROs) in the SoliMix trial, which compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D).. SoliMix (EudraCT: 2017-003370-13), a 26-week, open-label study, randomized (1:1) 887 adults with T2D and HbA1c ≥7.5%-≤10.0% (≥58-≤86 mmol/mol) on basal insulin plus oral antihyperglycaemic drugs (OADs) to once-daily iGlarLixi or twice-daily premix insulin, BIAsp 30. PROs were assessed using the Treatment-Related Impact Measure Diabetes (TRIM-D) and Global Treatment Effectiveness Evaluation (GTEE) questionnaires.. Over 26 weeks, iGlarLixi showed greater improvement from baseline versus BIAsp 30 in total TRIM-D score (least squares mean difference [95% confidence interval]: 5.08 [3.69, 6.47]; effect size: 0.32) and in each TRIM-D domain, with the greatest differences seen in diabetes management (8.47 [6.11, 10.84]) and treatment burden (6.95 [4.83, 9.07]). GTEE scores showed a greater proportion of participants and physicians rated a complete or marked improvement of diabetes control with iGlarLixi (80.5%, 82.8%) versus BIAsp 30 (63.3%, 65.1%) at week 26. Post hoc analyses showed that after adjusting for HbA1c, body weight and hypoglycaemia outcomes, iGlarLixi continued to show greater improvements in TRIM-D total scores versus BIAsp 30.. In addition to better glycaemic control, weight benefit and less hypoglycaemia, once-daily iGlarLixi provided improved diabetes management, treatment burden and perceived effectiveness versus twice-daily premix BIAsp 30, further supporting iGlarLixi as an advanced treatment option in people with suboptimally controlled T2D on basal insulin plus OADs.

Topics: Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Patient Reported Outcome Measures; Treatment Outcome

With limited real-world insulin glargine 300 U/mL (Gla-300) data among Japanese patients with type 1 diabetes mellitus (T1DM) available, the authors describe its effectiveness and safety in Japanese T1DM patients switching to Gla-300.. X-STAR was a 12-month prospective, observational, post-marketing study in Japanese patients with diabetes mellitus from 2015 to 2018: insulin-experienced T1DM patients initiating Gla-300 were analyzed.. Of 774 patients, mean (±standard deviation) HbA1c (%) and fasting plasma glucose (mg/dL) decreased from 8.27 ± 1.55 to 8.15 ± 1.35 (by -0.12 ± 1.30 [p = 0.013]) and 167.9 ± 92.6 to 153.9 ± 70.9 (by -13.9 ± 103.8 [p = 0.067]) from baseline to month 12, respectively. A total of 16.3% achieved HbA1c <7.0% at month 12. Gla-300 dose increased by 1.13 ± 3.18 U/day (0.02 ± 0.05 U/kg/day) (p < 0.001), with a + 0.22 ± 2.70 (p = 0.037) body-weight change (kg) from baseline 60.83 ± 12.81 to 12-month 61.06 ± 12.89. Adverse drug reactions (ADRs) and serious ADRs occurred in 9.82% and 0.78% of the patients, respectively. Hypoglycemia was the most common ADR (9.30%). In total, 88.9% adhered to Gla-300 administration schedules, whereas <40% adhered to exercise and dietary instructions, respectively.. Gla-300 showed no unprecedented safety concerns for insulin-experienced T1DM patients in Japanese clinical settings. Our results provide insights into strategies for blunted Gla-300 up-titration dose, despite insufficient HbA1c control and lifestyle modification.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Middle Aged; Product Surveillance, Postmarketing; Prospective Studies

This study aimed to compare the rate of hypoglycemic events from all spontaneously reported adverse events (AEs) between insulin detemir and insulin degludec using the Korea Adverse Event Reporting System (KAERS) database.. We analyzed data on the reported hypoglycemia events retrieved from adverse drug reactions (ADR) on the use of different insulin types from 2016 to 2017 in the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). After defining hypoglycemic events as the AE of interest, we performed a disproportionality analysis by calculating the reporting odds ratio (ROR) to identify the disproportionality of AEs following treatment with insulin degludec (IDeg) and insulin detemir (IDet). Because spontaneously reported hypoglycemic events were not distinguished between insulin glargine 100 U/mL (Gla-100) and insulin glargine 300 U/mL (Gla-300) due to same ATC code by KIDS-KD, direct comparisons of Gla-100 and Gla-300 or comparisons of each analog of insulin glargine vs. IDet or IDeg, respectively, could not be achieved.. Of the 3,220 AEs caused by the use of long-acting basal insulin, 739 and 296 were caused by IDeg and IDet, respectively. Among these, 172 (23.3%) of the 739 and 83 (28.0%) of the 296 AEs were reported to be hypoglycemic events caused by IDeg and IDet, respectively. The rate of reported hypoglycemic events caused by IDeg was lower than that of IDet (ROR (95% CI): 0.78 (0.71 - 0.86)). Further, IDeg consistently caused lower hypoglycemia events than IDet in the sensitivity analysis (ROR (95% CI): 0.41 (0.37 - 0.46)).. When we compared the proportionality of hypoglycemic events among the total number of reported AEs for each of the two basal insulins through disproportionality analysis using the spontaneous ADR reporting system, IDeg showed a relatively lower rate of reported hypoglycemic events than IDet.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Republic of Korea

Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed the real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the United States, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2 and 3 (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs. insulin degludec) RCTs, we observed that only 17% (33 345/191 218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36 285/235 697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24 547) would have been eligible for the CONCLUDE (insulin degludec vs. Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Randomized Controlled Trials as Topic

This study investigated the hypoglycemia risk in people with type 2 diabetes (T2D) who initiated or switched to insulin glargine 300 U/mL (Gla-300) by stratifying them by age and renal function.. We examined data from 4621 people with T2D (1227 insulin-naïve and 3394 insulin-experienced) of the X-STAR study, a prospective, observational, 12-month study conducted from December 2015 to August 2018 in Japan. Participants were stratified by age (<65, 65 to <75, and ≥75 years) and estimated glomerular filtration rate (eGFR) (≥90, 60 to <90, 30 to <60, and <30 mL/min/1.73 m. No apparent increase in the proportion of people who experienced hypoglycemia was found in all subgroups. The proportions were 2.9-3.5% and 2.7-5.2% of insulin-naïve and insulin-experienced people, respectively, for age subgroups, and 2.4-4.7% and 4.6-4.8%, respectively, for eGFR subgroups. The result was similar for HbA1c levels below and at or above 7.0% in all age subgroups.. Our study found no apparent increase in the hypoglycemia risk in people with older age and renal impairment who were administered Gla-300. These results would provide reassuring information on Gla-300 use.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Middle Aged; Prospective Studies

Rosenstock J, Bajaj HS, Janež A, et al.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus insulin degludec 100 U/mL (IDeg-100) in predefined (

Topics: Adult; Aged; Blood Glucose; Child, Preschool; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Infant; Insulin Glargine; Insulin, Long-Acting

In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during the maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes. In this post hoc analysis, data from 7635 individuals from DEVOTE and 720 individuals from SWITCH 2 were analysed by subgroups of diabetes duration at baseline (<10, ≥10-<15, ≥15-<20 and ≥20 years) using prespecified models from both trials. There was a trend towards lower rates of hypoglycaemia with degludec versus glargine U100 across all diabetes duration subgroups in both trials, with the difference being statistically significant in some subgroups in DEVOTE and SWITCH 2. Overall, however, no significant interaction was observed between diabetes duration and treatment (DEVOTE interaction, P = .496; SWITCH 2 interaction, P = .144). Therefore, in this post hoc analysis of DEVOTE and SWITCH 2, diabetes duration did not appear to affect the reduction in rates of hypoglycaemia observed with degludec compared with glargine U100.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

Topics: Animals; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Macaca mulatta

To determine whether basal insulin analogs reduce the rate of composite neonatal morbidity compared with neutral protamine Hagedorn (NPH) in women with type 2 diabetes mellitus (T2DM).. This was a retrospective cohort study of women with T2DM and singleton pregnancy at a single tertiary center. Primary outcome was a composite neonatal morbidity of any of the following: shoulder dystocia, large for gestational age, neonatal intensive care unit admission, neonatal hypoglycemia, or respiratory distress syndrome. Secondary outcomes were rates of maternal hypoglycemic events, hypertensive disorders, preterm birth, and primary cesarean delivery. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated.. Of 233 women with T2DM that met the inclusion criteria, 114 (49%) were treated with basal insulin analogs and 119 (51%) with NPH. The rate of composite neonatal morbidity was similar between groups (73 vs. 60%; aRR: 1.18; 95% CI: 0.92-1.51). There were no differences in the rates of maternal adverse outcomes between the groups. Basal insulin analog was associated with a lower rate of primary cesarean delivery as compared with NPH (21 vs. 36%; aRR: 0.44; 95% CI: 0.25-0.78).. Among pregnant women with T2DM managed with either basal or NPH insulin regimen, the rates of composite neonatal morbidity and maternal complications were similar.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Infant, Newborn, Diseases; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Logistic Models; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Premature Birth; Retrospective Studies; Young Adult

To examine the relationship between baseline fasting C-peptide (FCP) and outcomes in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL (Gla-100).. Post hoc pooled analysis of nine randomized, treat-to-target trials in patients with type 2 diabetes inadequately controlled on oral antihyperglycaemic drugs initiating once-daily Gla-100. Participants (n = 2165) were stratified at baseline according to FCP (≤0.40, >0.40-1.20, >1.20-2.00, >2.00 nmol/L). Glycaemic control, body weight, insulin dose and hypoglycaemia were determined at 24 weeks.. At baseline low FCP levels were associated with longer known diabetes duration, lower body mass index and higher fasting plasma glucose (FPG). Following Gla-100 introduction, the mean HbA1c reduction at week 24 was similar in all four FCP groups, albeit fewer people in the lowest FCP group achieved HbA1c <7.0% versus FCP groups >0.40 nmol/L. By contrast, FPG reduction and proportion reaching FPG ≤5.6 mmol/L were greatest in the lowest FCP group, diminishing at higher FCP levels. Gla-100 dose at week 24 was lowest in the ≤0.40 nmol/L FCP group and highest in the >1.20 nmol/L FCP group. Incidence and event rate of overall, nocturnal and severe hypoglycaemia were higher at week 24 in groups with lower FCP levels. In multivariable regression analysis baseline FCP, concomitant sulphonylurea use and endpoint HbA1c were strong predictors of hypoglycaemia.. FCP levels identified patients with type 2 diabetes experiencing different responses to basal insulin Gla-100. A low FCP identifies a markedly insulin-deficient, insulin-sensitive subgroup/phenotype with an enhanced risk of hypoglycaemia, which requires a low initial basal insulin dose, cautious titration and earlier addition of prandial glucose-lowering therapy.

Topics: Biomarkers; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fasting; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

Real-world evidence of the safety of insulin degludec compared with insulin glargine U100 is sparse. This study sought to investigate the risk of major cardiovascular events, severe hypoglycaemia, and all-cause mortality after initiation of degludec or glargine U100 in the population of Denmark.. All Danish people with diabetes initiating treatment on degludec (n=5159) or glargine (n=4041) in 2016 to 2017 were included in the study. The effect of insulin treatment on the endpoints of major cardiovascular events, severe hypoglycaemia, and all-cause mortality was analysed with Cox proportional hazard models. The models were adjusted for age, sex, diabetes duration, diabetes type, highest completed education, and annual income. The model of severe hypoglycaemia was also adjusted for severe hypoglycaemia prior to baseline. The model of mortality was also adjusted for history of alcohol abuse, use of antidepressants, use of opioids, and use of anxiolytics. Lastly, the models of major cardiovascular events and mortality were also adjusted for Charlson comorbidity index.. Use of degludec resulted in an almost twofold decrease in risk of death (hazard rate [HR]: 0.54, 95% CI: 0.44-0.65) compared with use of glargine. No statistically significant risk changes were found for major cardiovascular events (HR: 0.86, 95% CI: 0.62-1.19) and severe hypoglycaemia (HR: 1.13, 95% CI: 0.66-1.93). The proportion of cause of death due to malignant neoplasm of pancreas was almost doubled for glargine compared with degludec.. These results indicate that insulin degludec has a safer profile with respect to all-cause mortality as compared with insulin glargine U100.

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cohort Studies; Denmark; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Prognosis; Risk Factors; Survival Rate

Treat-to-target, randomized controlled trials have confirmed lower rates of hypoglycaemia at equivalent glycaemic control with insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 1 (T1D) or type 2 diabetes (T2D). Treat-to-target trials are designed to enable comparisons of safety and tolerability at a similar HbA1c level. In this post hoc analysis of the SWITCH 1 and 2 trials, we utilised a patient-level modelling approach to compare how glycaemic control might differ between basal insulins at a similar rate of hypoglycaemia.. Data for HbA1c and symptomatic hypoglycaemia from the SWITCH 1 and SWITCH 2 trials were analyzed separately for patients with type 1 diabetes and type 2 diabetes, respectively. The association between the individual patient-level risk of hypoglycaemia and HbA1c was investigated using a Poisson regression model and used to estimate potential differences in glycaemic control with degludec versus glargine U100, at the same rate of hypoglycaemia.. Our findings suggest that patients in clinical practice may be able to achieve lower glycaemia targets with degludec versus glargine U100, before incurring an equivalent risk of hypoglycaemia.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Reproducibility of Results

Absztrakt: Az 1-es típusú diabetes mortalitása, bár csökkenő tendenciát mutatva, jelentősen meghaladja a standard mortalitást. Ez egyúttal a diabetesszel megélt életévek rövidülésével jár együtt. Az esetismertetés tárgya egy 86 éves diabetestartammal a 91. életévét megélő nőbeteg, akit több mint 55 éven keresztül egyetlen orvos – a szerző – kezelt/gondozott. Az 1932-ben, ötéves korában fellépett diabetest először naponta háromszor adagolt gyors hatású inzulinnal, majd 1940-től kezdve naponta egyszer alkalmazott gyors hatású és cink-protamin inzulinnal, később sertés, majd humán kristályos cinkinzulinnal, majd az utolsó 16 évben gyors hatású NPH-inzulin keverékével kezelték. Ennek oka az volt, hogy a beteg rögeszmésen ragaszkodott a napi egyszeri inzulinadáshoz, és hogy esetében mindegyik inzulin hatástartama 24 órásnak bizonyult. Az évtizedeken át folyamatosan túladagolt egyszeri inzulinadás következménye a szinte naponta, főként az éjjeli órákban fellépő hypoglykaemia lett, következményes nagyfokú vércukor-ingadozásokkal. Az 1930-as évek közepétől a hatvanas évekig polarimetriás, majd száraz kémiás módszerrel vizeletcukor-önellenőrzést végzett a nyolcvanas évek elejéig, majd áttért a vércukor-önellenőrzésre. Az ötvenes években két sikertelen terhessége volt, 2010–11-ben egymás után jobb, majd bal oldali combnyaktörést szenvedett, majd mindkét szemén megműtötték a cataractáját. Az utolsó 25 évben HbA

Topics: Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 1; Fatal Outcome; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Myocardial Infarction; Treatment Outcome

The aim is to devise a new short-term intensive insulin therapy (N-SIIT) based on the concept of "treat to target" to avoid hypoglycaemia and was applied it to various diabetic state. We determined dosage of 1 basal and 3 bolus "treat" insulin based on "target" blood glucose level and changed each insulin dose by small units (2 units) every day for 2 weeks. We evaluated the effects of N-SIIT in 74 subjects with type 2 diabetes (male 45, female 29, 64.9 ± 16.6 years old, HbA1c 10.4 ± 2.6%). Glargine U300 ("treat") and morning blood glucose level ("target") was significantly correlated with increasing insulin dose and decreasing blood glucose level in day 1-7, indicating that insulin amount was determined by target blood glucose level and lowered next target blood glucose level. Remission rates were 67.3% (Hypoglycaemia rate 5.6 %) in N-SIIT and 47.3% (Hypoglycaemia rate 38.1%) in conventional SIIT. Required amount of insulin would be automatically determined, depending on each patient pathophysiology and life style. This method is pretty simple, flexible and cheap, and provides information about the dynamic pathophysiological alteration of insulin resistance and glucotoxicity from the profile of blood glucose levels and insulin shot.

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Life Style; Male; Middle Aged; Practice Guidelines as Topic

To undertake a post-hoc analysis, utilizing a hypoglycaemia risk score based on DEVOTE trial data, to investigate if a high risk of severe hypoglycaemia was associated with an increased risk of cardiovascular events, and whether reduced rates of severe hypoglycaemia in patients identified as having the highest risk affected the risk of cardiovascular outcomes.. The DEVOTE population was divided into quartiles according to patients' individual hypoglycaemia risk scores. For each quartile, the observed incidence and rate of severe hypoglycaemia, major adverse cardiovascular event (MACE) and all-cause mortality were determined to investigate whether those with the highest risk of hypoglycaemia were also at the greatest risk of MACE and all-cause mortality. In addition, treatment differences within each risk quartile [insulin degludec (degludec) vs. insulin glargine 100 units/mL (glargine U100)] in terms of severe hypoglycaemia, MACE and all-cause mortality were investigated.. Patients with the highest risk scores had the highest rates of severe hypoglycaemia, MACE and all-cause mortality. Treatment ratios between degludec and glargine U100 in the highest risk quartile were 95% confidence interval (CI) 0.56 (0.39; 0.80) (severe hypoglycaemia), 95% CI 0.76 (0.58; 0.99) (MACE) and 95% CI 0.77 (0.55; 1.07) (all-cause mortality).. The risk score demonstrated that a high risk of severe hypoglycaemia was associated with a high incidence of MACE and all-cause mortality and that, in this high-risk group, those treated with degludec had a lower incidence of MACE. These observations support the hypothesis that hypoglycaemia is a risk factor for cardiovascular events.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

The relationship between baseline fasting C-peptide (FCP) and glucose control was examined in insulin-naïve people with type 2 diabetes inadequately controlled with oral antihyperglycaemic drugs commencing basal insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) in the absence of sulfonylurea/glinides. Participants with FCP measurement from the EDITION 3 trial (n = 867) were stratified according to baseline FCP (≤0.40, >0.40-1.20, >1.20 nmol/L); 11.0%, 70.9% and 18.1% contributed to each group. Glycaemic control, body weight, insulin dose and hypoglycaemia were determined at 26 weeks. Glycaemic control (HbA1c, FPG) at 26 weeks was similar in each FCP group between insulins. However, end-of-study insulin dose was greater with higher FCP for both insulins. More people with lower baseline FCP experienced hypoglycaemia with both insulins, but with numerically lower incidence for Gla-300 versus Gla-100 across all FCP groups for all definitions (time periods and levels) of hypoglycaemia. This suggests that Gla-300 might be particularly advantageous for people who are at higher risk of hypoglycaemia.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

ORION evaluated the safety and effectiveness of Gla-300 in insulin-treated people with T2DM before, during and after Ramadan, in a real-world setting.. This prospective, observational study across 11 countries included participants with T2DM treated with Gla-300 in pre-Ramadan, Ramadan and post-Ramadan periods. The primary endpoint was the percentage of participants experiencing ≥1 event of severe and/or symptomatic documented hypoglycaemia with self-monitored plasma glucose (SMPG) ≤70 mg/dL during Ramadan. Secondary endpoints included change in HbA. In ORION, people with T2DM treated with Gla-300 who fasted during Ramadan had a low risk of severe/symptomatic hypoglycaemia and improved glycaemic control.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Islam; Male; Middle Aged; Religion and Medicine; Treatment Outcome

To explore the glucagon-like peptide-1 analogue liraglutide in the hospital setting in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome and to evaluate the safety and efficacy and its impact on hospitalization and short-term glycemic variability (GV).. A 12-week, open-label, prospective, randomized pilot clinical study with parallel groups that compared liraglutide (group 1) with glargine (group 2) and its impact on glycemic control and GV.. Thirteen patients were included. During hospitalization, mean glucose was 164.75 mg/dL (standard deviation [SD] 19.94) in group 1 and 166.69 mg/dL (38.22) in group 2. GV determined by CV and SD was 20.98 (7.68) vs. 25.48 (7.19) and 34.37 (13.05) vs. 43.56 (19.53) in groups 1 and 2, respectively. Group 1 prandial insulin requirements during hospitalization were lower compared with group 2. Follow-up A1c in group 1 was 6.9% (-1.51%) and 6.5% in group 2 (-1.27). GV after discharge and hypoglycemia were lower in group 1 compared with group 2.. Liraglutide seems to reduce GV in the acute phase of acute coronary syndrome, and patients achieved optimal control with a low incidence of hypoglycemia. These results support the need to explore liraglutide in a larger multicenter trial.

Topics: Acute Coronary Syndrome; Adult; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Glycemic Index; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Liraglutide; Male; Metformin; Middle Aged; Pilot Projects; Random Allocation; Spain

Randomized controlled trials and real-world data from the USA have shown similar glycemic control with insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) and reduced hypoglycemia risk with Gla-300. This real-world study describes the efficacy and safety of Gla-300 and Gla-100 in patients with type 2 diabetes (T2D) in France, Spain, and Germany.. This retrospective chart review analysis used anonymized data for adults with T2D switching basal insulin analog (BIA) therapy to Gla-300 or Gla-100, or insulin-naïve patients initiating Gla-300 or Gla-100. Outcomes included change from baseline to 6-month follow-up in glycated hemoglobin A1c (A1C), total and severe hypoglycemia incidences and events, insulin dose, and reasons for BIA choice.. Six hundred sixty-five physicians (33.8% Spain, 31.7% France, 34.4% Germany) provided chart data for patients switching to Gla-300 (n = 679) or Gla-100 (n = 429) or initiating Gla-300 (n = 719) or Gla-100 (n = 711). After adjustment for baseline characteristics, A1C reductions from baseline were similar for patients switching to Gla-300 or Gla-100 (- 0.87% vs. - 0.93%; p = 0.326) while those switched to Gla-300 vs. Gla-100 had a significantly greater mean reduction in hypoglycemic events (- 1.29 vs. - 0.81 events during 6 months; p = 0.012). Mean insulin doses after titration were 0.43 ± 0.36 and 0.40 ± 0.28 U/kg in Gla-300 and Gla-100 switchers, respectively. Factors that significantly influenced BIA choice included a lower risk of hypoglycemia (for Gla-300) and physician familiarity (for Gla-100). Outcomes for insulin-naïve patients were broadly similar to those of switchers.. In this real-world European study, patients with T2D who switched therapy to Gla-300 or Gla-100 had improved glycemic control and reduced hypoglycemia at 6 months, with significant hypoglycemia advantages with Gla-300.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; France; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Male; Middle Aged; Retrospective Studies; Spain; Treatment Outcome

With limited real-world insulin glargine 300 unit/mL (Gla-300) data available, we assessed the effectiveness and safety of Gla-300 in the Japanese type 2 diabetes mellitus (T2DM) population.. X-STAR was a prospective, observational, 12-month post-marketing study of Gla-300 from 2015 to 2018. T2DM patients received Gla-300 as the first insulin (insulin-naïve) or after treatment with another type of insulin (insulin-experienced).. We identified 1,227 insulin-naïve and 3,394 insulin-experienced patients. Insulin-naïve group increased the Gla-300 starting dose by 2.80 U/day during 12 months (7.49 to 10.29 U/day). Mean HbA1c reduced by 1.99% (9.82 to 7.83%), and 28.4% showed HbA1c < 7.0%. Insulin-experienced group had a baseline insulin dose of 14.86 U/day, which increased by 0.73 U/day. Mean HbA1c reduced by 0.18% (7.99 to 7.81%), and 24.6% showed HbA1c < 7.0%. Adverse drug reactions occurred in 3.42% (insulin-naïve) and 4.45% (insulin-experienced); symptomatic hypoglycemia (2.93% and 3.86%, respectively) was the most common in both groups.. Gla-300, in clinical practice, provides an effective and safe therapy as HbA1c was reduced/maintained in insulin-naïve/experienced Japanese T2DM patients without new safety signal. This study provides insights into the current Japanese clinical practices where insulin use is delayed and conservative despite relatively low HbA1c achievement.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Japan; Male; Middle Aged; Product Surveillance, Postmarketing; Prospective Studies; Treatment Outcome

The ability to differentiate patient populations with type 2 diabetes at high risk of severe hypoglycaemia could impact clinical decision making. The aim of this study was to develop a risk score, using patient characteristics, that could differentiate between populations with higher and lower 2-year risk of severe hypoglycaemia among individuals at increased risk of cardiovascular disease.. Two models were developed for the risk score based on data from the DEVOTE cardiovascular outcomes trials. The first, a data-driven machine-learning model, used stepwise regression with bidirectional elimination to identify risk factors for severe hypoglycaemia. The second, a risk score based on known clinical risk factors accessible in clinical practice identified from the data-driven model, included: insulin treatment regimen; diabetes duration; sex; age; and glycated haemoglobin, all at baseline. Both the data-driven model and simple risk score were evaluated for discrimination, calibration and generalizability using data from DEVOTE, and were validated against the external LEADER cardiovascular outcomes trial dataset.. Both the data-driven model and the simple risk score discriminated between patients at higher and lower hypoglycaemia risk, and performed similarly well based on the time-dependent area under the curve index (0.63 and 0.66, respectively) over a 2-year time horizon.. Both the data-driven model and the simple hypoglycaemia risk score were able to discriminate between patients at higher and lower risk of severe hypoglycaemia, the latter doing so using easily accessible clinical data. The implementation of such a tool (http://www.hyporiskscore.com/) may facilitate improved recognition of, and education about, severe hypoglycaemia risk, potentially improving patient care.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Risk Factors

To evaluate insulin treatment satisfaction, safety, and effectiveness of biosimilar insulin glargine (GLY) in real-world clinical practice for Japanese patients with type 2 diabetes mellitus (T2DM) who switched from originator insulin glargine (100 U/mL) or insulin degludec treatment to GLY treatment.. The Insulin Treatment Satisfaction Questionnaire (ITSQ) was used to assess treatment satisfaction in a subgroup analysis of a post-marketing safety study. Hypoglycemia incidence rates and blood glucose control are also reported during the 12-month observation period for GLY-switched patients.. Of 1104 patients with T2DM enrolled to participate, 565 patients switched from either insulin glargine U100/mL (. Treatment satisfaction does not change significantly in Japanese patients with T2DM who switch to GLY from the reference product or from insulin degludec. Safety and effectiveness over a 12-month period were similar in GLY-treated patients who switched from either insulin glargine or insulin degludec.. Not applicable.

Topics: Adult; Aged; Aged, 80 and over; Biosimilar Pharmaceuticals; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Product Surveillance, Postmarketing; Prospective Studies; Surveys and Questionnaires

Early insulin initiation benefits people with diabetes by inducing a rapid and sustained glycemic control along with preventing the onset of adverse legacy effects early in the disease course. This has an over-arching effect as it could possibly modify the disease course and prevent the development of vascular complications, as has been attested to in landmark studies like the UKPDS and GRACE. Insulin glargine 100 U/mL (Gla-100) has been extensively studied under various scenarios as the initial insulin administered early in T2DM disease course, registering significant glycemic and vascular benefits over the standard of care. By virtue of its ease of use and better safety profile, basal insulin like Gla-100 has been recommended by various international and Indian guidelines as the go-to initial insulin in people with diabetes. Further, the ability to personalize the initiating dose basis one's HbA1c and weight is an additional feature that contributes to the scientific merit of initiating with basal insulin like Gla-100. However, early insulin initiation is mostly delayed owing to 'clinical inertia,' thereby causing an evitable glycemic burden. Therefore, physicians managing diabetes must aim to increase acceptance, persistence, and adherence to insulin therapy by focusing on the safety, simplicity, and convenience of therapies.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine

The inadequate control of postprandial glucose (PPG) excursions, are linked in some studies with cardiovascular disease. Even though basal insulins, such as insulin glargine 100 U/mL (Gla-100), maintain overall glycemic control, effective PPG control eventually requires intensification of therapy by adding prandial insulins. Compared to conventional basal-bolus or premixed approaches, a stepwise basal-plus or basal-prandial intensification regimen involving the addition of one, two, or three prandial insulins to basal therapy such as Gla-100, has received much attention in recent times. This intensification approach is comparable to other conventional approaches in terms of glycemic control, and offers the additional advantages of fewer hypoglycemic events, personalization of therapy, and a simple self-management algorithm for titration. Owing to such benefits, recent guidelines recommend its use over other approaches for initiating intensification. It is preferred by both physicians and patients and is a better alternative to immediately embarking on a full basal-bolus regimen or introducing premixed insulin preparations for intensification of therapy.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulins

Both hyperglycemia and hypoglycemia in hospitalized patients represent a major concern as they are associated with adverse outcomes-including increased rates of infection, longer hospital stay, and even death. Insulin therapy is the mainstay in the management of inpatient hyperglycemia. The traditional approach of sliding scale insulin (SSI) therapy for the temporary management of blood glucose levels in hospitalized patients, has now given way to basal-bolus insulin (BBI) therapy. This is owing to the BBI affording a better glycemic control in non-critical hospital settings as observed in multiple clinical studies using insulin glargine 100 U/mL (Gla-100) as the basal component. Furthermore, a string of clinical studies has also attested to Gla-100 being used effectively even in patients on corticosteroids, enteral or parenteral nutrition, and in perioperative settings. Hence, overall, the existing evidence would point to the growing role of BBI regimens centering around basal insulin like Gla-100 as an effective option with low safety concerns for insulin therapy in both hospitalized and out-patient settings in the treatment of patients with type 2 diabetes mellitus (T2DM).

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

Despite the benefits and clinical necessity of insulin treatment in type 2 diabetes (T2D), healthcare providers are reluctant to initiate insulin, and patients are reluctant to start it for several reasons, one of these being the complexity of insulin treatment. Patients and their healthcare providers can benefit from titration algorithms (TAs) or rules that assist with the initiation and titration of insulin, performing the calculations that are needed to safely initiate and conservatively adjust.. The primary objective for this in silico study was to examine the effectiveness of 3 dose TAs (1-3) for optimization of basal insulin glargine (Gla-100 and Gla-300). In the simulations, 100 virtual subjects with T2D were included (50% men, age 62 ± 3 years, HbA1c 8.1% ± 2.9%, body weight 94 ± 16 kg). Subjects were studied under each TA (TA1 and TA2 fasting blood glucose [FBG] targets 90-130 mg/dL, TA3 FBG target 110-150 mg/dL). Initial dose of both insulins was based on 0.2 U/kg body weight. During 3 months, subjects reported their FBG to the LTHome web-based dose guidance system with a rules engine to safely guide long-acting insulin titration and maintenance. Subjects followed dose recommendations to reach designated FBG target ranges.. All subjects reached stable doses under all TAs with both Gla-100 and Gla-300 insulin, and 93 or more of the 100 subjects, depending on the assigned TA, achieved the target FBG range within the 3-month simulation for all TAs. Mean FBG was lowered (Gla-100: 155 ± 40 to 118 ± 11 mg/dL with TA1 and TA2 and 132 ± 12 mg/dL for TA3; Gla-300: 125 ± 14 with TA1 and TA2 and 134 ± 15 mg/dL with TA3). Calculated HbA1c improved from 8.1% ± 2.9% to 7.1% ± 2.5% for TA1 and TA2 and 7.5% ± 2.5% for TA3, a reduction of 0.9% and 0.6% over 3 months for both insulins. Three subjects on Gla-100 and one subject on Gla-300 experienced mild hypoglycemia.. All TAs delivered safe dose recommendations with minimal hypoglycemia, leading to a stable glucose control in the majority of subjects.

Topics: Aged; Algorithms; Biomarkers; Blood Glucose; Computer Simulation; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Models, Biological; Time Factors; Treatment Outcome

Adequate insulin titration is crucial for optimal glycaemic control in type 2 diabetes (T2D). We aimed to explore the factors and outcomes associated with titration of glargine 100 U/mL (Gla-100) in patients uncontrolled on oral antidiabetic drugs (OAD) and initiating insulin therapy.. Patients from the Titration and Optimization (TOP)-1 registry were stratified by the magnitude of Gla-100 up-titration during the first month (no [< 1 Units (U)/day (d)], minimal [≥ 1 and < 5 U/d], moderate [≥ 5 and ≤ 8 U/d] and strong [> 8 U/d]). The primary endpoint was a fasting blood glucose (FBG) ≤ 110 mg/dL on ≥ 2 occasions and/or individual HbA1c target by 12 months.. Of 2308 patients, 905, 715, 409 and 279 underwent no, minimal, moderate and strong titration, respectively. Age decreased across increasing titration groups (p = 0.02) while body mass index (BMI) (p < 0.0001), FBG (p < 0.0001), and HbA1c (p < 0.0001) increased. At 12 months, the proportions of patients achieving the primary endpoint were comparable across groups (66.1% overall), though a smaller proportion of no titration patients met both their individual HbA1c target and FBG ≤ 110 mg/dL compared to moderate and strong titration patients (20.1% vs. 27.2% and 26.2%, p = 0.033 and 0.023, respectively). HbA1c was also comparable, though FBG was higher in the no titration group (126.2 vs. 122.6, 121.5 and 120.9 mg/dL, p < 0.02). A similar, small reduction in body weight occurred in all groups; hypoglycaemia rates were comparable across groups.. In real-world, titration of Gla-100 during the first month appears to coincide with a number of baseline factors. Insulin dose to meet HbA1c and FBG targets remains suboptimal in the majority of T2D patients.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Registries; Young Adult

To minimize the influence of possible confounding factors, the study was carried out in a cross-over manner. Using flash glucose monitoring, insulin glargine 300 U/mL showed less nocturnal hypoglycemia than insulin degludec 100 U/mL . Examination of insulin degludec 100 U/mL nocturnal hypoglycemia by combined oral medications suggested that metformin combination might be the cause of nocturnal hypoglycemia.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Insulins

To investigate the association between day-to-day fasting self-monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and to compare day-to-day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100).. Data were retrieved from two double-blind, randomized, treat-to-target, two-period (32 weeks each) crossover trials of degludec vs glargine U100 in T1D (SWITCH 1, n = 501) and T2D (SWITCH 2, n = 720). Available fasting SMBGs were used to determine the standard deviation (SD) of day-to-day fasting SMBG variability for each patient and the treatment combination. The association between day-to-day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, with fasting SMBG variability included as a three-level factor defined by population tertiles. Finally, day-to-day fasting SMBG variability was compared between treatments.. Linear regression showed that day-to-day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic and severe hypoglycaemia risk in T1D and T2D (P < 0.05). Day-to-day fasting SMBG variability was significantly associated (P < 0.01) with all categories of hypoglycaemia risk, with the exception of severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day-to-day fasting SMBG variability than glargine U100 in T1D (P = 0.0082) and with 10% lower day-to-day fasting SMBG variability in T2D (P < 0.0001).. Higher day-to-day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day-to-day fasting SMBG variability vs glargine U100.

Topics: Adolescent; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Female; Humans; Hypoglycemia; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Young Adult

To compare the real-world effectiveness of insulin degludec (degludec) and glargine 300 units/mL (glargine U300) in insulin-naïve adult patients with type 2 diabetes in routine US clinical practice.. CONFIRM is a non-interventional comparative effectiveness study following US patients across the continuum of care, through electronic medical records from multiple health systems and integrated delivery networks. Propensity-score matching controlled for confounding. The primary endpoint, change in HbA1c from baseline to 180 days of follow-up, was estimated using a repeated-measure of covariance analysis with subject as random effect. Change in the rate of hypoglycaemic episodes (defined using International Classification of Diseases codes 9/10) and change in proportion of patients with hypoglycaemia were estimated using negative binomial and logistic regression, respectively. Time-to-discontinuation of the initial basal insulin/initiation with another prescribed basal insulin was analysed using a Cox Proportional Hazard model.. Data concerning 4056 patients were analysed. After matching, baseline characteristics were comparable (n = 2028 in each group). After 180 days of follow-up, degludec was associated with a larger reduction in HbA1c (estimated treatment difference, -0.27%; P = 0.03), greater reductions in change in rate (rate ratio, 0.70; P < 0.05) and greater reductions in change in the likelihood of hypoglycaemia (odds ratio, 0.64; P < 0.01]) compared with glargine U300. In addition, patients treated with degludec were 27% less likely to discontinue treatment at follow-up compared with those treated with glargine U300 (hazard ratio, 0.73; P < 0.001).. Significantly improved HbA1c, larger reductions in rates and likelihood of hypoglycaemia and lower risk of treatment discontinuation were demonstrated with degludec vs glargine U300.

Topics: Adult; Aged; Blood Glucose; Comparative Effectiveness Research; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Medication Adherence; Middle Aged; Treatment Outcome

Current treatment of type 1 diabetes mellitus (T1DM) does not always achieve metabolic control because, among other things, the ocurrence of hypoglycemic events associated to insulin use.. A descriptive real life study of 247 T1DM patients, 55.5% male, aged 46.53 ± 16.23 years, and with a mean diabetes duration of 21.89 ± 11.99 years, who were switched from basal insulin glargine U100 to glargine U300. The primary endpoints were changes in Hba1c and number of hypoglycemic events, while secondary endpoints included changes in weight and insulin dose after 6 and 12 months.. After one year, no changes were seen in HbA1c, but the proportion of patients with HbA1c values <7.5% increased at 6 months (33.5 vs. 40.5%; P<0.05) and remained stable during one year of follow-up. Hypoglycemic events significantly decreased after one year of treatment in patients with previous hypoglycemic events. No changes were seen in body weight. Total insulin dose (U/kg) increased 7.24% at 6 months of treatment and by 8.69% at one year, mainly due to basal insulin. No changes were seen between the doses given at 6 and 12 months. These changes were similar in the different metabolic control groups and in patients with or without hypoglycemia. This increase was not related with prior basal insulin dose, baseline HbA1c level, number of hypoglycemic events or baseline weight.. Glargine U300 is a good basal insulin alternative to treat T1DM, improving metabolic control in patients with HbA1c levels >7,5 and decreasing hypoglycemic events in patients with history of hypoglycemia without increasing body weight.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Weight; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Substitution; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

To compare the effectiveness of different titration algorithms for insulin glargine U100 used in everyday practice to achieve glycaemic targets in patients with type 2 diabetes mellitus (T2DM).. A total of 526 patients (278 in Slovenia, 248 in Croatia) with T2DM (aged ≥ 18 years) and treated with insulin glargine prior to inclusion were enrolled. Patients self-titrated insulin glargine according to physicians' guidance.. Among the 524 patients included in the final analysis, the titration algorithm from the LANMET study was used most commonly (n = 368, 70.5% patients), followed by the Treat-To-Target (TTT) algorithm (n = 117, 22.4%). At the end of the study (6 months), 179 (34.3%) patients reached HbA1c ≤ 7%. There was no significant difference in the proportion of patients who reached their target HbA1c between the different algorithms at 6 months (35.6% using LANMET, 30.7% with TTT, and 32.4% with other algorithms; p = 0.611). HbA1c levels were more significantly reduced in patients using the TTT algorithm compared to LANMET (-2.31%, vs. -1.57%; p < 0.05). The proportion of patients with reported symptomatic hypoglycaemia did not differ significantly between the algorithms.. Continuous titration of insulin glargine U100 is a safe and efficient option for T2DM management, regardless of the titration algorithm applied.

Topics: Adolescent; Adult; Algorithms; Blood Glucose; Croatia; Diabetes Mellitus, Type 2; Diagnostic Tests, Routine; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Slovenia; Young Adult

Suliqua® (iGlarLixi) is a fixed ratio combination of basal insulin glargine U100 and the glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide. Both molecules exert complementary antihyperglycaemic effects : insulin glargine mainly targets fasting glycaemia while lixisenatide mainly targets postprandial hyperglycaemia. Thus, iGlarLixi is associated with a greater reduction in glycated haemoglobin (HbA1c) than each individual component and thereby results in a greater percentage of patients reaching HbA1c ? 7 %. It has a good tolerance profile, with a more favourable effect on body weight compared with insulin glargine alone and less gastrointestinal adverse effects when compared with lixisenatide alone, because of a more progressive titration of the GLP-1 receptor agonist component. iGlarLixi (Suliqua®) is presented as two different prefilled pens, one allowing to titrate glargine up to 40 IU/day, the other up to 60 IU/day, both with lixisenatide uptitrated to a maximum of 20 µg/day. This dual presentation facilitates a personalized approach according to patient's needs. Suliqua® is currently reimbursed, under conditions, for the management of type 2 diabetes not well controlled with basal insulin associated or not with oral antidiabetic agents.. Le Suliqua® (iGlarLixi) est une combinaison, à ratio fixe, de l’insuline basale glargine U100 et d’un agoniste du récepteur du glucagon-like peptide-1 (GLP-1), le lixisénatide. Les deux molécules exercent des effets antihyperglycémiants complémentaires : l’insuline glargine cible, principalement, la glycémie à jeun tandis que le lixisénatide cible, avant tout, la glycémie post-prandiale. Ainsi, la combinaison d’insuline glargine et de lixisénatide (iGlarLixi) entraîne une réduction plus importante du taux d’hémoglobine glyquée (HbA1c) que chaque composant individuel et permet d’atteindre plus souvent une cible d’HbA1c inf�rieur a 7 %. Elle offre également un bon profil de tolérance, avec un effet plus favorable sur le poids corporel par comparaison à l’insuline glargine seule et moins de manifestations indésirables digestives par rapport au lixisénatide seul et ce, grâce à une titration plus progressive du composant agoniste du récepteur du GLP-1. iGlarLixi (Suliqua®) est présenté sous forme de deux stylos pré-remplis, l’un permettant de titrer l’insuline glargine jusque 40 UI/jour, l’autre jusque 60 UI/jour, avec, dans les deux cas, une dose de lixisénatide allant jusqu’à un maximum de 20 µg. Ces deux présentations permettent au clinicien de mieux personnaliser l’approche thérapeutique en fonction des besoins du patient. Suliqua® est actuellement remboursé, sous conditions, dans le traitement du DT2 insuffisamment contrôlé sous insuline basale associée ou non à des antidiabétiques oraux.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Peptides

To compare HbA1c and hypoglycaemia in insulin-naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla-300) or 100 units/mL (Gla-100).. This retrospective cohort study examined electronic medical records of insulin-naïve adults with T2D who initiated Gla-300 or Gla-100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6-month baseline and 90-180-day follow-up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score-matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria.. The matched cohorts included 1004 Gla-300 and 2008 Gla-100 initiators (mean age 60.4 years; 53.2% male). During 6-month follow-up, Gla-300 versus Gla-100 initiators had a greater mean HbA1c decrease (-1.52 ± 2.08% vs. -1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla-300 initiators were similarly or less likely to have any or inpatient/emergency department-associated hypoglycaemia during 3- and 6-month follow-up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057).. Among insulin-naïve adults with T2D, Gla-300 was associated with significantly better HbA1c reductions (latest value during 90-180-day follow-up) and similar or improved hypoglycaemia outcomes (3- and 6-month follow-up) than Gla-100.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Retrospective Studies

Comparisons between brand and biosimilar basal insulin in hospitalized patients are lacking. We aimed to compare the efficacy and safety of brand insulin glargine vs. biosimilar insulin glargine in non-critical hospitalized patients with type 2 diabetes mellitus (T2DM).. This retrospective study was conducted using the electronic medical records of 194,006 patients at the Qingdao Endocrine and Diabetes Hospital between January 2006 and December 2017. A total of 476 patients diagnosed with T2DM, hospitalized, and treated with subcutaneous insulin glargine were included. After propensity score matching (1:3), patients who received biosimilar insulin glargine (Basalin) (n = 34) were compared to a matched group of patients who received brand insulin glargine (Lantus) (n = 101). Outcome measures were changes in fasting blood glucose (FBG), the incidence of hypoglycemia, and insulin dose.. Compared to patients who received Basalin, patients who received Lantus achieved more reduction in FBG during insulin treatment (- 1.24 mmol/L vs. - 2.20 mmol/L; p = 0.04) and had a lower mean FBG at the end of treatment (8.20 mmol/L vs. 7.26 mmol/L; p = 0.12). Patients in Basalin and Lantus groups had a comparable mean daily dose of basal insulin at initiation (0.19 vs. 0.18 IU/kg; p = 0.30) and end of treatment (0.21 vs. 0.21 IU/kg; p = 0.99), and a similar duration of basal insulin treatment (16.4 vs. 15.3 days; p = 0.74). Hypoglycemia was infrequent in both Basalin and Lantus treatment (one vs. four patients, respectively; p = 1.00) and no severe hypoglycemic events were reported.. In a non-critical hospital setting, subcutaneous treatment with Lantus brought significant FBG improvement without increased hypoglycemic risk.

Topics: Biosimilar Pharmaceuticals; Blood Glucose; China; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Outcome and Process Assessment, Health Care; Propensity Score; Retrospective Studies

Many youth with diabetes struggle to meet glycemic targets. The new ultralong duration of action of insulin degludec (iDeg) holds potential to ameliorate missed doses of basal insulin and improve glycemic control in youth with diabetes.. A retrospective chart review was undertaken of youth age 13 to <24 years in our practice with type 1 diabetes (T1D) or type 2 diabetes (T2D) who had been switched from glargine or detemir to iDeg to evaluate the impact of this transition on glycemic control.. Glycated hemoglobin A1c (HbA1c) in youth with T1D (n = 82) remained stable during 6 months of treatment with iDeg (10.1 ± 2.11% [87 ± 23 mmol/mol] at start of iDeg compared to 10.1 ± 2.12% [87 ± 23 mmol/mol] at 6 months of treatment), whereas in youth with T2D (n = 16), HbA1c significantly declined from 10.6 ± 2.3% (92 ± 25 mmol/mol) to 8.3 ± 2.2% (67 ± 24 mmol/mol) ( P = .0024).. In youth switched to iDeg, which in our practice is commonly due to ineffectiveness of the patient's current regimen, the outcome differences we saw may be due to preserved beta-cell function in youth with T2D. It remains to be seen whether there are benefits of transition to iDeg in youth with T1D beyond glycemic outcomes, such as reduction in ketosis and episodes of diabetic ketoacidosis.. DKA = diabetic ketoacidosis; DPV = Diabetes-Patienten-Verlaufsdokumentation (German/Austrian Prospective Diabetes Follow-Up Registry); HbA1c = glycated hemoglobin A1c; iDeg = insulin degludec; T1D = type 1 diabetes; T2D = type 2 diabetes.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Prospective Studies; Retrospective Studies

To evaluate the short-term cost-effectiveness of insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) from a Canadian public healthcare payer perspective in patients with type 2 diabetes (T2D) who are at high risk of cardiovascular events and hypoglycaemia.. A decision analytic model was developed to estimate costs (2017 Canadian dollars [CAD]) and clinical outcomes (quality-adjusted life years [QALYs]) with degludec vs glargine U100 over a 2-year time horizon. The model captured first major adverse cardiovascular event, death, severe hypoglycaemia and insulin dosing. Clinical outcomes were informed by a post hoc subgroup analysis of the DEVOTE trial (NCT01959529), which compared the cardiovascular safety of degludec and glargine U100 in patients with T2D who are at high cardiovascular risk. High hypoglycaemia risk was defined as the top quartile of patients (n = 1887) based on an index of baseline hypoglycaemia risk factors.. In patients at high hypoglycaemia risk, degludec was associated with mean cost savings (CAD 129 per patient) relative to glargine U100, driven by a lower incidence of non-fatal myocardial infarction, non-fatal stroke and severe hypoglycaemia, which offset the slightly higher cost of treatment with degludec. A reduced risk of cardiovascular death and severe hypoglycaemia resulted in improved effectiveness (+0.0132 QALYs) with degludec relative to glargine U100. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes.. Over a 2-year period, degludec improved clinical outcomes at a lower cost as compared to glargine U100 in patients with T2D at high risk of cardiovascular events and hypoglycaemia.

Topics: Aged; Canada; Cardiovascular Diseases; Cost Savings; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

Insulin degludec (Tresiba®) is characterized by an original mode of prolonged and continuous insulin release after its subcutaneous injection. Thereby, it has a very long glucose-lowering effect, around 42 hours, and a better reproducibility from both a pharmacokinetic and pharmacodynamic point of view. Its efficacy and safety have been assessed in the phase 3 clinical programme BEGIN as compared with insulin glargine U100, in patients with type 1 diabetes (T1D) and type 2 (T2D). For a similar glucose control (reduction in glycated haemoglobin), less hypoglycaemic episodes were recorded, including severe hypoglycaemia, during the nocturnal period, with insulin degludec than with insulin glargine U100. This clinical benefit has been confirmed in the complementary SWITCH programme in T1D and T2D patients at higher risk of hypoglycaemia, in the double-blind cardiovascular outcome trial DEVOTE in T2D patients at high cardiovascular risk and in real-life conditions in the observational European EU-TREAT study in patients with T1D and T2D. Insulin degludec (Tresiba®) is indicated and reimbursed for the treatment of patients with T1D, combined with a prandial insulin, and T2D, alone or combined with oral antidiabetic agents, a glucagon-like peptide-1 receptor agonist or a short-acting insulin.. L’insuline dégludec (Tresiba®) présente un mode original de libération prolongée et continue d’insuline, ce qui lui confère une durée d’action ultra-longue, avoisinant 42 heures, et une plus grande reproductibilité, à la fois sur le plan pharmacocinétique et pharmacodynamique. Son efficacité et sa sécurité d’emploi ont été validées dans le programme d’essais cliniques de phase 3 BEGIN en comparaison à l’insuline glargine U100, aussi bien dans le diabète de type 1 (DT1) que de type 2 (DT2). Pour un même niveau de contrôle glycémique (attesté par la réduction du taux d’hémoglobine glyquée), il y a eu moins d’hypoglycémies, y compris sévères, durant la période nocturne, avec l’insuline dégludec qu’avec l’insuline glargine U100. Ce bénéfice a été confirmé dans le programme complémentaire SWITCH chez des patients DT1 et DT2 à plus haut risque hypoglycémique, dans la grande étude DEVOTE, contrôlée en double aveugle, chez des patients DT2 à risque cardiovasculaire et, en vie réelle, dans l’étude observationnelle européenne EU-TREAT chez des patients DT1 et DT2. L’insuline dégludec (Tresiba®) est indiquée et remboursée dans le traitement des patients DT1, en association avec une insuline prandiale, et DT2, seule ou en combinaison avec des antidiabétiques oraux, un agoniste des récepteurs du glucagon-like-peptide 1 ou une insuline à action rapide.

Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Observational Studies as Topic; Reproducibility of Results

To investigate whether the benefits of switching to insulin degludec observed in the European retrospective chart review study EU-TREAT were dependent on the previous basal insulin used.. People with Type 1 or Type 2 diabetes were switched to insulin degludec from other basal insulins ≥6 months before data collection. Participants were stratified into three groups based on their previous basal insulin: insulin glargine 100 units/ml (Type 1: n=888; Type 2: n=259); insulin detemir (Type 1: n=726; Type 2: n=415); and neutral protamine Hagedorn (Type 1: n=53; Type 2: n=95). Their glycaemic control and hypoglycaemia incidence at 6 and 12 months post-switch vs pre-switch was then evaluated.. Switching to insulin degludec from other basal insulins can improve glycaemic control and/or reduce hypoglycaemia risk in people with diabetes (although there was a nonsignificant reduction in HbA

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Europe; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

To report glycemic control and pregnancy outcome in pregnant women with type 1 diabetes on insulin degludec.. Twenty-two women with type 1 diabetes on degludec from conception to delivery between 2014 and 2018 were compared with 51 pregnant women with type 1 diabetes on glargine.. Baseline characteristics were comparable, however HbA1c was higher at median 9 (range 5-19) weeks in women on degludec compared to women on glargine (6.9% (5.7-8.7); (52 (39-72) mmol/mol) versus 6.4% (5.1-10.1); (46 (32-87) mmol/mol), p = 0.04). HbA1c was similar in late pregnancy (6.3% (5.6-7.1); (45 (38-54) mmol/mol) versus 6.1% (5.2-9.0); (43 (33-75) mmol/mol), p = 0.28). The prevalence of severe hypoglycemia was 3 (14%) versus 6 (12%), p = 1.00 during pregnancy and 0 versus 1, p = 1.00 during hospital admittance after delivery. Most women on degludec used one daily injection in early (20 (91%) versus 25 (49%), p = 0.001) and late pregnancy (21 (96%) versus 19 (37%), p < 0.001). No significant differences in obstetrical and neonatal outcomes were found between the groups. Maternal hospital admittance after delivery was 2 (1-5) versus 3 (2-11) days (p = 0.004).. Glycemic control in late pregnancy, severe hypoglycemia during and immediately after pregnancy as well as pregnancy outcome were comparable in women on degludec or glargine. Degludec initiated preconceptionally may be continued in pregnancy.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Prevalence; Treatment Outcome; Young Adult

Insulin glargine 300 U/ml (U300) was registered based on the EDITION clinical trial program. The aim of this database analysis was to describe the profile of adult U300 recipients with type-1 (T1DM) or type-2 diabetes (T2DM).. The analysis was based on data from the German DIVE/DPV registries. Patients were sampled in May (DIVE) and in March 2018 (DPV) and divided into those who commenced U300 within the 1st year (early adopters) or 2nd year (late adopters). Patients were further compared to patients receiving U100 during the same time period.. Among 581,519 adult patients contained in the databases, 7268 with either T1 or T2DM received U300 and 22,050 U100. Baseline characteristics of U300 and U100 recipients did not differ substantially in both types of diabetes. Patients with T2DM had many risk factors and comorbidities. The median HbA1c (both T1DM and T2DM, 8.1% for U300 and 7.9 and 8.3% for U100) and fasting blood glucose values were similar at baseline. Severe hypoglycemia was less prevalent in T2DM and among recipients of U300 (3.1 vs. 3.9%), whereas in T1DM the rate was higher (10.6 vs. 10.1%). There were minor, but clinically probably irrelevant, differences in age and BMI for T1DM and T2DM between the first and second years. Patients with T2DM being initiated in the second year had a higher HbA1c value (8.6 vs. 8.3%) than those initiated during the first year. Patients in clinical practice showed substantially higher HbA1c values in both T1DM and T2DM, and doses used were lower than those reported from the EDITION trial program. U300 patients had a longer diabetes duration (T1 and T2DM), a higher BMI and received higher basal insulin doses (T1 and T2DM) compared to U100. While HbA1c was comparable, the rate of severe hypoglycemia under U300 was reduced in T2DM but not T1DM with or without adjustment for differences in baseline characteristics in T2DM.. The data confirm the clinical profile documented for U300 in the EDITION studies during the first years of its registration. In an unselected patient population, there was a lesser rate of severe hypoglycemia but at a comparable HbA1c.. German Centre for Diabetes Research (DZD) (01GI1106), the European Foundation for the Study of Diabetes (EFSD) and the German Diabetes Society (DDG). The DIVE registry (organized as Diabetes Agenda 2010 GmbH, Berlin, Germany) received funding from Sanofi, AstraZeneca, Bayer, and Abbott and was conducted under the auspices of diabetesDE.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Registries; Risk Factors

Topics: Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

To compare glycaemic control, hypoglycaemia and treatment discontinuation of insulin glargine 300 units/mL (Gla-300) and insulin degludec (IDeg) in a real-world study of insulin-naïve adults with type 2 diabetes (T2D).. DELIVER Naive D was a retrospective observational study that used electronic medical record data from the IBM Watson Health Explorys database. Insulin-naïve adults with T2D who started Gla-300 or IDeg between March 2015 and September 2017 were identified. Patients were active in the system for ≥12 months before and ≥6 months after starting Gla-300 or IDeg and had HbA1c measurements during 6-month baseline and 3- to 6-month follow-up. Outcomes were compared among 1:1 propensity score-matched cohorts.. In the matched cohorts (n = 638 each), the mean age was 59 years, approximately 53% were male, and mean HbA1c was 9.67% (82 mmol/mol). Mean (SD) HbA1c decreases were comparable in the Gla-300 and IDeg cohorts (-1.67% [2.22] and -1.58% [2.20]; P = 0.51), as were HbA1c target attainment [<7% (53 mmol/mol): 23.8% and 27.4%; P = 0.20; <8% (64 mmol/mol): 55.0% and 57.1%; P = 0.63] and treatment discontinuation (29.2% and 32.6%; P = 0.14). Overall and inpatient/emergency department-associated hypoglycaemia incidences and event rates were similar in both cohorts using fixed 6-month or variable on-treatment follow-up.. Among real-world insulin-naïve adults with T2D, initiation of Gla-300 or IDeg resulted in comparable improvements in glycaemic control and similar rates of hypoglycaemia. These real-world data complement and confirm a randomized trial and other real-world studies.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Propensity Score; Retrospective Studies; Treatment Outcome

This study evaluated real-world clinical outcomes of patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) initiating or transferring to insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100).. This is a retrospective cohort study using data from the Canadian LMC Diabetes Patient Registry. The 4 following cohorts were analyzed: 1) insulin-naïve patients with T2D who initiated Gla-300 or Gla-100, 2) patients with T2D who switched from neutral protamine Hagedorn (NPH) or detemir to Gla-300 or Gla-100, 3) patients with T2D who switched from Gla-100 to Gla-300 and 4) patients with T1D who switched from Gla-100, NPH or detemir to Gla-300.. Of 376 propensity score-matched insulin-naïve patients, 6-month reduction in glycated hemoglobin (A1C) was similar between Gla-300 (-1.78%±1.85%; p<0.001) and Gla-100 (-1.74%±1.87%; p<0.001). In 114 propensity score-matched patients who switched from NPH or detemir, 6-month reduction in A1C was similar between Gla-300 (-0.78%±1.14%) and Gla-100 (-0.70%±1.57%). The 396 patients who switched from Gla-100 to Gla-300 had a significant reduction in A1C (-0.45%±1.39%; p<0.001). In 196 patients with T1D who switched from Gla-100, NPH or detemir to Gla-300, there was a significant reduction in A1C of -0.17%±1.19% (p=0.04).. In a real-world clinical setting, insulin-naïve patients who initiated Gla-300 or Gla-100 showed similar changes in A1C and weight. Patients with T1D or T2D using Gla-300 transferred from another basal insulin had significant reductions in A1C with no change in weight or insulin dose.

Topics: Adult; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Prognosis; Registries; Retrospective Studies

To compare the second-generation basal insulin glargine 300 units/mL (Gla-300) and first-generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D).. DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow-up who switched from basal insulin to Gla-300 were propensity score-matched to 1176 older adults who switched to a first-generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla-100)]. Outcomes were follow-up HbA1c, achievement of HbA1c <7% and <8%, hypoglycaemia incidence and event rates, and healthcare resource utilization.. Following basal insulin switching, HbA1c reductions were greater/similar with Gla-300 versus IDet/Gla-100 (variable follow-up: -0.45% ± 1.40% vs. -0.29% ± 1.57%; P = .021; fixed follow-up: -0.48% ± 1.49% vs. -0.38% ± 1.59%; P = .114), while HbA1c goal attainment was similar in both cohorts. Gla-300 was associated with less hypoglycaemia [event rate: adjusted rate ratio (aRR): 0.63, 95% CI: 0.53-0.75; P < .001] and inpatient/emergency department-associated hypoglycaemia (adjusted hazard ratio: 0.58, 95% CI: 0.37-0.90; P = .016; aRR: 0.43, 95% CI: 0.31-0.60; P < .001) by variable follow-up. By fixed follow-up, hypoglycaemia results significantly or numerically favoured Gla-300.. Among older adults with T2D, switching to Gla-300 versus Gla-100/IDet was associated with greater/similar improvements in glycaemic control, and generally less hypoglycaemia.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemia; Insulin Glargine; Male; Retrospective Studies

A 49-year-old man presented with recurrent altered conscious state suggestive of encephalitis. This was followed by an episode of severe hypoglycemia requiring protracted intravenous glucose administration. Comparing the pharmacokinetic time curves of serum insulin levels on two insulin immunoassays with different insulin analog cross-reactivity allowed the likely diagnosis of surreptitious glargine overdose to be made rapidly.. The differing insulin analog cross-reactivity of serum insulin immunoassays, in this case the Abbott ARCHITECT and Roche Elecsys, allows the presence of insulin analog to be detected. Through comparison of time curves the characteristic signature of the specific causative insulin analog can be identified. This information confirms surreptitious insulin overdose in a timely manner, therefore avoiding the expensive and time-consuming investigations required to exclude alternate causes of severe hypoglycemia.

Topics: Drug Overdose; Humans; Hypoglycemia; Insulin; Insulin Glargine; Pharmacokinetics

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.

Topics: Cohort Studies; Cost Savings; Costs and Cost Analysis; Delivery of Health Care, Integrated; Diabetes Mellitus, Type 2; Drug Compounding; Drug Monitoring; Electronic Health Records; Female; Follow-Up Studies; Glycated Hemoglobin; Health Care Costs; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Glargine; Male; Middle Aged; Patient Acceptance of Health Care; Retrospective Studies; United States

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla-100) or insulin detemir (DET) with ≥1 A1C measurement during 12-month baseline and 18-month follow-up periods were included. Patients with a refill gap of >90 days were considered non-persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow-up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non-persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Topics: Age Factors; Cohort Studies; Diabetes Mellitus, Type 2; Drug Monitoring; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insurance, Health; Male; Medicare; Medication Adherence; Middle Aged; Retrospective Studies; Sex Characteristics; United States

Usage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 to assess whether the benefits observed in clinical trials translate into real-world settings.. This was a retrospective observational study using medical record data obtained by physician survey for patients starting treatment with insulin glargine at a strength of 100 units per milliliter (Gla-100) or Gla-300, or switching to treatment with Gla-300 from treatment with another basal insulin (BI). Differences in dosing and clinical outcomes before versus after treatment initiation or switching were examined by generalized linear mixed-effects models.. Among insulin-naive patients starting BI treatment, no difference in the final titrated dose was observed in patients starting Gla-300 treatment versus those starting Gla-100 treatment [least-squares (LS) mean 0.43 units per kilogram vs 0.44 units per kilogram; P = 0.77]. Both groups had significant hemoglobin A. Insulin-naive patients starting Gla-300 treatment had fewer hypoglycemic events, a similar hemoglobin A. Sanofi US Inc. (Bridgewater, NJ, USA).

Topics: Adult; Aged; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Retrospective Studies

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Peptides

To explore comparative glycaemic control and hypoglycaemia incidence with insulin degludec 100U/mL (IDeg) or insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in trial-level meta-analyses of phase 3a clinical trials including people with type-2 diabetes.. Meta-analyses of HbA. These trial-level meta-analyses suggest that despite greater reductions in FPG, IDeg was associated with less improvement in HbA

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome

Objective Insulin glargine [300 U/mL (Gla-300)] achieved better glycemic control and reduced the risk of hypoglycemia in comparison to glargine [100 U/mL; (Gla-100)] in phase 3 trials. This is the first study to retrospectively evaluate the efficacy and safety of Gla-300 in Japanese type 1 and 2 diabetes patients in a routine clinical setting. Methods We analyzed 20 type 1 diabetes patients and 62 type 2 diabetes patients who switched from Gla-100 to the same dose of Gla-300. Sixty type 2 diabetes patients who continued the use of Gla-100 during the study were included as controls. Results At three months after switching, the HbA1c levels were decreased in the patients with type 1 diabetes, but not to a significant extent. In the type 2 diabetes patients, the HbA1c levels were significantly decreased after switching (p<0.01). In contrast, there was no change in the HbA1c levels of the type 2 diabetes patients who continued the use of Gla-100 over the same period. The BMI values of the type 1 diabetes patients tended to decrease (p=0.06) and there was a significant decrease in the BMI values of the type 2 diabetes patients (p<0.05). There was no change in the BMI values of the type 2 diabetes patients who continued the use of Gla-100. The rates of hypoglycemia and adverse events did not change during the follow-up period. Conclusion In the clinical setting, switching from Gla-100 to the same dose of Gla-300 had a favorable effect on glycemic control and body weight control in Japanese type 1 and type 2 diabetes patients, without any increase in adverse events; however, a prospective study should be performed to confirm these findings.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Middle Aged; Retrospective Studies; Risk Factors

The present post hoc analysis of two 30-week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan-O trial) or basal insulin (LixiLan-L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) ≤7.2 mmol/L, was estimated using the Kaplan-Meier method. In the LixiLan-O and LixiLan-L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan-O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan-L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time-to-target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Kaplan-Meier Estimate; Male; Middle Aged; Peptides; Time Factors; Treatment Outcome

In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ from trial results.. To compare the rates of hypoglycemia-related emergency department (ED) visits or hospital admissions associated with initiation of long-acting insulin analogs vs human NPH insulin in patients with type 2 diabetes.. A retrospective observational study using data from Kaiser Permanente of Northern California from January 1, 2006, through September 30, 2015. Patients with type 2 diabetes who initiated a long-acting insulin analog or NPH insulin were included and censored at death, loss of health plan coverage, change in insulin treatment, or study end on September 30, 2015.. Initiation of basal insulin analogs (glargine or detemir) vs NPH insulin.. The primary outcome was the time to a hypoglycemia-related ED visit or hospital admission and the secondary outcome was the change in hemoglobin A1c level within 1 year of insulin initiation.. There were 25 489 patients with type 2 diabetes who initiated basal insulin therapy (mean age, 60.2 [SD, 11.8] years; 51.9% white; 46.8% female). During a mean follow-up of 1.7 years, there were 39 hypoglycemia-related ED visits or hospital admissions among 1928 patients who initiated insulin analogs (11.9 events [95% CI, 8.1 to 15.6] per 1000 person-years) compared with 354 hypoglycemia-related ED visits or hospital admissions among 23 561 patients who initiated NPH insulin (8.8 events [95% CI, 7.9 to 9.8] per 1000 person-years) (between-group difference, 3.1 events [95% CI, -1.5 to 7.7] per 1000 person-years; P = .07). Among 4428 patients matched by propensity score, the adjusted hazard ratio was 1.16 (95% CI, 0.71 to 1.78) for hypoglycemia-related ED visits or hospital admissions associated with insulin analog use. Within 1 year of insulin initiation, hemoglobin A1c level decreased from 9.4% (95% CI, 9.3% to 9.5%) to 8.2% (95% CI, 8.1% to 8.2%) after initiation of insulin analogs and from 9.4% (95% CI, 9.3% to 9.5%) to 7.9% (95% CI, 7.9% to 8.0%) after initiation of NPH insulin (adjusted difference-in-differences for glycemic control, -0.22% [95% CI, -0.09% to -0.37%]).. Among patients with type 2 diabetes, initiation of a basal insulin analog compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related ED visits or hospital admissions or with improved glycemic control. These findings suggest that the use of basal insulin analogs in usual practice settings may not be associated with clinical advantages for these outcomes.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Emergency Service, Hospital; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Retrospective Studies

To compare clinical outcomes in patients with type 2 diabetes (T2D) switching from insulin glargine 100 units/mL (Gla-100) or insulin detemir (IDet) to insulin glargine 300 units/mL (Gla-300) or insulin degludec (IDeg).. We conducted a retrospective, observational study of electronic medical records for Gla-300/IDeg adult switchers (March 1, 2015 to January 31, 2017) with active records for 12-month baseline (glycated haemoglobin [HbA1c] used a 6-month baseline period) and 6-month follow-up periods. Gla-300 and IDeg switchers were propensity score-matched using baseline demographic and clinical characteristics. Outcomes were HbA1c change and goal attainment (among patients with HbA1c captured at follow-up), and hypoglycaemia with fixed follow-up (intention-to-treat [ITT]; 6 months) and variable follow-up (on-treatment [OT]; to discontinuation or 6 months).. Each matched cohort comprised 1592 patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and <8.0% [64 mmol/mol]) attainment rates were similar for Gla-300 (n = 742) and IDeg (n = 727) switchers. Using fixed follow-up (ITT method), hypoglycaemia incidence decreased significantly from baseline with Gla-300 (all hypoglycaemia: 15.6% to 12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department [ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and event rate were found at follow-up (ITT) for Gla-300 vs IDeg. Using variable follow-up (OT), hypoglycaemia incidence was similar in both groups, but Gla-300 switchers had a lower inpatient/ED hypoglycaemia event rate at follow-up (adjusted rate ratio 0.56; P = .016).. In a real-world setting, switching from Gla-100 or IDet to Gla-300 or IDeg was associated with similar improvements in glycaemic control and hypoglycaemia in adult patients with T2D.

Topics: Aged; Blood Glucose; Comparative Effectiveness Research; Diabetes Mellitus, Type 2; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Propensity Score; Retrospective Studies; Treatment Outcome

Patient characteristics associated with hypoglycaemia frequency during insulin glargine 100 U/mL (Gla-100) titration and clinical outcomes at Week 24 were examined using participant-level data from 16 treat-to-target trials involving individuals with type 2 diabetes mellitus who were inadequately controlled with oral antidiabetes drugs and were initiating Gla-100 (n = 3549). Hypoglycaemia (plasma glucose <3.9 mmol/L or severe) during the first 8 weeks of titration was stratified by number of events (0, 1-3 and ≥4), resulting in 72.5%, 20.6% and 6.9% of participants in each group, respectively. Changes in glycaemia, body weight and insulin dose from baseline to Weeks 12 and 24 were analysed. Hypoglycaemia was more common in participants with lower BMI and fasting C-peptide, and in those undergoing sulfonylurea treatment. Glycaemic outcomes at Week 24 were similar in each hypoglycaemia group, despite the fact that the Week 24 mean daily dose and dose increase for Gla-100 were highest in participants without hypoglycaemia and were lowest in those experiencing ≥4 events. The risk of hypoglycaemia during Gla-100 titration depends mainly on patient characteristics and on sulfonylurea use and may delay dose titration, which apparently has little effect on short-term glycaemic control in a clinical trial setting.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fasting; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Male; Middle Aged; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Time Factors; Treatment Outcome

To conduct two exploratory analyses to compare indirectly the efficacy and safety of simultaneous administration of insulin glargine 100 U (iGlar) and the glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide (Lixi) as a single-pen, titratable, fixed-ratio combination (iGlarLixi [LixiLan trials]) vs sequential administration of iGlar + Lixi (GetGoal Duo trials) in people with type 2 diabetes (T2D).. Propensity-score matching based on baseline covariates was used to compare simultaneous iGlarLixi vs sequential combination of iGlar + Lixi with the addition of Lixi in patients who did not reach the glycated haemoglobin (HbA1c) goal of <53 mmol/mol (<7%) after short-term use of iGlar alone (LixiLan-O vs GetGoal Duo-1 comparison) and vs sequential addition of Lixi in uncontrolled patients after long-term use of iGlar alone (LixiLan-L vs GetGoal Duo-2 comparison).. In both analyses, compared with sequential iGlar + Lixi, iGlarLixi led to significantly greater HbA1c reductions with associated weight loss and significantly more patients reaching target HbA1c <53 mmol/mol despite lower insulin doses. Symptomatic hypoglycaemia rates were similar, despite greater HbA1c reductions with iGlarLixi. Lower rates of gastrointestinal adverse events were observed with iGlarLixi, probably as a result of the more gradual titration of Lixi with iGlarLixi.. Indirect propensity-score-matched exploratory comparisons suggest that early treatment with a simultaneous, titratable, fixed-ratio combination of basal insulin and a GLP-1RA (iGlarLixi) may be more effective and possess better gastrointestinal tolerability than a sequential approach of adding a GLP-1RA in patients with uncontrolled T2D initiating or intensifying basal insulin therapy.

Topics: Adult; Aged; Clinical Trials, Phase III as Topic; Comparative Effectiveness Research; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Peptides; Propensity Score; Randomized Controlled Trials as Topic; Treatment Outcome

The objective of this study was to evaluate glycemic control in type 1 diabetic mellitus patients who were switched from glargine 100 U/ml (Gla-100) to glargine 300 U/ml (Gla-300) in real life practice.. Glycemia based on self-monitoring capillary blood glucose, hypoglycemic events and insulin doses were considered during a two-week period before and after transition from Gla-100 to Gla-300 (period 1). Glycated hemoglobin A1c (HbA. Short term glycemic control was comparable in patients treated with basal insulin Gla-100 or Gla-300 injection. Nocturnal hypoglycemic rate declined quickly after the switch. HbA

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Glargine; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Weight Gain

Topics: Blood Component Removal; Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hyperlipidemias; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Lipoprotein Lipase; Longitudinal Studies; Middle Aged; Pancreatitis, Chronic

To ascertain the effectiveness of implementing the American Diabetes Association/European Association for the Study of Diabetes 2009 consensus algorithm in achieving glycaemic control in patients with type 2 diabetes.. The prospective, observational, open label, product registry was conducted at 38 sites across 7 cities in Pakistan between July 2011 and February 2014. Uncontrolled type 2 diabetes patients were either initiated on or switched to insulin glargine from other basal insulin. Glycated haemoglobin and fasting blood glucose were measured at baseline, 3 and 6 months.. Of the 307 patients, 166(54%) were males. At baseline, the overall mean age was 49.5 ± 8.7 years. Mean duration of diabetes was 7.1 ± 4.5 years. Both fasting blood glucose and glycated haemoglobin levels significantly reduced from baseline to 3 months to 6 months (p<0.01). At 6 months, 18(5.8%) patients reported 41 hypoglycaemic episodes of which 19(46.3%) were asymptomatic and 22(53.6%) were symptomatic. No severe hypoglycaemic episodes were reported.. Insulin initiation and titration as per American Diabetes Association/European Association for the Study of Diabetes guidelines helped in achieving glycaemic targets without increasing the risk of hypoglycaemia.

Topics: Adult; Algorithms; Consensus; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Pakistan; Practice Guidelines as Topic; Prospective Studies

Hypoglycemia is a key barrier to optimum glycemic control in insulin treated diabetes patients. A national level expert group meeting was held at the 11th national insulin summit to analyze published data from clinical studies and guidelines to evolve consensus recommendations on identification and management of hypoglycemia in insulin-treated diabetes patients. This consensus statement emphasizes consideration of suggestive symptoms or blood glucose levels ≤70 mg/dl and ability to self-treat in identification and classification of hypoglycemia. Patient questionnaire administration at each patient visit will enable accurate reporting of hypoglycemia. Patients with strict glycemic control, high glycemic variability, history of severe hypoglycemia, impaired hypoglycemia awareness, long duration of disease or insulin therapy could be at an increased risk of hypoglycemia. Prevention of hypoglycemia should include monitoring and goal setting, patient education, dietary intervention, exercise counseling and medication adjustment. Basal insulin analogues (vs. NPH), rapid-acting insulin analogues (vs. RHI) and premix insulin analogues (vs. BHI) are more appropriate options with superiority of insulin degludec to insulin glargine U100 and IDegAsp to BIAsp 30 to reduce the risk of hypoglycemia. This consensus statement provides practical guidance for physicians in effectively managing and minimizing the risk of hypoglycemia in insulin treated diabetes patients.

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine

Hemoglobin A1C is universally used as a marker for glycemic control and to establish glycemic goals in patients with diabetes. In the older population, experts recommend liberating A1C goals to decrease the risk of hypoglycemia. However, it's not clear which A1C level is optimal for this purpose. This study's aim was to understand the relationship between A1C levels and risk of hypoglycemia.. In a prospective study, we performed continuous glucose monitoring (CGM) on older adults on insulin. Hypoglycemia duration and A1C were measured at baseline while patients were on multiple insulin injections, and again after de-intensification to once-a-day basal insulin with non-insulin agents.. We assessed 65 patients; mean age76±6years with on average 3.7±1.3 insulin injections/day. At baseline, 26% of the patients had A1C<7% (53mmol/mol), 42% between 7.1% and 8% (54-64mmol/mol), 21% between 8.1% and 9% (65-75mmol/mol), and 11% >9% (76mmol/mol). The duration of hypoglycemia (<70mg/dl, <60mg/dl, <50mg/dl) was not different between the A1c groups, regardless of treatment intensity (multiple insulin injections or once-a-day-basal insulin with non-insulin agents).. A1C levels are not associated with hypoglycemia risk in older population with type-2 diabetes on insulin therapy. Higher A1C goals do not protect against hypoglycemia.

Topics: Administration, Oral; Aged; Aged, 80 and over; Aging; Biomarkers; Blood Glucose; Boston; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Monitoring, Ambulatory; Practice Guidelines as Topic; Prospective Studies; Risk; Sulfonylurea Compounds

To re-analyse, using a series of alternative hypoglycaemia definitions, the data from 2 trials, DUAL I and V, in which the once-daily, fixed ratio combination of insulin degludec/liraglutide (IDegLira) was compared with basal insulin therapy.. Post hoc analyses of the DUAL I (patients uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on insulin glargine (IGlar) U100) trials were carried out using different definitions of hypoglycaemia and according to whether treatments were administered in the morning or afternoon. Rates of hypoglycaemia for the definitions of confirmed and American Diabetes Association (ADA)-documented symptomatic hypoglycaemia were compared according to age, gender and body mass index (BMI).. Although hypoglycaemia rates differed according to the alternative hypoglycaemia definitions, rates were consistently lower with IDegLira vs insulin degludec (IDeg) and IGlar U100. Despite glycated haemoglobin concentrations being lower with IDegLira at end of treatment, confirmed and nocturnal-confirmed hypoglycaemia rates were lower for IDegLira vs IDeg and IGlar U100, irrespective of dosing time. The definitions of confirmed and ADA-documented symptomatic hypoglycaemia did not have a significant effect on the treatment difference between IDegLira and IDeg, liraglutide or IGlar U100 when further assessed by baseline age, gender and BMI.. Treatment with IDegLira, vs IDeg and IGlar U100, resulted in lower rates of hypoglycaemia regardless of dosing time and definition of hypoglycaemia used. The choice of hypoglycaemia definition did not influence the results of analyses when stratified by age, sex and BMI.

Topics: Adult; Blood Glucose; Databases, Factual; Diabetes Mellitus, Type 2; Diagnostic Techniques, Endocrine; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies

To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM).. The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed.. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient.. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment.

Topics: Administration, Oral; Cardiovascular Diseases; China; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Direct Service Costs; Drug Administration Schedule; Drug Therapy, Combination; Exenatide; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Incretins; Injections, Subcutaneous; Insulin Glargine; Middle Aged; Models, Economic; Peptides; Quality of Life; Randomized Controlled Trials as Topic; Venoms

We included diabetes type 1 (T1DM) patients with suboptimal glycemic control on morning application glargine (I-Glar) U100, switching them to U300. After six months improvement in HbA1c was observed, while hypoglycemic episodes decreased. Switch from I-Glar U100 to U300 could be a good therapeutic option for that subset of patients.

Topics: Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Pilot Projects

The objective of this study was to assess the cost-effectiveness of insulin degludec versus insulin glargine, from the Spanish NHS in three groups of patients.. A short-term cost utility model was developed to estimate effectiveness results in terms of the total number of hypoglycaemic events and their disutility impact throughout the year on the initial level of quality of life for patients in each treatment.. Degludec was the dominant strategy for T2DM BOT and exhibited an incremental cost-effectiveness ratio of 52.70€/QALY and 11,240.88€/QALY for T1DM B/B and T2DM B/B, respectively. Lower costs are primarily driven by lower nocturnal and severe hypoglycaemic events, which were reduced versus IGlar. Improvements in clinical outcomes in all three patient groups are result of the reduced number of hypoglycaemic events showing 0.0211, 0.0328 and 0.0248 QALYs gained when compared to IGlar for T1DM B/B, T2DM BOT and T2DM B/B, respectively. Different scenario analyses showed that the ICERS were stable to plausible variations in the analysed parameters, except when the same number of SMBG for both treatments is used, with T2DM B/B showing an ICER over the accepted threshold.. This analysis demonstrates that degludec is a cost-effective option in the Spanish NHS, when used in patients currently treated with long-acting insulin.

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Models, Economic; Quality of Life; Quality-Adjusted Life Years; Spain; Time Factors

The Observational Registry of Basal Insulin Treatment (ORBIT) study evaluated the safety of basal insulin (BI) in real-world settings in China.. We analyzed 9002 patients with type 2 diabetes (T2D) inadequately controlled with oral hypoglycemic agents from 8 geographic regions and 2 hospital tiers in China who initiated and maintained BI treatment. Body weight and hypoglycemic episodes were recorded at baseline and 3 and 6 months. Serious adverse events (SAEs) were recorded at 3 and 6 months.. Age, gender, inpatient/outpatient status, body mass index, glycated hemoglobin (HbA1c) at baseline and at the end of study, T2D duration, microvascular complications, BI type, combination with insulin secretagogues, self-monitoring of blood glucose frequency, and insulin dosage, all predicted hypoglycemia. BI use generally did not induce significant weight gain (0.02 kg); weight gain with insulin detemir (-0.30 kg) was less than that with neutral protamine Hagedorn (NPH) insulin (0.20 kg) or insulin glargine (0.05 kg). Overall, general hypoglycemia incidence (5.6% vs. 7.7%) and annual event rate (1.6 vs. 1.8) were similar before and after BI initiation, whereas a slight decrease was noted in severe hypoglycemia incidence (0.6%-0.3%) and frequency (0.05-0.03 events/patient-year). The general hypoglycemia rate was lowest with insulin glargine, whereas there was no significant difference in severe hypoglycemia among the three BI groups. Overall, 3.5% of patients had at least one SAE during the study. Most SAEs were found to be unrelated to BI treatment.. Real-world BI use, particularly insulin detemir and glargine, was associated with only slight weight gain and low hypoglycemia risk in patients with T2D in China.

Topics: Adult; Aged; Blood Glucose; China; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Registries; Risk Factors; Treatment Outcome

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Drug Combinations; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Inventions; Liraglutide; Mobile Applications; Peptides; Self Care; Self-Management; Sweetening Agents; Transdermal Patch

In some circumstances, the premixed insulin should be switched to alternative therapy. The effectiveness and the safety of switching from premixed insulin to insulin glargine plus oral antidiabetic drugs (OADs) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been clarified and, hence, will be assessed in this study. Chinese patients with T2DM (2013 men and women aged 18-75 years) who had received premixed insulin ± OADs for ≥3 months with glycated hemoglobin (HbA1c) ≤ 10% were enrolled in a prospective, observational study conducted at 53 hospitals across China. At baseline and at the discretion of the physician, patients switched from premixed insulin to insulin glargine plus OADs. Changes in HbA1c, fasting plasma glucose (FPG), 2-hour postprandial glucose (PPG), treatment satisfaction, and the incidence of hypoglycemia were assessed for 16 weeks. In total, 1850 patients completed the study. Mean HbA1c level for the group decreased significantly (from 7.8% ± 1.2% at week 1 to 7.0% ± 1.0% at week 16; P < .0001), and 55.2% of patients achieved HbA1c < 7% at week 16. Mean FPG and 2-hour PPG decreased significantly (-1.4 ± 2.2 and -2.1 ± 3.9 mmol/L, respectively; both P < .0001), whereas patient satisfaction improved significantly. Adverse events were reported in 18.7% of patients. Chinese patients with T2DM who switched from premixed insulin to insulin glargine plus OADs achieved significantly improved glycemic control and treatment satisfaction with a low incidence of hypoglycemia. Patients who are most likely to achieve the HbA1c target less than 7% are younger, have shorter disease duration, and have lower baseline HbA1c and FPG levels.

Topics: Administration, Oral; Biomarkers; Blood Glucose; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Prospective Studies; Treatment Outcome

Insulin degludec is an insulin analog with an ultra-long duration of action that exhibits less intra-patient variability in its glucose-lowering activity, and reduces nocturnal, overall, and severe hypoglycemia relative to insulin glargine. The aim of the present study was to evaluate the cost-effectiveness of insulin degludec relative to insulin glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2DBOT), and type 2 diabetes receiving basal-bolus therapy (T2DBB) in Denmark.. A short-term (1 year) cost-utility model was developed to model insulin use, non-severe and severe hypoglycemia, and self-monitoring of blood glucose in patients using insulin degludec and insulin glargine from the perspective of a Danish healthcare payer. Where possible, data were derived from Danish patients with diabetes and meta-analyses of clinical trials comparing insulin degludec with insulin glargine. Using these characteristics, the model estimated costs and quality-adjusted life years (QALYs) gained for the two insulin regimens in each of the three diabetes populations.. Insulin degludec dominated insulin glargine (i.e. reduced costs while improving quality-adjusted life expectancy) in patients with T1D and patients with type 2 diabetes using a basal-only insulin regimen. In the T2DBB cohort, insulin degludec was associated with an incremental cost-effectiveness ratio of DKK 221,063 per QALY gained, which would be considered cost-effective at a willingness-to-pay threshold of EUR 30,000 (∼DKK 224,000) per QALY gained. Sensitivity analysis showed that results were most affected by changes in hypoglycemia rate ratio assumptions, but were broadly insensitive to changes in individual input parameters.. Insulin degludec reduces incidence of hypoglycemia and improves quality-of-life in patients with diabetes. Over a 1-year time horizon, insulin degludec resulted in cost savings relative to insulin glargine in T1D and T2DBOT cohorts, while being cost-effective in T2DBB.

Topics: Cost-Benefit Analysis; Denmark; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

To evaluate the impact of 6 month hypoglycemia on treatment discontinuation and hospitalization of patients initiating basal insulin for type 2 diabetes (T2D) in real-world practice.. This was a retrospective cohort study of patient-level data using electronic medical records (EMRs) in the Predictive Health Intelligence diabetes dataset. Data from adult patients with T2D initiating basal insulin glargine, insulin detemir, or Neutral Protamine Hagedorn insulin between January 2008 and March 2014 was analyzed. The date of first basal insulin prescription in an outpatient setting was the index date. A 12 month baseline prior to the index date was established; follow-up was 6-24 months from the index date. Patients were assigned to cohorts by experience of hypoglycemia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code or blood glucose test) in the first 6 months following the index date; with hypoglycemia and without hypoglycemia cohorts were compared for basal insulin treatment discontinuation and hospitalization.. Overall, 49,062 patients were included; 5159 (10.5%) experienced hypoglycemia in the 6 months following basal insulin initiation. In the first 12 months, 68.1% of patients in the with hypoglycemia cohort discontinued basal insulin versus 53.9% in the without hypoglycemia cohort (p < .0001); more patients in the with hypoglycemia cohort had at least one hospitalization in the first year of follow-up (50.1% vs. 14.6%; p < .0001).. Patients with hypoglycemia soon after initiating basal insulin are at greater risk of discontinuation of their basal insulin therapy and hospitalization versus those who did not have hypoglycemic events within the first 6 months of basal insulin initiation. A limitation of this study is that it was a retrospective analysis of EMR data and the study may not be representative of all US patients with T2D on basal insulin and it cannot be assumed that every hypoglycemic event was recorded.

Topics: Aged; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Risk

To quantify the annual budget impact if all US commercially insured type 1 diabetes mellitus patients on basal-bolus therapy (T1DM. A short-term (1 year) budget impact model was developed to evaluate the costs of IDeg vs. IGlar in three treatment groups (T1DM. Among T1DM. The results of this analysis suggest that the reduced insulin utilization and fewer hypoglycemic episodes associated with IDeg may translate into reduced costs for payers. The model is limited by simplification of a complex disease state and assumptions surrounding disease state, treatment patterns, and costs. Therefore, results may not accurately reflect actual health plans or real-world practice patterns.

Topics: Budgets; Cost Savings; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Needles; United States

Diabetes ketoacidosis (DKA) is a common presentation and complication of type 1 diabetes (T1D). While intravenous insulin is typically used to treat acute metabolic abnormalities, the transition from intravenous to subcutaneous treatment can present a challenge. We hypothesize that co-administration of glargine, a subcutaneous long-acting insulin analog, during insulin infusion may facilitate a flexible and safe transition from intravenous to subcutaneous therapy.. To determine if the practice of administering subcutaneous glargine during intravenous insulin is associated with an increased risk of hypoglycemia, hypokalemia, or other complications in children with DKA.. Retrospective chart review of patients aged 2 to 21 years, presenting to our center with DKA between April 2012 and June 2014. Patients were divided into two groups: those co-administered subcutaneous glargine with intravenous insulin for over 4 hours (G+); and patients with less than 2 hours of overlap (G-).. We reviewed 149 DKA admissions (55 G+, 94 G-) from 129 unique patients. There was a similar incidence of hypoglycemia between groups (25% G+ vs 20% G-, P = 0.46). Hypokalemia (<3.5 mmol/L) occurred more frequently in the G+ group (OR = 3.4, 95% CI 1.7-7.0, P = 0.001). Cerebral edema occurred in 2/55 (3.6%) of the G- group and none of the G+ subjects.. Co-administration of glargine early in the course of DKA treatment is well tolerated and convenient for discharge planning; however, this approach is associated with an increased risk of hypokalemia.

Topics: Adolescent; Child; Child, Preschool; Diabetic Ketoacidosis; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Hypokalemia; Insulin Glargine; Male; Retrospective Studies; Young Adult

Examine real-world outcomes in patients with type 2 diabetes mellitus (T2DM) initiating injectable therapy as part of the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study.. Linked insurance claims and medical record data were collected from 2 large US health insurers (April 1, 2010 to March 31, 2012) of T2DM adults initiating treatment with glargine (GLA) or liraglutide (LIRA). Baseline characteristics were examined and changes in 12-month follow-up outcomes were described for both treatment groups: HbA1c, weight change, hypoglycaemia, persistence, healthcare utilisation and costs.. A total of 4490 patients were included (GLA, 2116; LIRA, 2374). At baseline, GLA patients had significantly higher HbA1c vs LIRA patients (9.72% vs 8.19%; P < .001), lower likelihood of having HbA1c < 7% (7.1% vs 23.8%; P < .001), lower bodyweight (100.9 kg vs 110.9 kg, P < .001), higher Charlson Comorbidity Index score (0.88 vs 0.63; P < .001), and higher diabetes-related costs ($3492 vs $2089; P < .001), respectively. During 12-months of follow-up, treatment persistence was 64%, mean HbA1c reduction was -1.24% and weight change was + 1.17 among GLA patients, and was 49%, -0.51% and -2.74 kg, respectively, among LIRA patients. Diabetes-related costs increased significantly from baseline to follow-up for LIRA patients ($2089 vs $3258, P < .001) but not for GLA patients ($3492 vs $3550, P = .890).. There were clinically relevant baseline differences in both groups, suggesting that GLA and LIRA are prescribed for different patient groups, and highlighting that efficacy results from clinical trials do not always translate into real-world practice. Significant increases in healthcare costs were observed in the LIRA group, warranting further cost-effectiveness analysis.

Topics: Adult; Blood Glucose; Cost-Benefit Analysis; Databases, Factual; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Health Care Costs; Health Services; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Liraglutide; Male; Managed Care Programs; Medication Adherence; Middle Aged; Treatment Outcome; United States

Investigate contributors to treatment satisfaction in type 1 diabetes (T1D).. Post-hoc analysis using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) in 771 T1D patients from two 28-week trials comparing once-daily insulin glargine 100U/mL (Gla-100) with once- or twice-daily NPH neutral protamine Hagedorn (NPH) insulin.. Gla-100 was associated with a significant improvement in treatment satisfaction versus NPH (overall population adjusted mean [standard error] DTSQs change from baseline: +1.13 [0.30] versus -0.04 [0.31]; p=0.006). In the overall population, treatment satisfaction improvement with all insulin regimens was related to less frequent severe hypoglycemia (coefficient-0.077; p=0.040) and HbA1c reduction (-0.066; p=0.082). By treatment regimen, relationships between treatment satisfaction and these outcomes approached or attained statistical significance for NPH insulin, but not Gla-100. In the overall population, predictors of treatment satisfaction improvement included: Gla-100 treatment (estimate 1.17, p=0.006), lower baseline DTSQs (-0.57, p<0.001), study (-1.01, p=0.019), lower severe hypoglycemia rate (0.17, p=0.012), and higher baseline HbA1c (0.44, p=0.014). By treatment regimen, these predictors remained significant for NPH insulin.. Gla-100 resulted in a significant improvement in treatment satisfaction versus NPH insulin, independent of baseline disease characteristics and clinical outcomes.

Topics: Adult; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index

The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.. All persons aged 18-65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006-2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.. A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040).. Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults. KEY MESSAGES The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear. Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin. Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Topics: Adult; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; Young Adult

Among patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery.. Observational study.. Pre- and postoperative holding areas.. One hundred fifty patients with type 2 diabetes using a once daily, evening insulin glargine regimen undergoing ambulatory surgery were included.. None.. To conduct the analysis, patients were divided into four groups based on the percentage of normal evening glargine dose taken. Group 1 took no glargine. Group 2 took 33%-57%. Group 3 took 60%-87% and Group 4 took 100% of their normal dose. The primary outcome was the proportion of patients in each group with blood glucose in the target range (100-180 mg/dL), and the incidence of hypoglycemia (defined as BG <70 mg/dL or symptomatic, requiring glucose).. Group 3 had the highest proportion (78%) of patients within target range (P<.001) and Group 4 had the highest proportion of patients with hypoglycemia (P=.01). Patients in Group 3 were significantly more likely to achieve target blood glucose than patients in either Group 1 (P=.001) or Group 4 (P=.002).. Our study shows that the percent of normal insulin dose given the evening before surgery directly impacts perioperative glucose levels in ambulatory surgery patients. Patients taking 60%-87% of their usual dose the evening before surgery were likely to arrive in target blood glucose range with decreased risk for hypoglycemia. The mean and mode dose taken in Group 3 were 73% and 75%, respectively, suggesting that the optimal dose may be 75% of normal dose.

Topics: Adult; Ambulatory Surgical Procedures; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Postoperative Complications; Preoperative Care

To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study.. In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c ≥ 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months.. A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% ± 2.1%) and detemir groups (2.2% ± 2.1%) was higher than that in the NPH group (2.0% ± 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 ± 2.9 kg) compared with the glargine (+0.1 ± 3.0 kg) and NPH (+0.3 ± 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis.. In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

Topics: China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Intention to Treat Analysis; Lost to Follow-Up; Prospective Studies; Registries; Severity of Illness Index; Weight Gain

In non-critical hospitalized patients with diabetes mellitus, guidelines suggest subcutaneous insulin therapy with basal-bolus regimen, even in old and vulnerable inpatients.. To evaluate safety, efficacy, and benefit on clinical management of the GesTIO protocol, a set of subcutaneous insulin administration rules, in old and vulnerable non-ICU inpatients.. Retrospective, observational study. Patients admitted to Geriatric Clinic of Padua were studied. 88 patients matched the inclusion criteria: type 2 diabetes or hospital-related hyperglycemia, ≥65 years, regular measurements of capillary glycemia, and basal-bolus subcutaneous insulin regimen managed by "GesTIO protocol" for five consecutive days.. ratio of patients with blood glucose (BG) <3.9 mmol/l; number of BG per patient in target range (5-11.1 mmol/l); daily mean BG; and calls to physicians for adjusting insulin therapy.. Mean age was 82 ± 7 years. 9.1% patients experienced mild hypoglycaemia, and no severe hypoglycaemia was reported. The median number of BG per patients in target range increased from 2.0 ± 2 to 3.0 ± 2 (p < 0.001). The daily mean BG decreased from 11.06 ± 3.03 to 9.64 ± 2.58 mmol/l (-12.8%, p < 0.005). The mean number of calls to physicians per patient decreased from 0.83 to 0.45 (p < 0.05).. Treatment with GesTIO protocol allows a safe and effective treatment even in very old and vulnerable inpatients with a faster management insulin therapy.

Topics: Aged; Aged, 80 and over; Blood Glucose; Clinical Protocols; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Geriatrics; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Retrospective Studies

Self-monitoring of blood glucose (SMBG) is used as a means to detect and prevent hypoglycemia in patients with diabetes. However, information on the longitudinal measures (trajectory) of SMBG-based pre- and postprandial glucose fluctuations over time in relation to hypoglycemia is limited. Among patients treated with exenatide once weekly (EQW) or insulin glargine (IG), this study compared SMBG profiles over 52 weeks between patients who did and did not experience hypoglycemia.. Pooled patient-level 52-week longitudinal data of treatment with EQW (n = 531) or IG (n = 219) from three controlled trials were analyzed.. The proportion of patients with at least one episode of hypoglycemia in the EQW and IG groups was 23% and 54%, respectively. The preprandial glucose measures from SMBG were significantly lower among patients who experienced hypoglycemia in both treatment groups compared with those who did not. In patients who experienced hypoglycemia, the average preprandial glucose levels over 52 weeks were lower by 0.64 and 0.66 mmol/L in the EQW and IG groups, respectively (P < 0.01 in both cases) compared with those without hypoglycemia. The average postprandial levels were not significantly different between patients who did and did not experience hypoglycemia in both treatment groups. Among patients with hypoglycemia, the average prebreakfast glucose trajectory was higher by 0.48 mmol/L in the EQW compared with the IG group.. This study has revealed differential trajectories of pre- and postprandial glucose profiles between patients with and without hypoglycemia. However, the SMBG trajectories were similar between patients treated with EQW and IG.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Peptides; Postprandial Period; Risk Factors; Time Factors; Venoms

To assess resource utilization associated with severe hypoglycaemia across three insulin regimens in a large phase 3a clinical programme involving people with Type 1 diabetes treated with basal-bolus insulin, people with Type 2 diabetes treated with multiple daily injections and people with Type 2 diabetes treated with basal-oral therapy.. Data relating to severe hypoglycaemia events (defined as episodes requiring external assistance) from the insulin degludec and insulin degludec/insulin aspart programme (15 trials) were analysed using descriptive statistics. Comparators included insulin glargine, biphasic insulin aspart, insulin detemir and sitagliptin. Mealtime insulin aspart was used in some regimens. This analysis used the serious adverse events records, which documented the use of ambulance/emergency teams, a hospital/emergency room visit ≤ 24 h, or a hospital visit > 24 h.. In total, 536 severe hypoglycaemia events were analysed, of which 157 (29.3%) involved an ambulance/emergency team, 64 (11.9%) led to hospital/emergency room attendance of ≤ 24 h and 36 (6.7%) required hospital admission (> 24 h). Although there were fewer events in people with Type 2 diabetes compared with Type 1 diabetes, once a severe episode occurred, the tendency to utilize healthcare resources was higher in Type 2 diabetes vs. Type 1 diabetes. A higher proportion (47.6%) in the basal-oral therapy group required hospital treatment for > 24 h versus the Type 1 diabetes (5.0%) and Type 2 diabetes multiple daily injections (5.3%) groups.. This analysis suggests that severe hypoglycaemia events often result in emergency/ambulance calls and hospital treatment, incurring a substantial health economic burden, and were associated with all insulin regimens.

Topics: Administration, Oral; Adult; Clinical Trials, Phase III as Topic; Cohort Studies; Costs and Cost Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Severity of Illness Index; Sitagliptin Phosphate

To identify patient-related characteristics and other impact factors predicting early discontinuation of basal insulin therapy in type 2 diabetes in primary care.. A total of 4837 patients who started basal insulin therapy (glargine: n=3175; NPH: n=1662) in 1072 general and internal medicine practices throughout Germany were retrospectively analyzed (Disease Analyser Database: 01/2008-03/2014). Early discontinuation was defined as switching back to oral antidiabetic drugs (OAD) therapy within 90 days after first basal insulin prescription (index date, ID). Patient records were assessed 365 days prior and post ID. Logistic regression models were used to adjust for age, sex, diabetes duration, diabetologist care, disease management program participation, HbA1c, and comorbidity.. Within 3 months after ID, 202 (6.8%) of glargine patients switched back to OAD (NPH: 130 (8.5%); p<0.05). In multivariable logistic regression, predictors of early basal insulin discontinuation were ≥1 documented hypoglycemia before ID (adjusted Odds ratio; 95% CI: 2.20; 1.27-3.82), diagnosed depression (1.31; 1.01-1.70) and referrals to specialists within 90 days after ID (2.06; 1.61-2.63). Diabetologist care (0.57; 0.36-0.89) and glargine treatment (vs. NPH: 0.78; 0.61-0.98) were related to a lower odds of having early insulin discontinuation.. Less than 10% of type 2 diabetes patients switched back to oral antidiabetic drugs within 90 days after start of basal insulin therapy. In particular, patients with baseline depression and frequent or severe hypoglycemia have a higher likelihood for early discontinuation of basal insulin, whereas use of insulin glargine and diabetologist care are related to an increased chance of continuous insulin treatment.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Chi-Square Distribution; Depression; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Substitution; Female; Germany; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Primary Health Care; Referral and Consultation; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Many patients with type 2 diabetes mellitus (T2DM) do not achieve glycaemic control targets on basal insulin regimens. This analysis investigated characteristics, clinical outcomes and impact of concomitant oral antidiabetes drugs (OADs) in patients with T2DM treated with high-dose insulin glargine.. Patient-level data were pooled from 15 randomised, treat-to-target trials in patients with T2DM treated with insulin glargine ± OADs for ≥ 24 weeks. Data were stratified according to whether patients exceeded three insulin dose cut-off levels (> 0.5, > 0.7 and > 1.0 IU/kg). End-points included glycated haemoglobin A1c (A1C), fasting plasma glucose, body weight, and overall, nocturnal and severe hypoglycaemia.. Data from 2837 insulin-naïve patients were analysed. Patients with insulin titrated beyond the three doses investigated had significantly higher baseline A1C levels and were younger, with shorter diabetes duration than those at/below cut-offs (p < 0.05 for all cut-offs); they also had greater weight gain (p < 0.001 for the > 0.5 and > 0.7 IU/kg cut-offs) than those who did not exceed the cut-offs, regardless of concomitant OAD. Patients on concomitant metformin alone had higher insulin doses at Week 24, but achieved greater reductions in A1C, less weight gain and lower hypoglycaemia rates than patients on a concomitant sulfonylurea or metformin plus a sulfonylurea, regardless of whether cut-offs were exceeded.. In patients with T2DM, increasing basal insulin doses above 0.5 IU/kg may not improve glycaemic control; treatment strategies targeting postprandial glucose control should be considered for such patients.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Weight Gain

Insulin assays are designed to detect endogenous insulin, however, insulin assays produced by different manufacturers may detect exogenous recombinant insulin, with varying degrees of cross-reactivity between different assays. We report a fascinating and difficult case of recurrent hypoglycaemia, where the final diagnosis was established with the help of insulin assays using different platforms.. A 24-year-old female presented with recurrent hypoglycaemic episodes on a background of Type 1 diabetes mellitus and a completely resected synovial sarcoma of the right hip several years previously. She reported significant physical, sexual and emotional abuse leading to reduced appetite and weight loss. Despite withdrawing insulin therapy, she experienced profound hypoglycaemic episodes with detectable C-peptide and inappropriately elevated insulin levels, suggesting endogenous hyperinsulinaemic hypoglycaemia; however, localization studies were negative and finally she was found to have exogenous hyperinsulinaemia after discordant insulin levels were detected using two different insulin assays. The C-peptide level was elevated as a result of stimulation by parenteral dextrose and was suppressed after dextrose was ceased. Her Type 1 diabetes mellitus was fabricated and she had factitious hypoglycaemia.. Factitious hypoglycemia is difficult to diagnose and treat. A low blood glucose level, suppressed C-peptide level and an inappropriately elevated insulin level is the classic finding. We were able to make a diagnosis in the present case after discordant insulin levels were detected on the two different insulin assays, signifying cross-reactivities of the recombinant insulin with the assays. A multidisciplinary team approach with psychiatric input is needed to treat such cases.

Topics: Diabetes Mellitus, Type 1; Diagnosis, Differential; Factitious Disorders; Female; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Recurrence; Young Adult

An active 28-year-old man with type 1 diabetes mellitus reported a reduced number of hypoglycaemic episodes following change in basal regime insulin glargine from U100 Lantus to U300 Toujeo. Consequently, an improved quality of life was also reported. Flash-based glucose monitoring was utilised to record 24-hour continuous glucose levels throughout two comparable 60-day periods before and after the change in regimen. Low blood glucose was most likely between 03:00 and 08:00. Nocturnal hypoglycaemic episodes (≤3.9 mmol/L) reduced by an average of 2.5 episodes per week. Severe hypoglycaemic episodes (≤2.9 mmol/L) reduced to an average of 0.4 per week, down from 1.5 per week. Nocturnal hypoglycaemic episodes reduced in frequency and severity. Furthermore, nocturnal hypoglycaemia episodes occurred in a more predictable time window. This was especially important in the reported reduction of impact on the patient's quality of life, as the episodes tended to be associated with anxiety and low mood. Patient education needed to facilitate this change was minimal, and benefits to the patient were great, including decreased sleep disturbances and reduced risk of associated anxiety symptoms.

Topics: Adult; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Quality of Life; Treatment Outcome

Topics: Adolescent; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Suicide, Attempted

The effects of insulin on cardiomyocytes, such as positive inotropic action and glucose uptake are well described. However, in vitro studies comparing long-acting insulin analogues with regard to cardiomyocyte signalling and function have not been systematically conducted.. Insulin receptor (IR) binding was assessed using membrane embedded and solubilised IR preparations. Insulin signalling was analysed in adult rat ventricular myocytes (ARVM) and HL-1 cardiac cells. Inotropic effects were examined in ARVM and the contribution of Akt to this effect was assessed by specific inhibition with triciribine. Furthermore, beating-rate in Cor.4U(®) human cardiomyocytes, glucose uptake in HL-1 cells, and prevention from H2O2 induced caspase 3/7 activation in cardiac cells overexpressing the human insulin receptor (H9c2-E2) were analysed. One-way ANOVA was performed to determine significance between conditions.. Insulin degludec showed significant lower IR affinity in membrane embedded IR preparations. In HL-1 cardiomyocytes, stimulation with insulin degludec resulted in a lower Akt(Ser(473)) and Akt(Thr(308)) phosphorylation compared to insulin, insulin glargine and its active metabolite M1 after 5- and 10-min incubation. After 60-min treatment, phosphorylation of Akt was comparable for all insulin analogues. Stimulation of glucose uptake in HL-1 cells was increased by 40-60 %, with a similar result for all analogues. Incubation of electrically paced ARVM resulted for all insulins in a significantly increased sarcomere shortening, contractility- and relaxation-velocity. This positive inotropic effect of all insulins was Akt dependent. Additionally, in Cor.4U(®) cardiomyocytes a 10-20 % increased beating-rate was detected for all insulins, with slower onset of action in cells treated with insulin degludec. H9c2-E2 cells challenged with H2O2 showed a fivefold increase in caspase 3/7 activation, which could be abrogated by all insulins used.. In conclusion, we compared for the first time the signalling and functional impact of the long-acting insulin analogues insulin glargine and insulin degludec in cardiomyocyte cell models. We demonstrated similar efficacy under steady-state conditions relative to regular insulin in functional endpoint experiments. However, it remains to be shown how these results translate to the in vivo situation.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Mice; Myocytes, Cardiac; Rats; Receptor, Insulin; Signal Transduction

Hypoglycemia remains one of the main challenges of insulin therapy. To reduce insulin-related hypoglycemia at our institution, we restricted inpatient ordering of high glargine doses (≥0.5 U/kg/day) to endocrine staff in May 2013. This retrospective cohort study assesses its effect on hypoglycemia and glycemic control within 48 hours of admission (ADM).. We identified 692 adult patients hospitalized at Boston Medical Center who received glargine upon ADM from November 1, 2012 through April 30, 2013 as the pre-intervention group, and 651 adult patients admitted between November 1, 2013 and April 30, 2014 as the postintervention group. Demographics, medical history, home insulin regimen, concurrent oral diabetes medications or glucocorticoid administration, ADM serum creatinine, all blood glucose levels (BG) ≤48 hours of ADM, and hemoglobin A1c values ≤3 months were assessed. Hypoglycemia was defined as BG ≤70 mg/dL, and hyperglycemia as BG ≥200 mg/dL. Multivariable regression models assessed potential associations between covariates and incidence of hypoglycemia and average BG ≤48 hours of ADM.. Demographics were similar between groups. Significantly less patients received high-dose glargine in the post-intervention group (5.2% vs. 0.3%, P<.001). Incidences of hypoglycemia were significantly lower in the postintervention group (20.9% vs. 17.8%, P<.001 per ADM; 3.4% vs. 2.3%, P = .001 per BG measurements [BGM]). Mean BG levels ≤48 hours of ADM and incidence of hyperglycemia were not significantly different. The adjusted incident rate ratio of hypoglycemia was 0.63 per ADM and 0.74 per BGM in the postintervention group compared to the pre-intervention group (P = .001 and P = .063, respectively).. We found that implementation of a restriction on high doses of glargine resulted in lower rates of hypoglycemia without worsening glycemic control.. ADM = admission BG = blood glucose BGM = blood glucose measurements BMC = Boston Medical Center BMI = body mass index EMR = electronic medical record HgbA1c = hemoglobin A1c IRR = incidence rate ratio NPH = neutral protamine Hagedorn TDD = total daily dose T2D = type 2 diabetes.

Topics: Adult; Aged; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Retrospective Studies

Insulin degludec improved glycemic control in a type 1 diabetes patient undergoing hemodialysis.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Renal Dialysis; Treatment Outcome

Degludec is an ultralong-acting insulin analogue with a flat and reproducible pharmacodynamic profile. As some patients with type 1 diabetes (T1D) fail to achieve 24-h coverage with glargine or detemir despite twice-daily injections, we studied the effect of switching T1D patients from twice-daily glargine or detemir to degludec.. In this prospective observational study, T1D patients on twice-daily glargine or detemir were enrolled. At baseline and 12 weeks after switching to degludec, we recorded HbA1c, insulin dose, 30-day blood glucose self monitoring (SMBG) or 14-day continuous glucose monitoring (CGM), treatment satisfaction (DTSQ), fear of hypoglycemia (FHS). We included 29 patients (mean age 34 ± 11 years; diabetes duration 18 ± 10 years). After switching to degludec, HbA1c decreased from 7.9 ± 0.6% (63 ± 6 mmol/mol) to 7.7 ± 0.6% (61 ± 6 mmol/mol; p = 0.028). SMBG showed significant reductions in the percent and number of blood glucose values <70 mg/dl and in the low blood glucose index (LBGI) during nighttime. CGM showed a significant reduction of time spent in hypoglycemia, an increase in daytime spent in target 70-180 mg/dl, and a reduction in glucose variability. Total insulin dose declined by 17% (p < 0.001), with 24% reduction in basal and 10% reduction in prandial insulin. DTSQ and FHS significantly improved.. Switching from twice-daily glargine or detemir to once daily degludec improved HbA1c, glucose profile, hypoglycemia risk and treatment satisfaction, while insulin doses decreased. ClinicalTrials.govNCT02360254.

Topics: Adult; Biomarkers; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Substitution; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Italy; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Young Adult

To compare effects of basal insulin peglispro (BIL), a hepatopreferential insulin, to insulin glargine (glargine) on aminotransferases and liver fat content (LFC) in patients with type 1 and type 2 diabetes (T1D, T2D).. Data from two Phase 2 and five Phase 3 randomized trials comparing BIL and glargine in 1709 T1D and 3662 T2D patients were integrated for analysis of liver laboratory tests. LFC, measured by magnetic resonance imaging (MRI) at baseline, 26 and 52 weeks, was analyzed in 182 T1D patients, 176 insulin-naïve T2D patients and 163 T2D patients previously treated with basal insulin.. Alanine aminotransferase (ALT) increased in patients treated with BIL, was higher than in glargine-treated patients at 4-78 weeks (difference at 52 weeks in both T1D and T2D: 7 international units/litre (IU/L), P < .001), and decreased after discontinuation of BIL. More BIL patients had ALT ≥3× upper limit of normal (ULN) than glargine. No patient had ALT ≥3× ULN with bilirubin ≥2× ULN that was considered causally related to BIL. In insulin-naїve T2D patients, LFC decreased with glargine but was unchanged with BIL. In T1D and T2D patients previously treated with basal insulin, LFC was unchanged with glargine but increased with BIL. In all three populations, LFC was higher after treatment with BIL vs glargine (difference at 52 weeks: 2.2% to 5.3%, all P < .01).. Compared to glargine, patients treated with BIL had higher ALT and LFC at 52-78 weeks. No severe drug-induced liver injury was apparent with BIL treatment for up to 78 weeks.

Topics: Adipose Tissue; Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Bilirubin; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Liver; Magnetic Resonance Imaging; Male; Metformin; Middle Aged; Pioglitazone; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Thiazolidinediones; Triglycerides

Hypoglycemia has long been recognized as a major barrier to achieving normoglycemia with intensive diabetic therapies. It is a common safety concern for the diabetes patients. Therefore, it is important to apply appropriate statistical methods when analyzing hypoglycemia data. Here, we carried out bootstrap simulations to investigate the performance of the four commonly used statistical models (Poisson, negative binomial, analysis of covariance [ANCOVA], and rank ANCOVA) based on the data from a diabetes clinical trial. Zero-inflated Poisson (ZIP) model and zero-inflated negative binomial (ZINB) model were also evaluated. Simulation results showed that Poisson model inflated type I error, while negative binomial model was overly conservative. However, after adjusting for dispersion, both Poisson and negative binomial models yielded slightly inflated type I errors, which were close to the nominal level and reasonable power. Reasonable control of type I error was associated with ANCOVA model. Rank ANCOVA model was associated with the greatest power and with reasonable control of type I error. Inflated type I error was observed with ZIP and ZINB models.

Topics: Analysis of Variance; Binomial Distribution; Biomarkers; Blood Glucose; Computer Simulation; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Models, Statistical; Poisson Distribution; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk Assessment; Time Factors; Treatment Outcome

Glycemic control in patients with type 2 diabetes is a dynamic process, and changes in risk factors affecting the incidence of hypoglycemia are not well understood. This study explored the association of longitudinal interactive effects of clinical risk factors and concomitant medications on hypoglycemia risk in patients treated with insulin glargine (IG) or exenatide once weekly (EQW).. Pooled patient-level 52-week longitudinal data of treatment with EQW (n = 541) or IG (n = 223) from three controlled trials were analyzed.. Proportions of patients with at least one episode of hypoglycemia in the EQW and IG groups were 23% and 54%, respectively. Compared with patients with HbA1c ≥7% (53 mmol/mol) over time, patients with HbA1c <7% had significantly higher hypoglycemia risk in both groups (95% confidence intervals [CI] of odds ratios [OR]: EQW-1.21, 2.81; IG- 6.26, 9.84). The patterns of interaction effect of changing body mass index (BMI) and HbA1c on hypoglycemia risk differed in the two treatment groups: patients with with BMI >35 kg/m(2) had a 119% increased hypoglycemia risk in the EQW group, but a 57% reduced risk in the IG group. Sulfonylurea-treated patients in the EQW and IG groups had 4.7- and 3-fold additional hypoglycemia risk, respectively, versus non-sulfonylurea-treated patients.. This study revealed differential effects of tight glycemic control and itsinteraction with treatment-induced changes in BMI on hypoglycemia risk its interaction in patients treated with EQW and IG. The residual adverse effect of sulfonylurea was higher in EQW-treated patients.

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Longitudinal Studies; Male; Middle Aged; Peptides; Risk Factors; Venoms

To evaluate real-world clinical outcomes for switching basal insulin analogues [insulin glargine (GLA) and insulin detemir (DET)] among US patients with type 2 diabetes mellitus (T2DM).. Using the GE Centricity Electronic Medical Records database, this retrospective study examined two cohorts: cohort 1, comprising patients previously on GLA and then either switching to DET (DET-S) or continuing with GLA (GLA-C); and cohort 2, comprising patients previously on DET and then either switching to GLA (GLA-S) or continuing with DET (DET-C). Within each cohort, treatment groups were propensity-score-matched on baseline characteristics. At 1-year follow-up, insulin treatment patterns, glycated haemoglobin (HbA1c) levels, hypoglycaemic events, weight and body mass index (BMI) were evaluated.. The analysis included 13 942 patients: cohort 1: n = 10 657 (DET-S, n = 1797 matched to GLA-C, n = 8860) and cohort 2: n = 3285 (GLA-S, n = 858 matched to DET-C, n = 2427). Baseline characteristics were similar between the treatment groups in each cohort. At 1-year follow-up, in cohort 1, patients in the DET-S subgroup were significantly less persistent with treatment, more likely to use a rapid-acting insulin analogue, had higher HbA1c values, lower HbA1c reductions and lower proportions of patients achieving HbA1c <7.0 or <8.0% compared with patients in the GLA-C subgroup, while hypoglycaemia rates and BMI/weight values and change from baseline were similar in the two subgroups. In cohort 2, overall, there were contrasting findings between patients in the GLA-S and those in the DET-C subgroup.. This study showed contrasting results when patients with T2DM switched between basal insulin analogues, although these preliminary results may be subject to limitations in the analysis. Nevertheless, this study calls into question the therapeutic interchangeability of GLA and DET, and this merits further investigation.

Topics: Aged; Body Mass Index; Body Weight; Databases, Factual; Diabetes Mellitus, Type 2; Drug Substitution; Electronic Health Records; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insulin, Short-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States

The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs.. Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models.. A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant.. Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.

Topics: Body Mass Index; Body Weight; Comorbidity; Costs and Cost Analysis; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Propensity Score; United Kingdom

Poor glycemic control and the resulting development of complications of type 2 diabetes (DM2T) increase treatment costs. If adequate glycemic control cannot be achieved by lifestyle modifications and oral antidiabetic (OAD) therapy, initiation of insulin therapy is recommended. Cost effectiveness of basal insulins of the type NPH or glargine in combination with OAD for the treatment of DM2T was examined in a number of pharmacoeconomic studies. However, none of these studies were conducted in the Czech Republic. Therefore, the aim of the project POET2 was to compare annual direct medical costs of treating DM2T after addition of insulin NPH or glargine to OAD therapy in a clinical practice setting in the Czech Republic.. Data collected from 1967 patients who met the criteria for inclusion into the non-interventional prospective registry POET2 (DM2T, ongoing OAD therapy, glycated hemoglobin HbA1c > 6 % IFCC) and who were observed for 12 months following the start of insulin therapy (glargine: n = 1061 vs NPH: n = 906) were analysed. Costs of treatment were analysed from the perspective of health insurance companies and included costs of medication, medical devices and medical procedures.. In both treatment groups a reduction of HbA1c (glargine group: by 1.77 % IFCC vs NPH group: by 1.73 % IFCC) and fasting plasma glucose (glargine group: by 3.67 mmol/l vs NPH group: by 3.63 mmol/l) was observed. Insulin glargine therapy was associated with the incidence of a significantly lower number of documented symptomatic hypoglycemic events (glargine group: 0.840 events per patient and year of treatment vs. NPH group: 1.053 events per patient and year of treatment; p < 0.05). Overall annual direct medical costs associated with the initiation of basal insulin treatment were higher on average by 2547.07 CZK among patients treated with insulin glargine (glargine group: 12173.09 ± 4169.44 CZK vs NPH group: 9626.02 ± 3432.79 CZK; p < 0.001) due to higher costs of medication (glargine group: 7992.97 ± 4001.81 CZK vs NPH group: 3784.2 ± 3181.48 CZK; p < 0.001). By contrast, costs of medical devices (glargine group: 2332.08 ± 917.84 CZK vs NPH group: 3893.95 ± 989.79 CZK; p < 0.001) and medical procedures (glargine group: 1848.04 ± 684.89 CZK vs NPH group: 1947.87 ± 685.43 CZK; p < 0.001) were lower among patients treated with insulin glargine.. Addition of basal insulin to OAD therapy was an efficacious therapeutic intervention for the treatment of DM2T in a clinical practice setting in the Czech Republic. Overall annual direct medical costs were higher among patients treated with insulin glargine than among patients treated with insulin NPH. However, costs of medical devices and medical procedures were lower in the insulin glargine group. In addition, incidence of hypoglycemia was significantly lower among patients treated with insulin glargine.

Topics: Adult; Aged; Czech Republic; Diabetes Mellitus, Type 2; Direct Service Costs; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Prospective Studies; Registries

This study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills-based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus.. Retrospective analysis of data from 892 DAFNE participants from 11 UK centres.. Mean HbA1c 12 months after DAFNE was lower in those using twice- rather than once-daily basal insulin after correcting for differences in baseline HbA1c , age and duration of diabetes; difference -2 (95% CI -3 to -1) mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7 to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c  ≥ 58 mmol/mol, who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice-daily basal insulin users. In the group with greatest fall in HbA1c , the estimated relative risk for severe hypoglycaemia in twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88-3.36, P = 0.110).. After structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c , independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.

Topics: Adult; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Logistic Models; Male; Middle Aged; Patient Education as Topic; Retrospective Studies; Self Care; Treatment Outcome

Topics: Blood Glucose; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Glargine

Few articles have described fluctuations in glutamic acid decarboxylase antibody (GADAb) levels after a diagnosis of slowly progressive type 1 diabetes (SPIDDM). Here, we present a case in which GADAb levels exponentially increased after initiating and stopping insulin. A 64-year-old female patient newly diagnosed with SPIDDM was admitted and started multiple daily insulin injections. The patient's GADAb titer was 6.9 U/mL (normal: <1.4 U/mL) and the patient had a type 1 diabetes susceptible HLA class II haplotype known in the Japanese population as: DRB1*04:05-DQB1*04:01. When the patient's "honeymoon period" set in, hypoglycemia was observed and the dose of insulin was reduced. Two months after the diagnosis, 1 unit of insulin glargine/day was being injected and the patient demonstrated good glycemic control. Subsequently, the patient's home doctor recommended that insulin injections be stopped. Three months after the diagnosis, the patient's GADAb titer suddenly increased to 1600 U/mL. The patient's GADAb titer decreased but was still positive (40 U/mL) 36 months after diagnosis. HbA1c levels were maintained below 7%, and oral glucose tolerance tests at 10, 26, and 36 months after diagnosis suggested that the patient had preserved insulin secretion. To the best of our knowledge, this is the first report that describes exponential increases in GADAb after initiating and stopping insulin in a patient with SPIDDM.

Topics: Autoantibodies; Blood Glucose; Diabetes Mellitus, Type 1; Fasting; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Glutamate Decarboxylase; Glycated Hemoglobin; Haplotypes; Histocompatibility Antigens Class II; Humans; Hypoglycemia; Insulin; Insulin Glargine; Japan; Middle Aged

Due to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3-6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal-bolus therapy (BBT) regimen in T2DM patients in daily clinical practice.. This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT).. A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m(2); pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean -0.94% and -0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean -1.29% and -1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1).. Intensifying glargine-based BOT or glulisine-based SIT to a BBT regimen in poorly controlled T2DM patients in daily routine care led to marked improvements of glycemic control and was well tolerated.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Male; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome; Young Adult

Biphasic insulin aspart 30 allows fewer daily injections versus basal-bolus insulin regimens, which may improve adherence and treatment outcome. This sub-analysis of the observational A1chieve study assessed clinical safety and effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes previously receiving basal-bolus insulin regimens.. A1chieve was an international, open-label, 24-week study in people with type 2 diabetes starting/switching to biphasic insulin aspart 30, insulin detemir or insulin aspart. This sub-analysis assessed patients switching from insulin glargine- or neutral protamine Hagedorn insulin-based basal-bolus insulin regimens to biphasic insulin aspart 30.. 1024 patients were included. At 24 weeks, glycated haemoglobin and fasting plasma glucose were significantly reduced from baseline in both cohorts (all p<0.001). The proportion reporting any hypoglycaemia, major hypoglycaemia or nocturnal hypoglycaemia was significantly reduced after 24 weeks (all p<0.05). No serious adverse drug reactions were reported. Both cohorts had significantly improved health-related quality of life (HRQoL; p<0.001).. 24 weeks after switching from basal-bolus insulin regimens to biphasic insulin aspart 30, glycaemic control and HRQoL were significantly improved, and hypoglycaemia was significantly reduced. This suggests that people with type 2 diabetes inadequately controlled on basal-bolus insulin regimens can consider biphasic insulin aspart 30.

Topics: Adult; Africa, Northern; Aged; Asia; Biomarkers; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Latin America; Male; Middle Aged; Middle East; Quality of Life; Russia; Time Factors; Treatment Outcome

OBJECTIVE To determine a cutoff score for clinically meaningful fear of hypoglycemia (FoH) on the Hypoglycemia Fear Survey Worry subscale (HFS-W). RESEARCH DESIGN AND METHODS Data on the HFS-W, history of hypoglycemia, emotional well-being (World Health Organization-5 well-being index), and distress about diabetes symptoms (Diabetes Symptom Checklist-Revised) were available from Dutch patients with type 2 diabetes who were treated with oral medication or insulin (n = 1,530). Four criteria were applied to define a threshold for clinically meaningful FoH: 1) modal score distribution (MD criterion), 2) scores 2 SDs above the mean (SD criterion), 3) concurrent validity with severe hypoglycemia and suboptimal well-being (CV criterion), and 4) an elevated score (≥3) on more than one HFS-W item (elevated item endorsement [EI criterion]). Associations between the outcomes of these approaches and a history of severe hypoglycemia and suboptimal well-being were studied. RESULTS Of the 1,530 patients, 19% had a HFS-W score of 0 (MD criterion), and 5% reported elevated FoH (HFS-W ≥ mean + 2 SD; SD criterion). Patients with severe hypoglycemia reported higher HFS-W scores than those without (25 ± 20 vs. 15 ± 17; P < 0.001). Patients with suboptimal well-being reported higher HFS-W scores than those with satisfactory well-being (20 ± 18 vs. 13 ± 15; P < 0.001, CV criterion). Elevated FoH (defined by the EI criterion) was seen in 26% of patients. The SD and EI criteria were the strongest associated with history of severe hypoglycemia. The EI criterion was the strongest associated with suboptimal well-being. CONCLUSIONS Although no definite cutoff score has been determined, the EI criterion may be most indicative of clinically relevant FoH in this exploratory study. Further testing of the clinical relevance of this criterion is needed.

Topics: Aged; Diabetes Mellitus, Type 2; Fear; Female; Health Surveys; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prevalence; Psychiatric Status Rating Scales; Regression Analysis; Risk Factors; Sulfonylurea Compounds; Surveys and Questionnaires

We aimed to identify predictors of hypoglycaemia in patients with poorly controlled type 2 diabetes treated with a single daily bolus of insulin glulisine on top of insulin glargine and oral antidiabetic drugs (basal-plus regimen).. We retrospectively analysed four large basal-plus trials including 713 patients (47% female) with type 2 diabetes, mean age of 59.9 ± 9.5 years and diabetes duration of 11 ± 7.0 years. Predictors for symptomatic, severe and nocturnal hypoglycaemia were identified by multivariate logistic regression analyses, calculation of odds ratios (ORs) and Wald 95% confidence intervals (CIs).. Mean numbers of hypoglycaemic events per year were 4.64 ± 11.4 (symptomatic < 60 mg/dl), 0.59 ± 2.28 (nocturnal) and 0.03 ± 0.22 (severe). A total of 44.5% of patients reached the composite endpoint of glycated haemoglobin (HbA1c) <7.0% plus no severe hypoglycaemia, and 26.7% reached the composite of HbA1c <7.0% plus no symptomatic hypoglycaemia. Predictors of nocturnal and symptomatic hypoglycaemia were female gender (OR 1.82; 95% CI 1.07-3.11 and OR 1.89; 95% CI 1.31-2.78), diabetes duration >10 versus <5 years (OR 2.61; 95% CI 1.03-6.59 and OR 2.01; 95% CI 1.15-3.51) and higher basal insulin dose (per unit of increase) (OR 1.01; 95% CI 1.00-1.03 and OR 1.01; 95% CI 1.00-1.02). Conversely, a higher body mass index (BMI) (27-30 vs. <27 kg/m(2) and >30 vs. <27 kg/m(2) ) conferred a reduced risk of symptomatic hypoglycaemia with an OR of 0.53 (95% CI 0.31-0.90) and an OR of 0.61 (95% CI 0.39-0.97).. Female gender, a long diabetes duration and higher basal insulin dose were predictors of hypoglycaemia, while protection was provided by BMI > 30. These results may help to successfully establish basal-plus insulin regimen in individual patients on their transition from basal-only to basal-bolus treatment.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Multicenter Studies as Topic; Predictive Value of Tests; Randomized Controlled Trials as Topic; Retrospective Studies; Sex Factors; Time Factors; Treatment Outcome

The aim was to observe the effects of switching from neutral protamine Hagedorn (NPH) insulin to insulin glargine on glycaemic control in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice in Italy. This multicenter, observational, retrospective study included 1,011 patients with T2DM who switched from NPH insulin to glargine or were maintained on NPH insulin. The primary outcome was change in HbA1c over 4-8 months. Secondary outcomes included fasting blood glucose (FBG), insulin dose, and hypoglycaemia. The intention-to-treat population consisted of 996 patients (glargine 496; NPH 500). Prior to switching, HbA1c was higher in the glargine than the NPH group [mean (±SD) 8.8 ± 1.4 vs. 7.9 ± 1.2%; p < 0.001]. HbA1c decreased after 4-8 months with glargine (8.2 ± 1.4%; p < 0.001) but not with NPH (8.0 ± 1.4%; p = 0.20). Similar results were observed for FBG. The daily dose of glargine increased from 0.22 ± 0.10 U/kg at the switch to 0.26 ± 0.11 U/kg at study end, while the NPH dose remained stable (0.19 ± 0.09-0.20 ± 0.09 U/kg). While not statistically significant, the percentage of patients with hypoglycaemic episodes during the last month of treatment tended to be less with glargine. No significant change in body weight occurred in either group. Switching patients from NPH insulin to insulin glargine in a real-life setting was associated with significant improvement in glycaemic control. The increase in glargine dose was not accompanied by increased hypoglycaemia or weight gain.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Italy; Male; Retrospective Studies

We performed a comparative analysis of the use of long-acting insulin (analogues) neutral protamine hagedorn (NPH), detemir (Det) and glargine (Gla), and quantified injection frequencies and daily insulin doses in patients with type 1 and 2 diabetes in daily practice.. A total number of 51 964 patients from 336 centres in Germany and Austria with type 1 and 2 diabetes with exclusive insulin therapy were retrospectively analysed.. A total number of 42.1%/75.9% (type 1/type 2) of patients used NPH, 19.9%/6.7% Det and 38.0%/17.4% Gla, with similar glycaemic control and proportion of severe hypoglycaemia for NPH/Det/Gla in type 1 (Mean HbA(1c) 7.98%/7.98%/8.07%; mean proportion of severe hypoglycaemia 11.06%/11.93%/10.86%) and type 2 diabetes (Mean HbA(1c) 7.61%/7.78%/7.61%; mean proportion of severe hypoglycaemia 5.66%/4.48%/5.03%). In type 1 diabetes, the mean daily injection frequencies of NPH versus Det versus Gla were 1.9 vs 1.8 vs 1.1, and total daily insulin injections were 5.3 vs 5.6 vs 5.0. The adjusted mean daily basal insulin doses were 0.36, 0.39 and 0.31 IU/kg, mean daily total insulin dose was lowest for Gla (0.74 IU/kg), followed by NPH (0.76 IU/kg) and Det (0.81 IU/kg). In type 2 diabetes patients, mean daily injection frequencies were 1.6 for NPH, 1.4 for Det and 1.1 for Gla, total daily insulin injections were 4.0 vs 4.1 vs 3.6. The mean daily basal insulin dosages were 0.30 IU/kg (NPH), 0.33 IU/kg (Det) and 0.29 IU/kg (Gla), mean total insulin doses per day were 0.63 IU/kg (NPH), 0.77 IU/kg (Det) and 0.67 IU/kg (Gla).. In a 'real-world' setting, the injection frequencies and doses of basal and total insulin per day are lowest with the use of insulin glargine compared with NPH-insulin or insulin detemir at similar glycaemic control and rates of severe hypoglycaemia.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies

Diabetes accounts for almost 15% of all direct healthcare expenditures. Managed care organizations try to reduce costs and improve patient outcomes. Increasing patient persistence with antidiabetes treatment could help achieve these goals.. A retrospective study was conducted using the Optum Research Database (Optum, Eden Prairie, MN) to analyze clinical and economic outcomes associated with initiation of insulin glargine via a disposable pen (GLA-P) or vial and syringe (GLA-V) among adult, insulin-naive patients with type 2 diabetes mellitus (T2DM). Propensity-matched patient cohorts were assessed for persistence with insulin therapy, glycated hemoglobin (A1C), hypoglycemic events (based on diagnosis codes), and healthcare costs (total paid amount of adjudicated claims) after follow-up at 1 year.. In 1,308 matched patients, persistence was significantly higher (P=0.011) and longer (P=0.001) with GLA-P. Follow-up A1C values were significantly lower (P=0.038), and decreases in A1C from baseline significantly larger (P=0.043), in GLA-P than in GLA-V. Significantly fewer hypoglycemic events (P=0.042) were experienced, and a lower rate of diabetes-related inpatient admissions (P=0.008) was reported in GLA-P than GLA-V. Despite higher study drug costs with GLA-P than GLA-V, all-cause and diabetes-related healthcare costs were similar.. In insulin-naive patients with T2DM, initiation of insulin glargine using the disposable pen rather than the vial and syringe is associated with higher persistence, better A1C control, and lower rates of hypoglycemia. The higher study drug costs associated with pen use do not increase total all-cause or diabetes-related healthcare costs. This may help treatment selection for patients with T2DM in a managed care setting.

Topics: Adolescent; Adult; Aged; Blood Glucose; Databases, Factual; Diabetes Mellitus, Type 2; Disposable Equipment; Female; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Managed Care Programs; Medication Adherence; Middle Aged; Retrospective Studies; Self Administration; Syringes; United States

Topics: Antineoplastic Agents; Diabetes Mellitus, Type 1; Fatal Outcome; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Indoles; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Protein Kinase Inhibitors; Pyrroles; Sunitinib

Type-2 diabetes mellitus (T2DM) is a progressive disease, and many patients eventually require insulin therapy. This study examined real-world outcomes of switching basal insulin analogs among patients with T2DM.. Using two large United States administrative claims databases (IMPACT(®) and Humana(®)), this longitudinal retrospective study examined two cohorts of adult patients with T2DM. Previously on insulin glargine, Cohort 1 either continued insulin glargine (GLA-C) or switched to insulin detemir (DET-S), while Cohort 2 was previously on insulin detemir, and either continued insulin detemir (DET-C) or switched to insulin glargine (GLA-S). One-year follow-up treatment persistence and adherence, glycated hemoglobin (HbA1c), hypoglycemia events, healthcare utilization and costs were assessed. Selection bias was minimized by propensity score matching between treatment groups within each cohort.. A total of 5,921 patients (mean age 60 years, female 50.0%, HbA1c 8.6%) were included in the analysis (Cohort 1: IMPACT(®): n = 536 DET-S matched to n = 2,668 GLA-C; Humana(®): n = 256 DET-S matched to n = 1,262 GLA-C; Cohort 2: n = 419 GLA-S matched to n = 780 DET-C), with similar baseline characteristics between treatment groups in each cohort. During 1-year follow-up, in Cohort 1, DET-S patients, when compared with GLA-C patients, had lower treatment persistence/adherence with 33-40% restarting insulin glargine, higher rapid-acting insulin use, worse HbA1c outcomes, significantly higher diabetes drug costs, and similar hypoglycemia rates, health care utilization and total costs. However, in Cohort 2 overall opposite outcomes were observed and only 19.8% GLA-S patients restarted insulin detemir.. This study showed contrasting clinical and economic outcomes when patients with T2DM switched basal insulin analogs, with worse outcomes observed for patients switching from insulin glargine to insulin detemir and improved outcomes when switching from insulin detemir to insulin glargine. Further investigation into the therapeutic interchangeability of insulin glargine and insulin detemir in the real-world setting is needed.

Topics: Adult; Aged; Costs and Cost Analysis; Databases, Factual; Diabetes Mellitus, Type 2; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Longitudinal Studies; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; United States

Optimizing glycemic control in patients with type 2 diabetes mellitus (T2DM) not controlled with ≥ 1 oral antidiabetes drugs (OADs) is challenging. Many therapeutic options exist; however, data comparing the effectiveness of different strategies are lacking for the management of patients with T2DM. Our study aim was to provide comparative data on efficacy and hypoglycemia when initiating insulin glargine (glargine) versus alternative treatment options (not including the newest antidiabetes agents, glucagon-like peptide [GLP]-1 receptor agonists, dipeptidyl peptidase [DPP]-4 inhibitors or sodium-glucose linked transporter [SGLT]-2 inhibitors) in insulin-naive patients with T2DM who remained uncontrolled with OADs.. Patient-level data were pooled from 9 randomized controlled trials of ≥ 24 weeks duration with comparable patient populations. The effect of adding glargine was compared with intensification of lifestyle interventions or OADs, addition of neutral protamine Hagedorn (NPH) insulin, insulin lispro, premixed insulin, or all comparators pooled, on patient glycated hemoglobin (HbA1c) level, fasting plasma glucose level, weight, and hypoglycemia.. A greater proportion of patients achieved a target HbA1c level ≤ 7.0% with glargine treatment than with pooled comparators, intensification of OADs, or lifestyle interventions; there was no difference when compared with NPH, premixed, or insulin lispro use. The rate for reported hypoglycemic events was lower for glargine use than for pooled comparators or other insulins, but higher compared with intensification of lifestyle interventions or OADs. When stratified by baseline HbA1c level, efficacy/target attainment with glargine use was better than for pooled comparators across all HbA1c strata; OAD intensification, when baseline HbA1c level was ≥ 8.0%; and premixed insulin if baseline HbA1c level was < 8.0%; but similar to other insulins for all other categories. The incidence of reported hypoglycemia was less frequent with glargine use than other insulins, but more frequent than intensification of lifestyle interventions or OADs.. When adequate glycemic control is not achieved using OADs in patients with T2DM, initiating insulin glargine is generally less likely to elicit hypoglycemia than initiating NPH, premixed, or prandial insulins, and the benefit-risk balance supports initiating insulin rather than intensification of OAD therapy when baseline HbA1c level is ≥ 8.0%.

Topics: Administration, Oral; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Insulins; Randomized Controlled Trials as Topic; Sulfonylurea Compounds

Cardiovascular risk factors (CVRFs) may complicate optimization of therapy in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetes drugs (OADs). We assessed the influence of patient baseline CVRFs on efficacy and rate of hypoglycemia with use of insulin glargine (glargine) added to ongoing OAD treatment compared with alternative therapeutic options; namely, intensification of lifestyle interventions or adding OADs, neutral protamine Hagedorn (NPH), lispro, or premixed insulin in patients failing OADs.. Patient-level data were pooled from 9 randomized controlled trials of glargine and comparators for 24 weeks in insulin-naive patients with T2DM inadequately controlled on OADs. Efficacy (goal attainment-glycated hemoglobin (HbA1c) level ≤ 7.0% or decrease ≥ 1.0% change from baseline) and hypoglycemia rates (symptomatic, confirmed, nocturnal, or severe) were compared for patients treated with glargine (n = 1462) and pooled (n = 1476) and individual comparators, overall; and in patients with hypertension (~69%), dyslipidemia (~58%), history of cardiovascular disease (~25%), or any CVRF (~83%) at baseline.. The patient groups were well-balanced at baseline (HbA1c level 8.7%; diabetes duration, 8.6 years). Use of glargine was associated with greater patient goal attainment (57.7% vs 51.4% for HbA1c level ≤ 7.0%; P < 0.001), modestly larger reductions in HbA1c level (-1.68% vs -1.51%; P < 0.001), and less symptomatic hypoglycemia than occurred with pooled comparators, regardless of patient CVRFs (5.04 vs 7.01 events/patient-year of exposure, respectively; P < 0.001). Reductions in HbA1c level and hypoglycemia rates were significantly greater with glargine use than with intensification of OADs or lifestyle modifications, overall, and in patients with any CVRF. Reductions in HbA1c level were greater and hypoglycemia rates lower with use of glargine compared with premixed insulin, overall, and in patients with any CVRF. Reductions in HbA1c level were similar and hypoglycemia rates lower with use of glargine, NPH, and lispro insulin, regardless of patient CVRFs.. The glycemic benefits of glargine use compared with alternative therapeutic options are maintained without excess hypoglycemia in patients with CVRFs.

Topics: Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

The purpose of this analysis is to evaluate the safety and effectiveness of insulin initiation with once-daily insulin detemir (IDet) or insulin glargine (IGlar) in real-life clinical practice in Turkish patients with type 2 diabetes mellitus (T2DM).. This was a 24-week multinational observational study of insulin initiation in patients with T2DM.. The Turkish cohort (n = 2886) included 2395 patients treated with IDet and 491 with IGlar. The change in glycosylated haemoglobin (HbA1c) from the pre-insulin levels was -2.21% [95% confidence interval (CI) -2.32, -2.09] in the IDet group and -1.88% [95% CI -2.17, -1.59] in the IGlar group at the final visit. The incidence rate of minor hypoglycaemia increased in both groups from the pre-insulin to the final visit (+0.66 and +2.23 events per patient year in the IDet and IGlar groups, respectively). Weight change in the IDet group was -0.23 kg [95% CI -0.49, 0.02 kg], and +1.55 kg [95% CI 1.11, 2.00 kg] in the IGlar group. Regression analysis with adjustment for previously identified confounders (age, gender, duration of diabetes, body mass index, previous history of hypoglycaemia, microvascular disease, number and change in oral anti-diabetic drug therapy, HbA1c at baseline and insulin dose) identified an independent effect of insulin type (IDet versus IGlar) with a risk of at least one episode of hypoglycaemia (odds ratio (OR): 0.33 [95% CI 0.21, 0.52], p <0.0001), and weight loss ≥1 kg (OR: 1.75 [95% CI 1.18, 2.59], p = 0.005), but not on HbA1c (+0.05% [95% CI -0.15, 0.25%], p = 0.6).. Initiation of basal insulin analogues, IDet and IGlar, were associated with clinically significant glycaemic improvements. A lower risk of minor hypoglycaemia and greater odds of weight loss ≥1 kg was observed with IDet compared with IGlar.. NCT00825643 and NCT00740519.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; International Agencies; Male; Middle Aged; Prognosis; Prospective Studies

An ideal insulin regimen for children and adolescents with type 1 diabetes mellitus (T1DM) should be physiological, flexibile and predictable, protecting against hypoglycaemia. The aim of this study was to evaluate the influence of insulin analogues on glycaemic control and the occurance of hypoglycaemic episodes in children and adolescents with T1DM.. The study group consisted of 151 children and adolescents (90 boys, 61 girls) treated with human insulins for at least 12 months before introducing insulin analogues. All the patients were divided into two groups: the group I consisted of 72 (47.7%) patients treated with three injections of regular human insulin before meals and long-acting analogue (RHI/LA), and the group II of 79 (52.30%) patients treated with a combination of rapid-acting and long-acting analogue (RA/LA). The levels of glycated hemoglobin (HbA1c) and the number of hypoglycaemic episodes were assessed at the beginning of therapy with insulin analogues, and after 6 and 12 months.. The mean HbA1c was significantly lower in the group I (RHI/LA) after 6 months (9.15% vs 8.20%, p < 0.001) and after 12 months (9.15% vs 8.13%, p < 0.001) as well as in the group II (RA/LA) after 6 months (9.40% vs 8.240%, p < 0.001) and after 12 months of insulin analogues treatment (9.40% vs 8.38%, p < 0.001). The frequency of severe hypoglycaemia was significantly lower in both groups after 6 months (in the group I from 61.1% to 4.2% and in the group II from 54.4% to 1.3%, p < 0.001), and after 12 months (in the group I from 61.1% to 1.4% and in the group II from 54.4% to 1.3%, p < 0.001).. Significantly better HbA1c values and lower risk of severe hypoglycaemia were established in children and adolescents with T1DM treated with insulin analogues.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Retrospective Studies

In addition to medications, patient education is thought to have important beneficial effects in the management of patients with type 2 diabetes mellitus.. The aim of the authors was to evaluate the additional effect of patient education on glycemic control and some aspects of lifestyle in a non-interventional study.. Patients between the ages of 18 and 75 were involved. Study sites which provided standardized education program recruited educated patients, while sites which provided diabetes counseling recruited control patients.. Patients included in the educated group were younger, had an earlier detection of diabetes, and had better baseline glycemic control. Changes of HbA1c levels in the control and educated group arms were -1.41% and -1.23%, (p = 0.277) and the changes of fasting blood glucose levels were -1.89 mmol/L and -1.88 mmol/L (p = 0.854) in the control and educated groups, respectively. The changes in postprandial glucose levels were significantly greater in the control group (-2.88 mmol/L vs. -2.26 mmol/L in the educated group, p = 0.010). Body mass index in the control group did not actually change between baseline and end of study, but it decreased significantly in the educated group. In the educated group the number of self-monitoring days and the patients' physical activity increased between education sessions 1 and 3.. The possible reason for baseline differences between the two groups was that younger and more motivated patients with better glycemic control tended to join the education program. Education was associated with beneficial body mass changes but not with improvement in glycemic status. Improved self-monitoring and physical activity can be documented in the group of educated patients.. Bevezetés: A 2-es típusú cukorbetegség kezelésében a gyógyszeres kezelés mellett döntő jelentősége van a betegoktatásnak. Célkitűzés: A szerzők arra a kérdésre kerestek választ, hogy a 2-es típusú diabetesben szenvedő betegeknek nyújtott csoportos edukáció fejt-e ki pozitív addicionális hatást a cukorháztartásukra és életvezetésük egyes jellemzőire. Módszer: A beavatkozással nem járó vizsgálatba 18–75 év közötti betegeket vontak be. Az edukált betegeket a betegedukációt biztosító centrumok, a kontrollbetegeket a hagyományos cukorbeteg-tanácsadást végző centrumok vonták be a vizsgálatba. Eredmények: Kiinduláskor az edukációs csoport betegei fiatalabbak voltak, rövidebb volt a diabetesanamnézisük és jobb vércukorháztartással rendelkeztek. A kontroll- és az edukációs csoportban a HbA1c változása –1,41% vs. –1,23% (p = 0,277), az éhomi vércukorszinté –1,89 mmol/l vs. –1,88 mmol/l (p = 0,854) volt. A postprandialis vércukorszintben a kontrollcsoportban lehetett szignifikánsan nagyobb csökkenést kimutatni: (–2,88 mmol/l vs. –2,26 mmol/l; p = 0,010). A kontrollcsoport betegeinek testtömegindex-értéke lényegében változatlan maradt, míg az edukációs csoporté szignifikánsan csökkent. Az edukációs csoportban az 1. és a 3. edukációs alkalom között nőtt az önellenőrzési napok száma és a betegek fizikai aktivitása. Következtetések: Az induláskor meglévő különbségek valószínű magyarázata, hogy az edukációs csoportokba a fiatalabb, motiváltabb, jobb anyagcsere-állapotban lévő betegek léptek be. Az edukáció a vércukorháztartásban nem, de a testtömegindexben kedvező változással járt együtt. Az edukált betegek körében javuló önellenőrzési aktivitást és több testmozgást lehetett kimutatni. Orv. Hetil., 2014, 155(43), 1713–1721.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Life Style; Male; Middle Aged; Motor Activity; Patient Education as Topic; Treatment Outcome

The management of type 2 diabetes mellitus in long-term care (LTC) settings can be complex as a result of age-related complications. Despite guideline recommendations, sliding scale insulin remains commonplace in the LTC setting and data on basal insulin use are lacking.. This retrospective study used medical chart data and the Minimum Data Set from elderly LTC facility patients who received basal insulin (insulin glargine, insulin detemir, or neutral protamine Hagedorn insulin) for the treatment of diabetes, to investigate the practice patterns and associated clinical outcomes.. A total of 2,096 elderly, insulin-treated patients in LTC were identified, with 59.5% of them (N=1,247) receiving basal insulin. Of these, more than 50% of patients received sliding scale insulin in co-administration with basal insulin. Despite its ease of use, insulin pen use was very low, at 14.6%. Significant differences were observed between the basal insulin groups for glycated hemoglobin level and dosing frequency. Hypoglycemia was uncommon -17.2% of patients experienced at least one event, and there was no significant difference in the prevalence of hypoglycemia between the groups.. These data suggest the underutilization of basal insulin in the LTC setting and worryingly high combinational use with sliding scale insulin. Differences in glycated hemoglobin and dosing frequencies between types of basal insulin warrant further comparative effectiveness studies.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug Utilization; Female; Glycated Hemoglobin; Homes for the Aged; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Nursing Homes; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors

An increase in body weight is a commonly perceived effect of insulin therapy for type 2 diabetes mellitus, and this may serve as a barrier to insulin initiation and usage.. To investigate the baseline clinical and demographic factors associated with weight gain during insulin glargine therapy, and the implications of weight change on clinical outcomes.. This was a retrospective analysis of patient-level data from phase 3 or 4 randomized controlled, treat-to-target (fasting plasma glucose [FPG] ≤ 100 mg/dL) trials evaluating basal insulin glargine for ≥ 24 weeks. The Pearson correlation coefficient and Cochran-Armitage trend statistic were used to calculate the existence of a trend between absolute and relative weight change, and relative glycated hemoglobin (HbA1c) change from baseline; likelihood of achieving target HbA1c < 7.0%; change from baseline FPG; insulin dose requirements; incidence of hypoglycemia; and adverse events.. Eleven studies were included, encompassing a total of 2140 patients. Patients starting insulin glargine treatment gained a mean ± standard deviation 1.8 ± 3.7 kg (4.0 ± 8.2 lb). Most patients had limited weight change (± 2.5 kg or 5.5 lb). Younger age, higher baseline HbA1c, and higher baseline FPG were predictive of greater weight gain (P < 0.0001). Those who gained more weight experienced the largest decrease from baseline in HbA1c and FPG. More weight gain was associated with higher insulin dose requirements, an increased risk of experiencing either symptomatic or glucose-confirmed (< 70 mg/dL) hypoglycemia, and more adverse events. Older patients (> 65 years) were less likely to gain weight or to experience glucose-confirmed hypoglycemia, but more likely to experience severe hypoglycemia.. In this retrospective analysis of patient-level data, most patients had a stable weight (defined as ± 2.5 kg) after 24 weeks of insulin glargine, and weight gain varied with patient demographics. Therefore, insulin glargine can be used in these patient groups with type 2 diabetes without expectation of significant weight gain.

Topics: Adolescent; Adult; Age Factors; Aged; Blood Glucose; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Weight Gain; Young Adult

Neonatal diabetes mellitus (NDM) results from impaired insulin secretion, occurring within the first 6 months of life. NDM is classified as transient NDM (TNDM) or permanent NDM. To date there are no universal guidelines regarding its management. Intravenous insulin infusion represents the first and most adequate therapeutic approach for sustained hyperglycemia, but this can provide only a short-term solution. Several factors should be taken into account in the choice of the long-term treatment. We describe our experience with two infants affected by TNDM. The first child was treated with continuous subcutaneous insulin infusion, whereas the second infant was treated with subcutaneous insulin glargine injections. Our experience shows that the two different therapeutic approaches, if properly managed, are equally effective.

Topics: Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Italy; Precision Medicine; Treatment Outcome

Topics: Adult; Drug Overdose; Female; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Suicide, Attempted; Time Factors

Within longitudinal epidemiological research, 'count' outcome variables with an excess of zeros frequently occur. Although these outcomes are frequently analysed with a linear mixed model, or a Poisson mixed model, a two-part mixed model would be better in analysing outcome variables with an excess of zeros. Therefore, objective of this paper was to introduce the relatively 'new' method of two-part joint regression modelling in longitudinal data analysis for outcome variables with an excess of zeros, and to compare the performance of this method to current approaches.. Within an observational longitudinal dataset, we compared three techniques; two 'standard' approaches (a linear mixed model, and a Poisson mixed model), and a two-part joint mixed model (a binomial/Poisson mixed distribution model), including random intercepts and random slopes. Model fit indicators, and differences between predicted and observed values were used for comparisons. The analyses were performed with STATA using the GLLAMM procedure.. Regarding the random intercept models, the two-part joint mixed model (binomial/Poisson) performed best. Adding random slopes for time to the models changed the sign of the regression coefficient for both the Poisson mixed model and the two-part joint mixed model (binomial/Poisson) and resulted into a much better fit.. This paper showed that a two-part joint mixed model is a more appropriate method to analyse longitudinal data with an excess of zeros compared to a linear mixed model and a Poisson mixed model. However, in a model with random slopes for time a Poisson mixed model also performed remarkably well.

Topics: Binomial Distribution; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Longitudinal Studies; Models, Statistical; Poisson Distribution

Intentional insulin glargine overdose is rarely reported in the literature, but usually results in prolonged hypoglycemia requiring intensive care unit admission.. We report a case of using octreotide to treat prolonged hypoglycemia after a large insulin glargine overdose.. A 56-year-old man with type 2 diabetes mellitus presented to the Emergency Department after a multidrug overdose including up to 3,300 units insulin glargine. He required admission to the intensive care unit for mechanical ventilation and blood-glucose monitoring every 30 to 60 min. He received a continuous dextrose infusion for >100 h for persistent hypoglycemia. Octreotide, a somatostatin analogue, was given on day 4 of admission in an attempt to inhibit any insulin secretion from the pancreas that might be occurring in response to the dextrose infusion and to minimize the amount of fluid being given. After three doses, improvements in the patient's blood glucoses were seen, however, this could have coincided with complete absorption of the insulin.. Prolonged hypoglycemia often occurs after large overdoses of insulin glargine due to a depot effect at the site of injection. Octreotide is a potential adjunctive treatment to dextrose in patients with a functioning pancreas.

Topics: Drug Overdose; Gastrointestinal Agents; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Octreotide; Treatment Outcome

The Somogyi effect postulates that nocturnal hypoglycaemia causes fasting hyperglycaemia attributable to counter-regulatory hormone release. Although most published evidence has failed to support this hypothesis, this concept remains firmly embedded in clinical practice and often prevents patients and professionals from optimizing overnight insulin. Previous observational data found lower fasting glucose was associated with nocturnal hypoglycaemia, but did not assess the probability of infrequent individual episodes of rebound hypoglycaemia. We analysed continuous glucose monitoring data to explore its prevalence.. We analysed data from 89 patients with Type 1 diabetes who participated in the UK Hypoglycaemia study. We compared fasting capillary glucose following nights with and without nocturnal hypoglycaemia (sensor glucose < 3.5 mmol/l).. Fasting capillary blood glucose was lower after nights with hypoglycaemia than without [5.5 (3.0) vs. 14.5 (4.5) mmol/l, P < 0.0001], and was lower on nights with more severe nocturnal hypoglycaemia [5.5 (3.0) vs. 8.2 (2.3) mmol/l; P = 0.018 on nights with nadir sensor glucose of < 2.2 mmol/l vs. 3.5 mmol/l]. There were only two instances of fasting capillary blood glucose > 10 mmol/l after nocturnal hypoglycaemia, both after likely treatment of the episode. When fasting capillary blood glucose is < 5 mmol/l, there was evidence of nocturnal hypoglycaemia on 94% of nights.. Our data indicate that, in clinical practice, the Somogyi effect is rare. Fasting capillary blood glucose ≤ 5 mmol/l appears an important indicator of preceding silent nocturnal hypoglycaemia.

Topics: Adult; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Circadian Rhythm; Cohort Studies; Diabetes Mellitus, Type 1; Drug Monitoring; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Monitoring, Ambulatory; Prevalence; Severity of Illness Index; United Kingdom

To evaluate outcomes in insulin-naive patients with type 2 diabetes mellitus (T2DM) who initiated insulin glargine or insulin detemir.. Retrospective data were analyzed from the US General Electric Centricity electronic medical records (EMR) database from patients (≥18 years old) with T2DM initiating insulin glargine or detemir between January 1, 2006, and December 31, 2010. Included patients had EMR data for ≥6 months prior to (baseline) and ≥12 months after (follow-up) the index date (date of first insulin prescription), and at least one OAD and/or GLP-1 receptor agonist prescription order during baseline, but no previous insulin prescription. Patients were matched on baseline characteristics 5:1, insulin glargine to detemir, to ameliorate selection bias. Outcomes assessed were persistence with insulin therapy, glycemic control, hypoglycemia, body weight, and body mass index over follow-up.. Insulin glargine and detemir groups were similar in terms of gender (51.0% and 51.5% female, P = 0.7356), age (57.8 and 57.4 years, P = 0.3368), A1C (9.4% and 9.4%, P = 0.6642), and body weight (101.9 kg and 102.4 kg, P = 0.4920) at baseline. During follow-up, patients initiating insulin glargine were more persistent (80.1% vs 67.8%, P < 0.0001) and had a greater change in A1C (-1.11% vs -0.96%, P = 0.0479). Percentage change in weight (0.91% and 0.65%, P = 0.2734) and hypoglycemia prevalence (3.6% vs 4.1%, P = 0.4338) were similar between groups.. Results from this real-world EMR analysis suggest that among T2DM patients, initiating insulin treatment with insulin glargine may be associated with better treatment persistence and glycemic control, with similar prevalence of hypoglycemia and weight change, compared with initiating with insulin detemir. This study is limited by the retrospective nature of the data collection using EMRs and inability to confirm accuracy and completeness of data by secondary chart review.

Topics: Aged; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; United States

To evaluate the real-world rates of hypoglycemia and related costs among patients with type 2 diabetes mellitus (T2DM) who initiated insulin glargine with either a disposable pen or vial-and-syringe.. Pooled data were evaluated from six previously published, retrospective, observational studies using US health plan insurance claims databases to investigate adults with T2DM who initiated insulin glargine. The current study evaluated baseline characteristics, hypoglycemic events, and costs during the 6 months prior to and 12 months following insulin glargine initiation. Comparisons were made between patients initiating treatment with a disposable pen (GLA-P) and vial-and-syringe (GLA-V). Multivariate analyses using baseline characteristics as covariates determined predictors of hypoglycemia after initiating insulin glargine.. This study included 23,098 patients (GLA-P: 14,911; GLA-V: 8187). Overall annual prevalence of hypoglycemia was low (6.3% overall, 2.2% related to hospital admission or emergency department visit). Prevalence was significantly lower with GLA-P (5.5% vs 7.7%; p < 0.0001). Furthermore, average glycated hemoglobin HbA1c reduction was higher with GLA-P (-1.22% vs -0.86%; p = 0.0012). The average annual hypoglycemia-related cost associated with initiating insulin glargine was $293, with GLA-P being 46% lower than GLA-V ($225 vs $417; p = 0.001). Patients who had already developed microvascular complications at the time of initiating insulin therapy were at higher risk for developing hypoglycemia.. This study is limited by the use of retrospective data and ICD-9-CM codes, which are subject to coding error. In addition, this pooled analysis used unmatched cohorts, with multivariate regression analyses employed to adjust for between-group differences. Finally, results describe a managed care sample and cannot be generalized to all patients with T2DM.. Patients with T2DM initiating insulin glargine treatment showed low rates of hypoglycemia, especially when using a disposable pen device. Hypoglycemia-related costs were low, contributing a very small proportion to overall diabetes-related healthcare costs.

Topics: Adult; Aged; Blood Glucose; Cost Savings; Cost-Benefit Analysis; Databases, Factual; Diabetes Mellitus, Type 2; Disposable Equipment; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Costs; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Injections, Subcutaneous; Insulin Glargine; Insulin, Long-Acting; Logistic Models; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Retrospective Studies; Severity of Illness Index; Syringes

Topics: Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male

Insulin overdose can cause harm due to hypoglycaemia, effects on electrolytes and acute hepatic injury. The established long-acting insulin analogue preparations (detemir and glargine) can present specific management problems because, in overdose, their effects are extremely prolonged, often lasting 48-96 hours. The primary treatment is continuous intravenous 10% or 20% glucose infusion with frequent capillary blood glucose monitoring. Surgical excision of the insulin injection site has been used successfully, even days after the overdose occurred. Once the effects of overdose have receded, diabetes treatment must be restarted with care, especially in patients with type 1 diabetes. Monitoring serum insulin concentration has been successfully used to predict when the effects of the overdose will cease.

Topics: Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Drug Overdose; Electrolytes; Glucose; Humans; Hypoglycemia; Infusions, Intravenous; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Sweetening Agents

To evaluate the annual cost-utility of insulin degludec compared with glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2D-BOT), and type 2 diabetes receiving basal-bolus therapy (T2B-BB) in Sweden.. A cost-utility model was programmed in Microsoft Excel to evaluate clinical and economic outcomes. The clinical trials were designed as treat-to-target, with insulin doses adjusted in order to achieve similar glycemic control between treatments, thus long-term modeling is not meaningful. Basal and bolus insulin doses, incidence of hypoglycemic events, frequency of self-monitoring of blood glucose, and possibility for flexibility in timing of dose administration were specified for each insulin in three diabetes populations, based on data collected in Swedish patients with diabetes and a meta-analysis of clinical trials with degludec. Using these characteristics, the model estimated costs from a societal perspective and quality-adjusted life years (QALYs) in the two scenarios.. Use of degludec was associated with a QALY gain compared with glargine in T1D (0.31 vs 0.26 QALYs), T2D-BOT (0.76 vs 0.69 QALYs), and T2D-BB (0.56 vs 0.47 QALYs), driven by reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration. Therapy regimens containing degludec were associated with increased costs compared to glargine-based regimens, driven by the increased pharmacy cost of basal insulin, but partially offset by other cost savings. Based on estimates of cost and clinical outcomes, degludec was associated with incremental cost-effectiveness ratios of SEK 19,766 per QALY gained, SEK 10,082 per QALY gained, and SEK 36,074 per QALY gained in T1D, T2-BOT, and T2-BB, respectively.. The hypoglycemic event rates in the base case analysis were derived from a questionnaire-based study that relied on patient interpretation and recall of hypoglycemic symptoms. The relative rates of hypoglycemia with degludec compared to glargine were derived from a meta-analysis of phase III trials, which may not reflect the relative rates observed in real-world clinical practice. Both of these key limitations were explored in one-way sensitivity analyses.. Based on reduced incidence of hypoglycemia and possibility for flexibility around timing of dose administration, use of degludec is likely to be cost-effective compared to glargine from a societal perspective in T1D, T2-BOT, and T2-BB in Sweden over a 1-year time horizon.

Topics: Cost of Illness; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Models, Economic; Quality-Adjusted Life Years; Sweden

Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study.. Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables.. The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6-32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5-17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9-55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI -10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2-42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1-25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine.. There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice.

Topics: Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Coma; Female; Finland; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Medical Record Linkage; Poisson Distribution; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk

For patients with type 2 diabetes who are uncontrolled on a combination of two oral antidiabetic agents, addition of the long-acting basal insulin glargine is a well established treatment option. However, data on the efficacy and safety of a combination of metformin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and insulin glargine are limited in real-world settings. Therefore, the aim of this study was to analyze blood glucose control, rates of hypoglycemia and body weight in a large cohort of patients with type 2 diabetes treated with this combination therapy in real practice.. This noninterventional, multicenter, prospective, observational trial with a follow-up of 20 weeks enrolled insulin-naïve patients who had been on a stable fixed dose of metformin and a DPP-4 inhibitor for at least 3 months, and had a glycosylated hemoglobin (HbA1c) between 7.5% and 10%. Patients were selected at the investigators' discretion for initiation of insulin glargine at baseline. A total of 1,483 patients were included, of whom 1,262 were considered to be the efficacy set. Primary efficacy parameters were HbA1c and fasting plasma glucose. Secondary outcome measures included achievement of glycemic targets, body weight, rates of hypoglycemia, and other safety parameters, as well as resource consumption.. Upon initiation of insulin glargine, mean HbA1c decreased from 8.51% to 7.36% (-1.15%±0.91%; 95% confidence interval [CI] -1.20 to -1.10). An HbA1c level<6.5% was achieved in 8.2% of patients and a level<7.0% in 31.5%. Mean fasting plasma glucose decreased from 174±47 mg/dL to 127±31 mg/dL (-47.3±44.1 mg/dL; 95% CI -49.8 to -44.8). In 11.9% of patients, a fasting plasma glucose level<100 mg/dL was achieved. Bodyweight decreased on average by 0.98±3.90 kg (95% CI 1.19-0.76). Hypoglycemia (blood glucose≤70 mg/dL) was observed in 29 patients (2.30%), of whom six (0.48%) had nocturnal hypoglycemia and four (0.32%) had documented severe events (blood glucose<56 mg/dL).. The results of this observational study show that insulin glargine, when added to a fixed-dose combination of metformin and a DPP-4 inhibitor, resulted in a significant and clinically relevant improvement of glycemic control. Importantly, this intervention did not interfere with the action of the DPP-4 inhibitors, resulting in neutral effects on weight and low rates of hypoglycemia. We conclude that this treatment intensification approach may be useful, efficient, and safe in daily clinical practice for patients with type 2 diabetes.

Topics: Aged; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Combinations; Drug Therapy, Combination; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome

Monitoring efficacy of insulin glargine administered to patients with diabetes mellitus type 2 (DMT2) in combination with rapid-action insulin and analogues, where the hitherto fixed-mixture insulin therapy failed to achieve a satisfactory glycaemic control (HbA1c < 7%) following a six-month fixed-mixture insulin therapy.. Open, observational, multicentric, non comparative, prospective product registry.. 9-month prospective observational study recruited DMT2 patients previously uncontrolled on premixed insulin (HbA1c > 7%). Total of 278 subjects were documented in the study. At 9 months of follow-up 45,3% of patients reached a target HbA1c level <7% with a mean HbA1c change from 9.63 +/- 1.64% to 7.10 +/- 0.77% (p<0.01). Fasting plasma glucose values decreased from 12.7 +/- 4.3 mmol/L to 6.6 +/- 1.4 mmol/L (p<0,01). 93 patients (33,4%) experienced hypoglycemia events (3(1) hypoglycemic episode). Insulin glargine mean starting dose was 32,4 +/- 11,5 U. This dose was increased progressively over the study visits to a final mean dose of 42,0 +/- 11,9 U (p<0.01). The mean final daily dose of rapid-acting insulin was 24.8 +/- 13.7 U and was almost unchanged during the study. Patients who did not adhere to treatment were 4.9 times more likely to fail to achieve target HbA1c level (RR [95%CI] = 4.9 [1.7-12.11, p<0.01).. Results from the study suggest that basal-bolus regimen consisting of insulin glargine significantly improves glycaemic control without increasing hypoglycemia risk in DMT2 population with inadequate glycaemic control on previous premixed therapy.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

A 26-year-old man with Type 1 diabetes presented with an overdose of 4800 units of the long-acting insulin analogue, glargine (Lantus). Glucose supplementation of approximately 800 g/day was associated with acute hepatic injury.. On day 4, a depot of insulin was excised from the patient's abdominal wall; this was followed by a reduction in his glucose requirements and improvement in liver function.. This report highlights the risk of acute hepatic injury during the treatment of insulin overdose and the importance of careful glucose supplementation. It also demonstrates how earlier excision of an insulin depot could potentially prevent this problem and hasten recovery.

Topics: Abdomen; Adult; Device Removal; Diabetes Mellitus, Type 1; Drug Overdose; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Liver; Male; Treatment Outcome

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for patients with type 2 diabetes (T2DM). Tight glycaemic control immediately after RYGB for T2DM may improve long-term glycaemic outcomes, but is also associated with a higher risk of hypoglycaemia. We designed a treatment algorithm to achieve optimal glycaemic control in patients with insulin-treated T2DM after RYGB and evaluated its feasibility, safety and efficacy.. Fifty patients following protocol-driven diabetes management were discharged on a fixed amount of metformin and glargine, with the insulin dose adjusted according to a standardised insulin sliding scale aiming for a fasting capillary glucose (FCG) of 5.5-6.9 mmol/L. Glycaemic outcome and remission of diabetes (defined as HbA1c < 6% and FCG levels < 5.6 mmol/L for at least 1 year without hypoglycaemic medication) were compared between patients who received protocol-driven treatment and a similar cohort of 49 patients following standard glycaemic management.. At 1 year follow-up, the protocol-driven group showed a greater improvement in glycaemic control than the non-protocol-driven group (HbA1c -3.0 ± 0.2% vs. -1.2 ± 0.1%, P < 0.001; FCG levels -3.4 ± 0.2 vs. -2.0 ± 0.2 mmol/L, P = 0.02) and a higher remission rate from T2DM (50.0% vs. 6.1%, P < 0.001). No symptomatic hypoglycaemia was reported in either group.. The protocol-driven management proved to be feasible, safe and effective in achieving targeted glycaemic control in T2DM after RYGB. The next step will be to scrutinise the efficacy of protocol-driven management in a randomised controlled clinical trial.

Topics: Adolescent; Adult; Aged; Algorithms; Blood Glucose; Clinical Protocols; Cohort Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Feasibility Studies; Female; Follow-Up Studies; Gastric Bypass; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Postoperative Period; Young Adult

We evaluated the effectiveness of insulin glargine (glargine)-based regimens in patients with type 2 diabetes mellitus (T2DM) in clinical practice in Spain.. This was a retrospective, registry-based study of 1482 patients treated with neutral protamine Hagedorn (NPH) who were either switched to glargine or maintained on NPH at investigators' discretion. The primary outcomes were HbA(1c) change over a period of 4-9 months follow-up and incidence of hypoglycaemia.. Prior to switching treatment, mean ± standard deviation HbA(1c) was worse in the glargine vs. the NPH group (8.3 ± 1.2% vs. 7.9 ± 1.1% respectively; p < 0.0001). After 4-9 months of treatment, mean reductions in HbA(1c) were greater with glargine vs. NPH (-1.0 ± 1.0% vs. -0.2 ± 0.8% respectively; p < 0.0001) and the incidence of hypoglycaemia in the month prior to the study visit was lower (21.8% vs. 47.6% respectively; p < 0.0001). An expected reduction in dosing frequency, as well as in the basal insulin dose was reported for glargine vs. NPH, with 97.3% of glargine-treated patients on once-daily injections and 81.2% on NPH receiving twice-daily therapy. Improvements in treatment satisfaction were significantly higher with glargine (p < 0.0001).. In a Spanish clinical practice setting, patients with T2DM who switched to glargine from NPH experienced significantly greater reductions in mean HbA(1c) and a lower incidence of hypoglycaemia than patients maintained on NPH.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

Endpoint HbA(1c) <7.0% was achieved by 80 (73.4%) lispro mix 25 (LM25)-treated patients and 67 (60.9%) glargine-treated patients (p=0.027) with baseline 1,5 anhydroglucitol (1,5AG) below median and 75 (70.8%) LM25-treated patients and 72 (63.7%) glargine-treated patients (p=0.238) with 1,5AG≥median, suggesting, 1,5AG may offer therapeutic insight when starting insulin therapy.

Topics: Blood Glucose; Deoxyglucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

Topics: Administration, Oral; Blood Glucose; Child; Depressive Disorder; Disease Management; Female; Glucose; Humans; Hypoglycemia; Hypokalemia; Infusions, Intravenous; Injections, Subcutaneous; Insulin Glargine; Insulin, Long-Acting; Self Mutilation; Starch; Suicide, Attempted

Insulin glargine is a relatively new medication in the treatment of diabetes mellitus, and there have only been six case reports of overdoses in the literature with this specific insulin.. We present a unique case of insulin glargine overdose that presented with persistent hypoglycemia and required prolonged in-hospital treatment.. A 51-year-old woman with insulin-dependent diabetes and a history of suicide attempts by medication overdose presented to the Emergency Department the morning after she had self-administered 2700 units of her insulin glargine in an attempted suicide. She was treated with continuous intravenous dextrose infusion with liberal oral intake, and continued to have recurrent hypoglycemic episodes 96 h into her hospital stay. She was discharged on hospital day 5 after psychiatric clearance without any permanent complications.. A single massive overdose of insulin glargine can present with prolonged hypoglycemia. Emergency physicians should have a low threshold for initiating continuous dextrose infusions and admitting these patients for frequent blood glucose and serum electrolyte monitoring, preferably in an intensive care setting.

Topics: Diabetes Mellitus; Drug Overdose; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Suicide, Attempted

this study reports on the effectiveness of sitagliptin in Asian Indian type 2 diabetes patients seen at a tertiary diabetes care center who had inadequate glycemic control with oral hypoglycemic agents either alone or in combination, compared to a group of patients who received insulin glargine.. patients with type 2 diabetes mellitus (n = 2,817) whose glycemia was not controlled adequately (glycated hemoglobin >6.5%) with oral hypoglycemic agents (either alone or in combination) received oral sitagliptin 100 mg once daily in addition to existing therapy for a period of 24 weeks. Patients who received insulin glargine as add-on therapy (n = 2,743) served as the reference group. Data analysis included glycated hemoglobin, fasting plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia.. significant reductions in glycated hemoglobin and fasting plasma glucose values were noted after 24 weeks of additional sitagliptin therapy that were comparable to those with insulin glargine. While sitagliptin addition resulted in a small weight loss (0.3 kg), insulin glargine addition resulted in a weight gain (0.7 kg). The overall incidence of adverse experiences was low and generally mild in both groups.. in a large group of Asian Indian type 2 diabetes patients seen at a tertiary diabetes center in whom glycemia was not controlled adequately by oral hypoglycemic agents (either alone or in combination), addition of sitagliptin helped to achieve glycemic control to a similar extent as insulin glargine but with a marginal weight advantage.

Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemia; India; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Pyrazines; Retrospective Studies; Sitagliptin Phosphate; Statistics, Nonparametric; Triazoles; Triglycerides

The objective of this study was to evaluate the short-term and long-term clinical and economic outcomes associated with insulin glargine or NPH insulin in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with oral anti-diabetic drugs in Switzerland, modeling the interaction between hypoglycemia and glycemic control (HbA1c).. A validated discrete event simulation model for T2DM was used to predict incidence of short-term complications (symptomatic, nocturnal and severe hypoglycemic events) and long-term complications (microvascular and macrovascular events), life expectancy, quality-adjusted life years (QALYs) and direct medical costs in patients treated with insulin glargine or NPH insulin. The model was populated with published Swiss patient characteristics with T2DM. Baseline risks of hypoglycemic events, utility decrements of diabetes-related long-term complications and the hypoglycemia fear score were derived from the literature. Relative risk reductions of hypoglycemia adjusted for HbA1c using insulin glargine compared with NPH insulin were based on a published negative binomial meta-regression analysis. Costs of severe hypoglycemia, micro- and macrovascular events were analyzed from literature whenever possible otherwise guideline-projected resource-use estimations were valued with Swiss official prices or tariffs in 2006 CHF. Simulations were run with 1,000 patients per cohort over a time horizon of 40 years. Incremental cost effectiveness ratios (ICERs) were presented as cost per QALY and per life year gained (LYG). Future costs and clinical benefits were discounted at 3.5%. Wide-range one-way sensitivity analyses were performed.. Insulin glargine was associated with an improvement in quality of life (0.098 QALYs per patient) and additional life expectancy (0.05 life years gained per patient) compared to NPH insulin. Incremental costs of CHF 2,578 resulted in an ICER of CHF 26,271 per QALY and CHF 51,100 per LYG. The cost per QALY was most sensitive to changes in costs, utility decrements and relative risk reductions of hypoglycemia.. This study evaluated, for the first time, the cost effectiveness of insulin glargine versus NPH insulin for the treatment of T2DM considering the interaction between glycemic control and hypoglycemia in Switzerland. The base case and sensitivity analyses demonstrated that insulin glargine proved to be cost-effective with respect to accepted willingness to pay thresholds and therefore represents good value for money.

Topics: Aged; Computer Simulation; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Switzerland; Time Factors; Treatment Outcome

To compare 2-year glycaemic control, hypoglycaemia and healthcare expenditures following insulin glargine (glargine, n = 2105) or neutral protamine Hagedorn (NPH) insulin (NPH, n = 734) initiation in patients with type 2 diabetes (T2D).. Retrospective cohort study using an integrated US health insurance administrative database was conducted. Individuals with a diabetes diagnostic claim and initiated basal insulin therapy with glargine or NPH from 2001 to 2005 dispensed at least one oral antidiabetic drug prescription during 6 months prior to basal insulin initiation and enrolled in the same health insurance plan from 6 months before to 12 months or more after insulin initiation were identified. Repeated measures mixed-effects models evaluated glycaemic and financial outcomes to account for factors potentially contributing to selection of insulin therapy, that is, age, gender, baseline HbA1c level, health expenditures, co-morbidities, healthcare utilization, pharmacy co-payment and follow-up antidiabetic medications.. Adjusted mean HbA1c value in the first year following insulin initiation was significantly lower for glargine versus NPH initiators (Δ = -0.43, p = 0.006); this difference diminished in the second year (Δ = -0.16, p = 0.375). First-year adjusted quarterly hypoglycaemia incidence rates were lower for glargine (2.1%) versus NPH (2.4%) (p = 0.02) as was the second-year quarterly rate (1.8 vs. 2.2%; p = 0.01). Both the first- and second-year adjusted total healthcare expenditures were lower in the glargine versus NPH group (year 1: $18,720 vs. $19,996, p = 0.005; year 2: $15,008 vs. $17,336; p < 0.001).. Glargine therapy may be an effective long-term option for improving glycaemic control, with lower rates of hypoglycaemia and healthcare costs in patients with T2D.

Topics: Blood Glucose; Cohort Studies; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States

Insulin therapy is recommended for patients with type 2 diabetes mellitus and an initial A1C level greater than 9 percent, or if diabetes is uncontrolled despite optimal oral glycemic therapy. Insulin therapy may be initiated as augmentation, starting at 0.3 unit per kg, or as replacement, starting at 0.6 to 1.0 unit per kg. When using replacement therapy, 50 percent of the total daily insulin dose is given as basal, and 50 percent as bolus, divided up before breakfast, lunch, and dinner. Augmentation therapy can include basal or bolus insulin. Replacement therapy includes basal-bolus insulin and correction or premixed insulin. Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing therapy. Metformin should be continued if possible because it is proven to reduce all-cause mortality and cardiovascular events in overweight patients with diabetes. In a study comparing premixed, bolus, and basal insulin, hypoglycemia was more common with premixed and bolus insulin, and weight gain was more common with bolus insulin. Titration of insulin over time is critical to improving glycemic control and preventing diabetes-related complications.

Topics: Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Family Practice; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Metformin; Pain; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain

Real-world data comparing outcomes of type 2 diabetes mellitus (T2DM) patients initiating different insulin regimens can help with treatment decisions and patient management. Clinical and economic outcomes following initiation with insulin glargine disposable pen (GLA-P) or insulin detemir disposable pen (DET-P) in T2DM patients were compared over 1-year follow-up.. This retrospective cohort analysis was conducted on data in a US national managed care claims database (July 2006 to September 2010) from patients initiating insulin treatment with GLA-P or DET-P. Treatment persistence, adherence, glycated hemoglobin (A1C), hypoglycemic events, and healthcare costs during follow-up were compared.. In all, 1682 patients were identified; 1016 (60.4%) started using GLA-P, 666 (39.6%) started using DET-P. After 1:1 propensity score matching, each cohort comprised 640 patients. Patients initiating GLA-P were significantly more likely to persist and adhere to treatment, and used a lower daily consumption dose. Over the last quarter of follow-up, fewer GLA-P users switched to DET-P compared with those switching from DET-P to GLA-P. GLA-P was associated with lower A1C levels and higher reduction of A1C levels from baseline, with no significant difference in the number of patients having hypoglycemic events. Patients in both cohorts had similar total and diabetes-related healthcare costs, but healthcare costs were lower in the GLA-P cohort for each 1% reduction in A1C from baseline.. This real-world study demonstrates that patients initiating GLA-P were more likely to persist with and adhere to treatment, with better glycemic control and similar overall hypoglycemia rate at no increase in healthcare cost.

Topics: Adult; Aged; Cohort Studies; Diabetes Mellitus, Type 2; Disposable Equipment; Drug Dosage Calculations; Drug Monitoring; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Outcome and Process Assessment, Health Care; Patient Preference; Retrospective Studies

Topics: Blood Glucose; Clinical Trials as Topic; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Despite significant advances in inpatient diabetes management, it is still a challenge to choose the safest and most efficacious subcutaneous insulin regimen for diabetic patients on continuous enteral nutrition (EN) therapy. The authors conducted a retrospective analysis of glycemic control in 22 non-critically ill diabetic patients, receiving at least 3 days of continuous EN. Patients received different insulin regimens while on continuous EN, including a basal/bolus glargine/lispro regimen (group 1, n = 8), 70/30 biphasic insulin twice daily (group 2, n = 8), and 70/30 biphasic insulin 3 times a day (group 3, n = 6). The glucose data from 72 hours from the initiation of EN were analyzed (12 point-of-contact glucose measurements per patient). Overall, the degree of control was comparable in all groups, with target range maintained more consistently in group 3 (70/30 insulin administered 3 times daily). In this group, 69% of values were in the target range (140-180 mg/dL) as compared with 24% in glargine/lispro group and 22% in the 70/30 insulin bid group. Eight hypoglycemic episodes occurred among the 3 groups: 5 episodes in group 1 (5.4%), 2 episodes in group 2 (2.1%), and 1 episode in group 3 (1.4%) (P = .05, groups 2 and 3 vs group 1). Administration of 70/30 biphasic insulin 3 times daily is a safe therapeutic regimen in diabetic patients on continuous EN as it maintains glycemia in the target range and might produce fewer episodes of hypoglycemia.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus; Dose-Response Relationship, Drug; Enteral Nutrition; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Middle Aged; Retrospective Studies; Young Adult

To compare total costs and risk of hypoglycemia in patients with type 2 diabetes (T2D) initiated on NPH insulin versus glargine in a real-world setting.. This study used claims data (10/2001 to 06/2005) from a privately insured U.S. population of adult T2D patients who were initiated on NPH or glargine following a 6-month insulin-free period. A sample of 1698 glargine-treated and 400 NPH-treated patients met the inclusion criteria. Total and diabetes-related costs (inflation-adjusted to 2006) were calculated for 6-month pre- and post-index periods and compared between 400 patient pairs matched by a propensity score method.. In the post-index 6-month period, glargine patients incurred higher diabetes-related drug costs than NPH patients ($785 versus $632, p<0.0001) but there were no significant differences in diabetes-related medical or total costs, or all other total cost categories. Compared to the pre-index period, glargine patient costs declined by $2420 (p=0.058) whereas NPH patient costs declined by $4200 (p=0.046), with no statistically significant group differences (p=0.469). Among patients with hypoglycemia-related claims (0.75% in both groups), mean hypoglycemia-related costs were $85 and $202 for NPH and glargine patients, respectively (p=0.564).. Initiation of either NPH or glargine was associated with major cost reductions and infrequent hypoglycemia-related claims.

Topics: Adult; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Therapy; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Selection; Probability; Propensity Score; Retrospective Studies; United States

Fasting during Ramadan is a major tenet of the Muslim religion. All adults after the age of puberty are required to do so if health permits. However, there are exemptions to this requirement and having a chronic condition such as diabetes is one. Nevertheless, many adults and adolescents feel obliged to fast during Ramadan even though there is no absolute need to do so. This obligation must be respected. There are few data to support this practice in those whose condition, such as diabetes, potentially makes them vulnerable to developing problems during prolonged fasting. This study was designed to examine the ability and safety of young people with diabetes to be able to fast if they so desire. Two groups of patients were studied, those on a multiple injection, so-called basal-bolus, regimen and those on a 'conventional' twice daily pre-mixed insulin regimen. All patients showed a tendency to high blood glucose at the time of commencing their fast. Those on twice daily insulin continued to have hyperglycaemia during the day whilst those on basal-bolus insulin showed a steady fall in blood glucose towards normal by the time of breaking their fast. Although there was a greater tendency to hypoglycaemia in the basal-bolus group, this could be successfully prevented by reducing the dose of basal insulin by 10-20%. We recommend that it is safe for adolescents with diabetes to fast during Ramadan as long as they reduce their basal insulin by this amount and continue to monitor their blood glucose regularly.

Topics: Adolescent; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Fasting; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Islam

Unexplained hypoglycemia in a pediatric diabetic patient can perplex even the savviest health care providers and lead to an extensive medical workup. We present here the cases of 2 children with type 1 diabetes mellitus treated with insulin pumps who were hospitalized for episodes of hypoglycemia. Review of their insulin pumps revealed normal basal and bolus insulin delivery. However, subsequent review of the priming history in the pump revealed that both children were receiving additional insulin under the manual-prime function, which is not included in the daily totals and, therefore, was initially unnoticed. Ultimately, both children confessed to surreptitiously using this priming function to self-administer extra insulin. It is important that health care professionals who are caring for diabetic patients be aware of this possibility.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diagnosis, Differential; Diet, Diabetic; Dose-Response Relationship, Drug; Emergency Service, Hospital; Equipment Design; Equipment Failure Analysis; Factitious Disorders; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin Infusion Systems; Insulin, Long-Acting; Male; Self Medication; Substance-Related Disorders

This article describes a patient with type 2 diabetes mellitus achieving glycemic control after transitioning from premixed to basal-prandial insulin.. A case report illustrates the challenges of achieving glycemic control in type 2 diabetes, and results of a literature search regarding premixed and basal-prandial insulins are presented.. A 52-year-old obese man with type 2 diabetes for 10 years initiated therapy with 2 oral antidiabetic drugs (OADs). When OAD therapy no longer maintained glycemic targets, and the addition of exenatide proved intolerable, he started premixed insulin aspart 70/30. However, lapses in exercise and irregular meal patterns led to a loss of glycemic control and nocturnal hypoglycemia. Switching to a basal-prandial regimen, starting with basal insulin glargine and then adding prandial insulin glulisine, subsequently resulted in a glycated hemoglobin level of 6.7%.. The patient benefited from the addition of 1 or more prandial insulin injections to a once-daily basal insulin analog.

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Obesity

This study reports on the effectiveness of exenatide compared to insulin glargine or NPH insulin in patients with type 2 diabetes mellitus, unable to achieve glycemic control with oral glucose-lowering therapies in a clinical care setting.. Patients with type 2 diabetes mellitus (n = 47) whose glycemia was not controlled adequately with oral hypoglycemic agents at maximum recommended therapeutic doses were initiated on exenatide therapy. Age-, sex-, and body mass index-matched patients receiving insulin glargine (n = 54) or NPH insulin (n = 23) served as controls. Data analysis included glycated hemoglobin, fasting and postprandial plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia.. A statistically significant reduction in glycated hemoglobin value was noted after initiating exenatide (pre-exenatide 9.7 +/- 1.4% vs. post-exenatide 8.7 +/- 1.5%; P < 0.05), which was comparable to values after insulin glargine (9.8 +/- 1.1% vs. 9.0 +/- 1.5%, respectively; P < 0.05) and NPH insulin (9.6 +/- 1.4% vs. 8.9 +/- 1.3%, respectively; P < 0.05). Exenatide therapy was associated with net weight loss (mean, 1.6 kg), but therapy with insulin glargine and NPH insulin was associated with weight gain (1.8 and 2.3 kg, respectively).. In a group of select Asian Indian type 2 diabetes patients with secondary failure to oral hypoglycemic agents seen at a diabetes center, exenatide treatment in combination with oral drug regimens resulted in significant lowering of glycated hemoglobin similar to insulin glargine or NPH insulin but with the additional benefit of weight loss, albeit a small amount.

Topics: Adult; Aged; Asian People; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Peptides; Surveys and Questionnaires; Treatment Outcome; Venoms

Insulin is normally added to oral glucose-lowering drugs in people with type 2 diabetes when glycaemic control becomes suboptimal. We evaluated outcomes in people starting insulin therapy with neutral protamine Hagedorn (NPH), detemir, glargine or premixed insulins.. Insulin-naïve people with type 2 diabetes (n = 8009), ≥ 35 years old, HbA(1c) ≥ 6.5% and begun on NPH (n = 1463), detemir (n = 357), glargine (n = 2197) or premix (n = 3992), were identified from a UK database of primary care records (The Health Improvement Network). Unadjusted and multivariate-adjusted analyses were conducted, with persistence of insulin therapy assessed by survival analysis.. In the study population (n = 4337), baseline HbA(1c) was 9.5 ± 1.6%, falling to 8.4 ± 1.5% over 12 months (change -1.1 ± 1.8%, p < 0.001). Compared with NPH, people taking detemir, glargine and premix had an adjusted reduction in HbA(1c) from baseline, of 0.00% (p = 0.99), 0.19% (p < 0.001) and 0.03% (p = 0.51). Body weight increased by 2.8 kg overall (p < 0.001), and by 2.3, 1.7, 1.9, and 3.3 kg on NPH, detemir, glargine and premix (p < 0.001 for all groups); insulin dose at 12 months was 0.70 (overall), 0.64, 0.61, 0.56 and 0.76 U/kg/day. After 36 months, 57% of people on NPH, 67% on glargine and 83% on premix remained on their initially prescribed insulin.. In routine clinical practice, people with type 2 diabetes commenced on NPH experienced a modest disadvantage in glycaemic control after 12 months compared with other insulins. When comparing the insulins, glargine achieved best HbA(1c) reduction, while premix showed greatest weight gain and the highest dose requirement, but had the best persistence of therapy.

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insulins; Male; Medication Adherence; Middle Aged; Treatment Outcome; Weight Gain; Young Adult

Aim of this prospective study is to evaluate the effect of repaglinide t.i.d. (three times a day) plus single-dose insulin glargine regimen in low-risk type 2 diabetic patients during Ramadan fasting. Participants had been taking the regimen for at least 3 months. Patients with a history of diabetic coma, severe hypoglycemic crisis or repeating attacks of hypoglycemia were excluded. Hypoglycemic unawareness, kidney or liver disease or HbA1c over 8% were also accepted as exclusion criteria. Eleven patients who insisted on this worship and eight non-fasting cases were involved. All were told to make home-glucose-monitorisation weekly and report any hypoglycemic event throughout Ramadan. Fasting blood glucose (FBG), post-prandial blood glucose (PBG) and fructosamine levels, body weights and blood pressures were recorded just before and after Ramadan. Seven patients in each group concluded the follow-up. Any significant change was detected in the parameters in either groups (P>0.05). Glucose control remained unchanged; fructosamine 318.14+/-65.38 versus 317.28+/-52.80 mmol/L in fasting group, 290.71+/-38.48 versus 290+/-38.56 mmol/L in non-fasting group. None of them exhibited either a major or a minor hypoglycemic event. The results of this pilot study indicated that repaglinide t.i.d. plus single-dose insulin glargine regimen was safe for low-risk type 2 diabetic patients who insisted on fasting during Ramadan.

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Blood Pressure; Carbamates; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Fructosamine; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Islam; Male; Middle Aged; Patient Selection; Piperidines; Risk Assessment; Safety; Turkey

We compared maternal and neonatal outcomes in diabetic pregnancies treated with either insulin glargine or neutral protamine Hagedorn (NPH) insulin. We performed a retrospective chart review of diabetic pregnant patients using the Diabetes Care Center of Wake Forest University during the years 2000 to 2005. Outcomes of interest included maternal hemoglobin A1C, average fasting and 2-hour postprandial blood sugars, mode of delivery, birth weight, 5-minute Apgar score < 7, umbilical artery pH < 7.20, incidence of neonatal hypoglycemia, and pregnancy complications. A total of 52 diabetic pregnant patients were included in this study. Twenty-seven women used insulin glargine. A total of 13 women used insulin glargine during the first trimester. Glycemic control was similar in women who used NPH insulin and insulin glargine, as determined by hemoglobin A1C levels and mean blood sugar values. There were no differences in mode of delivery, average birth weight, or neonatal outcomes. Maternal and fetal/neonatal outcomes appear similar in pregnant diabetic women who use either NPH insulin or insulin glargine in combination with a short-acting insulin analogue to achieve adequate glycemic control during pregnancy. Insulin glargine appears to be an effective insulin analogue for use in women whose pregnancies are complicated by diabetes.

Topics: Adult; Apgar Score; Birth Weight; Blood Glucose; Carbon Dioxide; Delivery, Obstetric; Diabetes, Gestational; Eating; Fasting; Female; Gestational Age; Glycated Hemoglobin; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Oxygen; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pregnancy Outcome; Retrospective Studies; Umbilical Arteries; Young Adult

Insulin glargine (glargine) and insulin NPH (NPH) are two basal insulin treatments. This study investigated the effect on glycaemic control of switching from a NPH-based regimen to a glargine-based regimen in 701 patients with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care data.. Data for this retrospective observational study were extracted from a UK primary care database (The Health Improvement Network). Patients were required to have at least 12 months of data before and after switching from NPH to glargine. The principal analysis was the change in HbA(1c) after 12 months treatment with glargine; secondary analyses included change in weight and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable reporting of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables.. After adjustment, both diabetic cohorts showed statistically significant reductions in mean HbA(1c) 12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with baseline HbA(1c); patients with baseline HbA(1c) > or = 8% had reductions of 0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant change in weight or total daily insulin dose while on glargine. The majority of patients received a basal-bolus regimen prior to and after the switch (mean 79.3% before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%, respectively in type 2 patients, p > 0.05).. In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.

Topics: Adult; Body Weight; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Young Adult

Examine real-world effectiveness and hypoglycemia cost burden in patients with type 2 diabetes newly initiated on exenatide or insulin glargine.. Retrospective cohort study describing patient characteristics, drug adherence patterns, and 1-year hypoglycemia rates with associated costs using an administrative claims database. Adult subjects with type 2 diabetes had an initial claim for exenatide or insulin glargine between May 1, 2005 and June 30, 2007, and had continuous eligibility for >or= 6 months pre- and >or= 12 months post-initiation.. The exenatide cohort (n = 3262) was 53 +/- 10 years (+/-SD); 54% female. The insulin glargine cohort (n = 3038) was 56 +/- 12 years; 41% female. The mean Deyo-Charlson comorbidity index score was 1.45 for exenatide versus 1.82 for insulin glargine (p < 0.001). Baseline OAD use rates for exenatide and insulin glargine, respectively, were 77% versus 69% metformin; 47% versus 65% sulfonylurea; 50% versus 49% thiazolidinedione; 56% versus 60% multiple OAD. For patients with two or more pharmacy claims for exenatide or insulin glargine, the 12-month medication possession ratio (MPR) was 68 +/- 29% for exenatide and 58 +/- 28% for insulin glargine (p < 0.001). MPR >or= 80% was higher for exenatide (p < 0.001) and fewer patients discontinued therapy (p < 0.001). The probability of a hypoglycemic event was significantly lower for exenatide (p < 0.005), resulting in lower associated annual costs.. This study provides the first real-world observational comparison of type 2 diabetes patients newly initiated on exenatide or insulin glargine. Exenatide patients had a lower comorbidity burden, better drug adherence, and a lower rate of hypoglycemic events with associated costs. Retrospective database analyses examine medical care utilization in large populations using a relatively inexpensive and expedient approach. However, data are only representative of a commercial health-care plan with limited information on multiple variables usually collected during clinical trials.

Topics: Aged; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Patient Compliance; Peptides; Retrospective Studies; Venoms

Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data.. Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables.. Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c > or = 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 +/- 1.35 U/Kg to 0.88 +/- 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 +/- 2.51 U/Kg to 0.98 +/- 2.58 U/Kg, p < 0.001).. In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.

Topics: Adult; Body Weight; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Family Practice; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Young Adult

Topics: Adult; Drug Overdose; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Glargine; Insulin, Long-Acting; Potassium; Suicide, Attempted

The insulin analogs, glargine and detemir, are associated with reduced hypoglycemia incidence compared with NPH insulin. We assessed the impact of changing basal insulin from NPH to glargine or detemir in patients with type 1 diabetes mellitus who experienced severe hypoglycemia.. A retrospective chart review was conducted that included 73 (31 female) patients (mean age 48 years, diabetes duration 19 years) treated for 12 to 24 months with insulin glargine (n = 43) or detemir (n = 30).. There were no patients who withdrew from treatment due to side effects. The mean treatment duration in both groups was 18 months. Changing from NPH insulin was associated with a -0.3% (p = 0.036) reduction in HbA1c for glargine (baseline 8.8%) and -0.4% (p = 0.040) for detemir (baseline 8.3%) treated patients; insulin dosages increased, respectively by 4.1 (p = 0.045) and 4.3 units (p = 0.004) (mean values). Weight did not increase significantly and the 1-year rate of serious hypoglycemia was 0.25/person/year.. Switching from NPH-insulin to insulin detemir or glargine in type 1 diabetes mellitus patients with previous serious hypoglycemia was associated with a reduction in HbA1c. However, severe hypoglycemia was not completely eliminated, and few patients reached internationally accepted glycemic treatment goals.. We searched Medline, PubMed (with key search terms type 1 diabetes, NPH insulin, detemir, glargine and serious hypoglycemia), reference lists and databases of ongoing and completed trials (through July 2008) provided from the manufacturers of the drugs to identify relevant literature.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Between 5 and 10% of the European population suffers from diabetes, and its prevalence is constantly rising, in Austria like in other countries. The main goals in the treatment of diabetes mellitus are the prevention of complications and organ damage, the prevention of severe hypo- and hyperglycaemia and the preservation of quality of life. Many patients with type 2 diabetes become insulin-dependent in the course of their disease. The application of a long acting insulin or insulin analogue is the simplest way of initiating an insulin therapy and is in accordance with current guidelines. Current scientific evidence shows that the use of long acting insulin analogues for type 2 diabetes; which can no longer be sufficiently controlled with oral antidiabetic agents, is simple, safe and efficacious. Thus, this treatment option should be available without any restrictions to physicians and patients in order to facilitate the beginning of an insulin regime. This position paper summarises up the current evidence concerning this subject.

Topics: Austria; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Myocardial Infarction; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Rosiglitazone; Thiazolidinediones

This article reevaluates the hypoglycemic episodes reported as severe in the Treat-to-Target Trial comparing insulin glargine and NPH insulin use in patients with inadequately controlled type 2 diabetes.. Case report forms from the Treat-to-Target Trial were reviewed to identify additional severe hypoglycemic events and to further characterize those events already identified. Severe hypoglycemia was defined as symptoms consistent with hypoglycemia requiring assistance of another person and associated with either glucose levels < or =56 mg/dL or prompt recovery after oral carbohydrate intake, intravenous glucose administration, or glucagon injection.. This analysis confirmed that severe hypoglycemia was similarly uncommon with both insulins (insulin glargine [n = 367], nine patients, 14 events; NPH insulin [n = 389], nine patients, 13 events); all hypoglycemic events for glargine and nine for NPH were treated effectively at home. All severe hypoglycemic episodes were associated with sulfonylurea use. A review of case report forms demonstrated inconsistencies in identification of severe hypoglycemia (seven of 14 severe events for glargine and three of 13 severe events for NPH were coded as moderate).. The rate of severe hypoglycemia in this trial was low. Difficulties in gathering and interpreting hypoglycemia data highlight the need for more objective methods.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Sulfonylurea Compounds

To determine the safety and efficacy of insulin glargine and glimepiride in patients with Type 2 diabetes before and after Ramadan and during fasting for Ramadan.. In this open, descriptive, multi-centre, prospective study, insulin-naïve (n = 100) or previously insulin-treated (n = 249) patients with Type 2 diabetes received insulin glargine [titrated from 10 U daily according to fasting blood glucose (FBG)] and glimepiride (4 mg daily). The number and type of hypoglycaemic episodes and glycaemic control were assessed before, during and after Ramadan. Bivariate logistic regression analyses were used to identify factors which predicted hypoglycaemia during Ramadan.. Only one episode of severe hypoglycaemia occurred in each time period before, during and after Ramadan. Mild hypoglycaemic episodes increased from 156 pre-Ramadan to 346 during Ramadan (P < 0.001) and decreased to 153 post-Ramadan (P = 0.0002).The increase during Ramadan was mainly attributed to increased symptomatic hypoglycaemic episodes. FBG and glycated haemoglobin improved during the titration period and did not change during the rest of the study. Risk of hypoglycaemic events during Ramadan was higher in countries where fasting is strict [odds ratio (OR) 3.69 (2.06-6.63), P < 0.0001]. Lower weight [< 70.0 kg; OR 2.56 (1.46-4.48), P = 0.001] and waist circumference [< 90 cm; OR 3.06 (1.62-5.78), P = 0.001] increased the risk of hypoglycaemia during Ramadan whilst FBG > 6.7 mmol/l [OR 0.3 (0.17-0.54), P < 0.0001] had a protective effect.. Combination of insulin glargine and glimepiride may be used during Ramadan in patients with Type 2 diabetes who wish to fast, provided glimepiride is given at the time of breaking the fast and insulin glargine titrated to provide FBG > 6.7 mmol/l.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Islam; Logistic Models; Male; Middle Aged; Prospective Studies; Sulfonylurea Compounds

To evaluate the long-term cost-effectiveness of transferring type 2 diabetes patients to an insulin detemir regimen after failure to achieve adequate control with oral antidiabetic agents (OADs) alone, or in combination with neutral protamine hagedorn (NPH) insulin, or with insulin glargine in Germany.. A computer simulation model of diabetes was used to make long-term projections of future clinical outcomes and direct medical costs based on findings from a German subanalysis of the PREDICTIVE trial. The study analysed the impact of converting patients failing their current treatments to an insulin detemir regimen. Therapy conversion to insulin detemir +/- OADs was associated with a significant reduction in glycosylated haemoglobin (HbA(1)c) compared with OADs alone, NPH insulin +/- OADs, and insulin glargine +/- OADs. Across all three groups, hypoglycaemia rates decreased by 80% and patients lost an average of 0.9 kg of body weight during treatment with insulin detemir +/- OADs.. Therapy conversion to insulin detemir +/- OADs was projected to improve life expectancy by 0.28 years compared with OADs alone, and by 0.13 years compared with the NPH and glargine regimens. Transfer to insulin detemir was associated with improvements in quality-adjusted life expectancy of 0.21 quality-adjusted life years (QALYs) over OADs alone, 0.28 QALYs over NPH +/- OADs, and 0.29 QALYs over glargine +/- OADs. Insulin detemir was associated with savings over patient lifetimes due to reduced diabetes-related complications in all three comparisons.. Therapy conversion to insulin detemir +/- OADs in type 2 diabetes patients failing OADs alone, NPH or insulin glargine regimens was associated with improvements in life expectancy, quality-adjusted life expectancy and cost savings in all three scenarios evaluated.

Topics: Administration, Oral; Body Weight; Costs and Cost Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged; Quality-Adjusted Life Years

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by both insulin resistance and beta-cell failure, resulting in a decline in insulin secretion and increased blood glucose levels. By the time T2DM is clinically diagnosed, only 50% of normal beta-cell function remains, leading to altered control of fasting and/or postprandial glucose. The aim of this review is to summarize the options for introduction of basal insulin, in particular insulin glargine, and the advantages and disadvantages of using insulin glargine vs. alternative insulins or vs. oral agents. Overall, the studies included in this review show that insulin glargine is associated with a lower risk of hypoglycaemia vs. both neutral protamine Hagedorn insulin and premixed insulin formulations, alongside clinically important improvements in glycaemic control. Furthermore, insulin glargine is associated with greater improvements in glycaemic control vs. intensification of oral therapy. Thus, insulin glargine should be a preferred option when starting insulin therapy for people with T2DM.

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Synergism; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Sulfonylurea Compounds

Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Iowa Care (Iowa Medicaid), USA, switched insulin glargine to insulin detemir in subjects with diabetes mellitus without the approval of healthcare providers. This study set out to examine the impact of transition on parameters of diabetes management in type 1 diabetes.. This was a retrospective review of the records of subjects with type 1 diabetes up to August 2007 in whom transition occurred. Subjects completing 6 months of insulin detemir therapy were included. Twenty-four subjects switching from insulin glargine to insuline detemir (group 1) fulfilled the duration with insulin detemir. Glycaemic control (glycosylated haemoglobin [HbA1c]), bodyweight, daily insulin dose (units), total and insulin glargine or insulin detemir and rapid-acting insulin aspart and hypoglycaemic events during the last 4 weeks, pre-switch and again at 6 months post-switch were assessed. Records of 21 age-matched subjects and continuing insulin glargine for 6 months (group 2) were examined. Subjects switched from insulin glargine to insulin detemir in the same daily dose. The daily doses of insulin detemir and aspart in group 1 were adjusted by telephone weekly based on blood glucose monitoring until stabilization occurred. Subjects were followed up in the outpatient clinic every 3 months.. Subjects in group 1 changed to insulin detemir twice a day because of a significant rise in hypoglycaemia with the daily dose used once a day. Glycaemic control remained stable on continuing insulin glargine; HbA1c 7.6+/-0.3 to 7.8+/-0.3%, while it worsened on switching to insulin detemir; HbA1c 7.9+/-0.6 to 8.8+/-0.8 despite a higher daily dose; insulin detemir 46+/-9 U/day versus pre-switch insulin glargine 36+/-8 U/day and group 2 insulin glargine 35+/-6 U/day; and greater total insulin dose: 80+/-12 U/day versus 68+/-10 pre-switch and group 2 insulin glargine 62+/-10 U/day (p<0.05 for all comparisons). Bodyweight and hypoglycaemic events were not significantly different pre- and post-switch.. Switching to insulin detemir from glargine is likely to result in lapse of glycaemic control despite a higher daily insulin dose, increased number of injections and need for frequent evaluations.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Iowa; Male; Medicaid; Retrospective Studies; Therapeutic Equivalency; Time Factors; Treatment Outcome; United States

The aim of this study was to evaluate the safety and efficacy of insulin detemir in type 2 diabetes patients previously receiving NPH insulin (NPH group, n = 175) or insulin glargine (glargine group, n = 118) in combination with oral antidiabetic drugs (OADs).. Patients were transferred to insulin detemir, while the OAD regimen and number of injections remained the same. The incidence of serious adverse drug reactions, including major hypoglycaemia, and haemoglobin A(1c) (HbA(1c)), fasting glucose, within-patient fasting glucose variability and body weight change were measured at 14 weeks.. Glycaemic control improved in both NPH (HbA(1c) = -0.2%, p < 0.05; fasting glucose -1.0 mmol/l, p < 0.0001) and glargine (HbA(1c) = -0.6%, p < 0.0001; fasting glucose -1.4 mmol/l, p < 0.0001) groups, including a reduction in fasting glucose variability (p < 0.01 for both). The incidence of total and nocturnal hypoglycaemia was reduced in both NPH and glargine groups. The incidence of major hypoglycaemia was low and did not change significantly during the follow-up period. Mean body weight was significantly reduced in the NPH (-0.7 kg, p < 0.01) and glargine (-0.5 kg, p < 0.05) groups.. These results indicate that in type 2 diabetes, transferring from other basal insulins to insulin detemir in combination with OADs was associated with improvements in glycaemic control, which were accompanied by a reduced risk of hypoglycaemia and a reduction in body weight.

Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

Hypoglycemia is a common consequence of achieving tight glycemic control for patients with type 2 diabetes, with clinical effects ranging from occasional mild discomfort to incapacitation, coma, or in rare cases, death. Severe hypoglycemic events, particularly those resulting in emergency medical intervention or hospitalization, incur substantial medical costs for patients and the healthcare system. Although vigilance is needed for the possibility of severe events, hypoglycemia need not be a barrier to effective glycemic control in type 2 diabetes. Data from clinical trials and meta-analyses have demonstrated that the basal insulin analog insulin glargine results in a reduced rate of severe hypoglycemic events compared with conventional insulin therapy such as neutral protamine Hagedorn (NPH) insulin. Overall, use of insulin glargine compared with NPH insulin appears to reduce the risk of nocturnal and severe hypoglycemia by 40% to 60% and may result in cost savings. Analyses of hypoglycemia rates from "real-world" clinical practice databases and retrospective analyses of medical claims data also have revealed reduced rates with insulin glargine, consistent with the findings from clinical trials.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insurance Claim Review; Medical Records Systems, Computerized; Meta-Analysis as Topic; Randomized Controlled Trials as Topic

To examine pregnancy outcome in women with Type 1 diabetes treated with glargine.. Glargine use in pregnancy was surveyed over 2 years in 20 UK obstetric-diabetes centres. Outcomes, including maternal complications, miscarriage, congenital abnormalities, perinatal morbidity and mortality, were recorded in a standardized format.. Outcomes on 109 babies from 115 women with Type 1 diabetes were collected. Insulin glargine was used prior to pregnancy in 69% of women, started during pregnancy in 30%, and stopped at booking in one patient. Insulin aspart was the bolus insulin in 45%, lispro in 42% and human soluble in 8% of women. HbA(1c) fell from 8.1 +/- 0.2% at booking to 6.8 +/- 0.1% during the third trimester. Background retinopathy developed in one patient, worsened in seven and laser photocoagulation was required in three women. Preeclampsia occurred in 12%, and 14% of women had more than one episode of severe hypoglycaemia. One hundred and nine babies were live born, with six miscarriages and no neonatal deaths. The mean gestational age was 37.5 weeks, and mean birth weight was 3500 g. Three babies had congenital abnormalities (malformation rate = 28/1000). Neonatal hypoglycaemia was seen in 46% and hyperbilirubinaemia in 22% of babies. No major adverse outcome was noted in a smaller subset of five Type 2 and seven gestational diabetes patients on glargine.. The use of glargine in Type 1 diabetes during pregnancy was not associated with any unexpected adverse maternal or fetal outcome in this study.

Topics: Abortion, Spontaneous; Adult; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Prospective Studies

Insulin glargine is a long-acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes.. We evaluated the clinical course of diabetes in children and adolescents who were switched from NPH to insulin glargine.. Between August 2003 and November 2004, a total of 76 subjects were switched to glargine in our clinic, treating 340 children with type 1 diabetes. All the subjects had been receiving insulin NPH, and their serum C-peptide levels had been non-detectable for at least 1 yr. Data were collected retrospectively, and 12-18 months after the change, experiences with glargine were inquired using a questionnaire. Seven subjects (9.2%) discontinued glargine before 12 months, and seven refused to participate.. Data for 62 subjects were analyzed. At the switch (0 months), their mean age was 12.7 yr (range 5.1-17.5), mean duration of diabetes was 6.7 yr (range 1.8-14.3), and mean hemoglobin A1c was (HbA1c) 9.2%. Twelve months later (+12 months), the mean HbA1c remained similar (9.2%), the proportion of long-acting insulin was smaller (47.7 vs. 58.1%; p < 0.001), and the daily insulin dose was lower (0.97 vs. 1.05 IU/kg; p < 0.001). The number of injections was lower at +12 months (17.7% with more than five injections vs. 64.5%; p < 0.001). No differences were seen in weight for height or the number of severe hypoglycemias. Most subjects who continued with glargine for > or =12 months considered glargine better than NPH.. A switch to insulin glargine retains a similar glycemic control and does not change the number of severe hypoglycemias.

Topics: Adolescent; Age of Onset; Biomarkers; Blood Glucose; Body Height; Body Weight; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Reference Values; Retrospective Studies

Topics: Blood Glucose Self-Monitoring; Diabetes Mellitus; Drug Overdose; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Self Administration

Glargine improves glucose control and reduces the risk of nocturnal hypoglycemia compared with neutral protamine Hagedorn (NPH) insulin. To date, only one study has measured the effects of glargine on health-related quality of life (HRQL); the aim of this study was therefore to confirm the beneficial effects of glargine on disease-specific HRQL in type 1 diabetes.. Forty-seven patients (mean age, 46 range, 25-74; males, 54%) with diabetes of at least 1-year duration, and with suboptimal glucose control under intensive insulin treatment (IIT), were switched from NPH to glargine. Forty patients maintained on IIT were used as controls. Diabetes-related HRQL was assessed using the Well-being Enquiry for Diabetics (WED), before and after a 6- to 8-month switch to glargine. An 11-item questionnaire based upon diabetes-specific issues was used to assess treatment satisfaction and perceived changes after switching. On glargine, the mean glycosylated hemoglobin decreased by 0.7% (treatment vs. baseline, P<0.0001) and several WED scores improved (discomfort, P=0.020; impact, P=0.0002; total score, P=0.0005). WED changes were associated with a lower perceived risk of hypoglycemia and less problems in daily life on glargine.. The results of this study show that the beneficial effect of glargine is not limited to better metabolic control; the burden of type 1 diabetes mellitus on everyday life is also reduced.

Topics: Adult; Aged; Cost of Illness; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Topics: Diabetes Mellitus, Type 1; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation (PREDICTIVE) Study is a large, multi-centre, observational study assessing the safety and efficacy of insulin detemir in everyday clinical practice.. This subgroup analysis of the German cohort of PREDICTIVE evaluates over 3 months, patients with type 2 diabetes who were transferred to insulin detemir +/- oral antidiabetic drugs (OADs) from an OAD-only regimen (n = 1321), NPH insulin +/- OADs (n = 251) or insulin glargine +/- OADs (n = 260).. Among all groups, 3 months after starting treatment with insulin detemir, total, daytime and nocturnal hypoglycaemic events/patient were reduced by 84, 80 and 90%, respectively, from baseline. No major hypoglycaemic events were reported during treatment with insulin detemir. HbAlc was significantly reduced from baseline in each of the subgroups (-1.29,-0.60 and-0.59% for patients previously taking OADs only, NPH insulin +/- OADs and insulin glargine +/- OADs respectively; p < 0.0001), as was fasting blood glucose (FBG) (-58.1,-29.1 and-24.6 mg/dl; p < 0.0001) and FBG variability-8.2 mg/dl,-5.7 mg/dl; p < 0.0001 and -5.1 mg/dl; p = 0.0008). All subgroups combined lost an average of 0.9 kg of body weight (p < 0.0001) during the study. Total daily basal insulin dose increased slightly from baseline for those patients on a prior insulin regimen, and in this study 79% of patients used insulin detemir once daily.. These data confirm the short-term safety and efficacy of insulin detemir +/- OADs in a real-world scenario and support the findings of randomized controlled clinical trials with insulin detemir, including its limited effects on body weight.

Topics: Administration, Oral; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Loss

To evaluate the changes in the glycemic profile and metabolic control after introducing glargine in children with DMT1 in a one-year follow up.. 70 children (36 boys) at the average age of 12.03+/-2.50 with the mean diabetes duration of 3.35+/-2.19 years were observed. Glargine was substituted for NPH in children treated with multiple daily injections.. The analysis showed the differences in the dynamics of changes in mean glycemia based on home blood glucose monitoring and HbA1c between prepubertal children (Group 1) and teenagers (Group 2). A significant reduction in mean glycemia from baseline to 12 months was observed at all chosen points in Group 2: fasting glycemia (125+/-27 mg/dl vs 117+/-17 mg/dl,p<0.05), bedtime glycemia (128+/-24 mg/dl vs. 117+/-20 mg/dl,p=0.001) and 3 a.m. glycemia (143+/-47 mg/dl vs. 90+/-25 mg/dl,p<0.001). A significant decrease in mean glycemia in Group 1 was observed from the beginning of treatment only at bedtime (0-12 months:129+/-27 mg/dl vs. 112+/-25 mg/dl,p=0.001) and at 3 am with the delay (6-12 months:122+/-36 mg/dl vs. 90+/-22 mg/dl,p<0.05). A significant improvement in HbA1c between baseline and 12 months was observed in both groups but with different dynamics of changes: 6.91+/-0.77% vs. 6.59+/-0.65% (p<0.05) and 7.44+/-1.26% vs. 7.18+/-1.58% (p=0.001) respectively in the groups. A trend towards decreasing the number of hypoglycemic episodes and no changes in BMI and insulin requirement were noted.. Introduction of glargine provides diabetic children with a better stabilization of the daily glycemic profile even in the cases of baseline good metabolic control. The rate of reaching the target in a long-term observation depends on age. A slower reduction of glycemia observed in smaller subjects suggests a great individuality in the regimen of diabetic children.

Topics: Adolescent; Blood Glucose; Body Mass Index; Child; Child, Preschool; Diabetes Mellitus, Type 1; Fasting; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Puberty

Topics: C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Secreting Cells; Insulin, Long-Acting; Metformin; Peptides; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Venoms; Weight Gain; Weight Loss

We present a case of rapid onset of glycogen storage hepatomegaly, caused by a massive dose of long-acting insulin and large doses of glucose, in a type-2 diabetic patient. A 41-year-old man was admitted to our hospital because of hypoglycemia and unconsciousness following subcutaneous administration of 180 units of insulin glargine in a suicide attempt. Despite continuous hypercaloric infusion with additional intravenous glucose injections, hypoglycemia persisted for 36 hours. Although the hepatic function was normal and no hepatomegaly was detected on admission, the liver function tests became abnormal and hepatomegaly was detected on hospitalization day 3. Plain abdominal computed tomography (CT) scanning confirmed liver enlargement, with hepatic CT attenuation markedly elevated at 83.7 HU. Liver biopsy revealed hepatocytic glycogen deposition with edematous degeneration. Based on these findings, the diagnosis was made as rapid onset glycogen storage hepatomegaly caused by administration of a massive dose of long-acting insulin and supplementation with large doses of glucose. With improved glycemic control, the liver function improved, the CT findings of hepatomegaly improved, and the hepatic CT attenuation decreased. Repeat liver biopsy also confirmed almost complete disappearance of glycogen deposits. When hepatic dysfunction or hepatomegaly is detected during treatment with insulin, the possibility of hepatic glycogen deposition should be considered. CT scanning and liver biopsy were useful in diagnosing this case.

Topics: Adult; Diabetes Mellitus, Type 2; Diabetic Coma; Glucose; Hepatomegaly; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Liver; Liver Glycogen; Male; Suicide, Attempted

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

Rates of hypoglycemic events and their associated costs were compared among patients with type 2 diabetes mellitus newly initiated on insulin glargine or a premixed insulin fixed-combination product.. Patients newly initiated on insulin glargine or premixed insulin fixed-combination products (including pen delivery systems) between June 1, 2001, and February 29, 2004, were identified using an administrative claims database. Hypoglycemic events were identified from International Classification of Diseases, 9th Revision, Clinical Modification codes. Multivariate analyses were performed.. A total of 2315 patients met the inclusion criteria. Of those, 1212 received insulin glargine and 1103 received a premixed fixed-combination insulin product. The mean +/- S.D. treatment duration was 13.7 +/- 8.1 months. Patients treated with premixed insulin had a higher hypoglycemic event rate than glargine patients (13.8 versus 7.0/100 patients/year; p = 0.027), which yielded a number needed to treat of 15 patients. The mean cost per hypoglycemic event was $1049 (95% confidence interval, $426-1672). The mean annual cost of all insulin use was $46 more for the insulin glargine cohort than for those who received premixed insulin ($534 versus $488, respectively) (p < 0.05). Mean postindex insulin use was higher in patients receiving premixed insulin than in those treated with insulin glargine (48.1 versus 43.8 units per day) (p < 0.05).. Patients with type 2 diabetes mellitus who were newly initiated on insulin glargine had a lower rate of hypoglycemic events compared with patients newly initiated on a premixed fixed-combination insulin product. Treatment of 15 patients with insulin glargine instead of premixed insulin for one year would avoid one hypoglycemic event per year.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Insurance Claim Review; Male; Middle Aged; Retrospective Studies

To compare hypoglycemia event rates in patients initiated on long-acting insulin analog (glargine) or intermediate-acting insulin (NPH) and to analyze the associated cost-consequence from a managed care perspective.. A retrospective analysis of pharmacy and medical claims and electronic laboratory result data using a southeastern United States managed care health plan.. Patients newly initiated on glargine or NPH between July 1, 2000 and August 31, 2002 were included. Hypoglycemia events were identified from medical claims by their ICD-9CM codes. Multivariable techniques were used to compare hypoglycemia event rates between cohorts.. A total of 1434 patients were eligible (glargine = 310, NPH = 1124). The mean age was 53 years +/- 17 years and 51% of patients were male. The mean treatment duration was 8.6 months +/- 4.5 months. Multivariate analyses showed that patients in the NPH group had a higher hypoglycemia event rate than the glargine group (18.3 versus 7.3 per 100 patients per year; p = 0.009). The number needed to treat (glargine versus NPH) to avoid one hypoglycemia event per patient per year was nine patients at an A1C of 7%. The mean annual index medication cost was $47 more for glargine ($390) than for NPH ($343) per patient per year (p = 0.042). The mean cost per hypoglycemia event was $1087 (95% CI: $764-$1409).. Patients treated with glargine had significantly lower hypoglycemia event rates compared to the NPH group. The risk difference indicated that one hypoglycemia event would be avoided for every nine patients treated with glargine instead of NPH. The cost increase associated with treating nine patients with glargine rather than NPH is less than the cost of treating one hypoglycemia event. In this population, the savings associated with reduced hypoglycemic events more than offset the increased acquisition cost associated with glargine.

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Health Care Costs; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Insurance Claim Review; Male; Managed Care Programs; Middle Aged; Poisson Distribution; Retrospective Studies; Risk Assessment; Risk Factors; Southeastern United States; Time Factors

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Overdose; Emergency Medicine; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Intravenous; Insulin; Insulin Glargine; Insulin, Long-Acting; Suicide, Attempted

The purpose of this study was to compare the effect of insulin glargine (glargine) and NPH insulin (NPH) on long-term outcomes in type 2 diabetes patients using the Diabetes Mellitus Model (DMM).. The DMM predicts short- and long-term complications over ten years using data in studies published previously. The main effect on outcome is the influence of the treatment on the HbA1c level which is simulated over time. The simulation was based on a cohort size of 10,000 type 2 diabetes patients taking either glargine or NPH. The best scenario, baseline scenario and worst case scenario were simulated based on differences of 0.13%, 0.44% and 0.85%, respectively, in HbA1c values and corresponding to potentially attainable improvements with comparable or lower hypoglycemia rates in glargine-treated patients and NPH-treated patients. Assumptions for scenarios 1, 2 and 3 were based on a regression analysis of clinical trial data (pooled data clinical trials comparing glargine and NPH) in which the effect of glargine on the HbA1c/hypoglycemia incidence ratio was superior to that of NPH.. The relative risks (RR, glargine/NPH) obtained for scenarios 1, 2 and 3 were 0.97, 0.89 and 0.81, respectively, for long-term microvascular complications and 0.99, 0.95 and 0.91, respectively, for long-term macrovascular complications. RR reductions ranged from 1% in the less optimistic scenario to > 20% in the "best case" scenario. Sensitivity analyses showed that variations in the mean baseline HbA1c values and duration of the diabetes were without effect on these outcomes.. Although there is a need to corroborate the results of these simulations with real, long-term clinical data, they have demonstrated that, assuming comparable or lower rates of hypoglycemia, a better glycemic control (HbA1c reduction) can be expected with glargine when compared to NPH together with a reduction in long-term complications, mortality and associated costs.

Topics: Computer Simulation; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sensitivity and Specificity

Children under 6 yr have the highest incidence of severe hypoglycemia (SH) and the greatest likelihood of brain damage from SH. The purpose of this study is to evaluate the use of insulin glargine (Lantus in children under age 6 with type 1 diabetes (T1D).. The electronic medical records were reviewed for patients under age 6 during the first 6 months of insulin glargine therapy and compared with age, sex, and duration of diabetes for matched control patients on neutral protamine Hagedorn (NPH) insulin. Data from 128 subjects (32 male pairs and 32 female pairs) were collected relating to the incidence of severe and non-severe hypoglycemic events, hemoglobin A1c (HbA1c) values, body mass index (BMI), and daily insulin dose. Additionally, parents were asked to complete a diabetes Quality of Life (QoL) survey.. In the 6 months before the study period, the glargine group had 16 SH events compared with three in the 6 months post-glargine. The comparison (NPH) group had seven and six SH events in their respective 6-month periods. Nighttime SH events in the glargine group decreased from 12 prestudy events to one during the study period. The average daily insulin dose in the glargine group was higher than that in the NPH group (0.8+/- 0.2 vs. 0.7+/- 0.2 U/kg/day; p=0.03). The HbA1c values, BMI, and QoL responses were not significantly different between the two groups.. SH was decreased, particularly at night (from 12 episodes to one), after the introduction of glargine in young children with T1D.

Topics: Body Mass Index; Child, Preschool; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Quality of Life

In a prospective study on 11 patients with Type 1 diabetes we evaluated the glycaemic control and hypoglycaemic episodes on a combination therapy of pre-mixed and glargine insulin. Glycosylated hemoglobin (HbA1C), fasting (FPG) and Post Prandial blood glucose (PPG) levels were recorded at baseline and three monthly intervals for a period of 6 months. The mean HbA1C reduced from 9.5 to 7.3 %, incidence of hypoglycemias from 1.6 to 0.8, mean FPG from 146.5 to 90.4 and mean PPG from 258.4 to 184 over a six-month observation period. This regimen also helps to avoid injection of insulin before lunch so that child's school schedule is minimally disturbed and yet the incidence of hypoglycemia is not increased.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies

Insulin glargine is a long-acting insulin analogue with favourable clinical characteristics. We studied a slim 24-year-old female with Type 1 diabetes who repeatedly experienced severe hypoglycaemia after switching from NPH insulin to insulin glargine at identical daily doses.. Clinical examination and high-resolution ultrasound.. The patient frequently placed her injections into muscle tissue, followed by unexpected rapid insulin action. After correction of her injection technique, hypoglycaemia did not recur.. The long-acting kinetics of insulin glargine require precipitation in the subcutaneous tissue. Therefore, each patient's injection technique should be carefully checked when treatment with insulin glargine is initiated, particularly in young and lean individuals.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Intramuscular; Insulin; Insulin Glargine; Insulin, Long-Acting

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Nausea; Peptides; Venoms; Vomiting

Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Postprandial Period; Titrimetry; Treatment Failure

Stringent glycemic control is important for preventing the development or progression of complications in type 1 diabetes. This goal may best be achieved by intensive insulin replacement therapy that closely follows the physiologic patterns of secretion observed in patients without diabetes. Premixed insulin formulations of human regular and NPH insulin are commonly used to control blood glucose levels throughout the day, but because these preparations do not mimic the physiologic profile of insulin release, hypo- and hyperglycemia may ensue. Using human regular insulin to control mealtime hyperglycemia is similarly problematic, and thus recently developed rapid-acting insulin analogues, such as lispro and aspart, are now preferred for prandial glucose control. In addition, regimens that combine insulins--eg, NPH insulin for meeting the demand for round-the-clock basal insulin secretion and a rapid-acting insulin analogue to cover mealtime insulin requirements--improve glycemic control, but increase risk of nocturnal hypoglycemia. The ideal basal insulin replacement should feature a uniform continuous release of insulin with a long duration to minimize hypoglycemia. Although such a profile may be achieved with a continuous subcutaneous insulin infusion, new basal insulin analogues, such as once daily, 24-hour insulin glargine, combined with mealtime lispro or aspart, offer comparable glycemic control without the drawbacks of insulin pump use in type 1 diabetes. Insulin glargine reduces the frequency of nocturnal hypoglycemia compared with NPH when used with rapid-acting analogues and thus facilitates optimal insulin replacement therapy.

Topics: Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Topics: Circadian Rhythm; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

Glargine (Lantus) is a recently approved, long-acting insulin analog that is increasingly being used in children with diabetes. The aim of this retrospective chart review was to summarize our experience in starting glargine in children and adolescents with diabetes. SUBJECTS AND STUDY METHODS: We reviewed the medical records of 71 children with type 1 diabetes (29 boys and 42 girls) who initiated glargine therapy to improve glycemic control between 1 June 2001 and 30 June 2002. Data were collected for 6 months before and 6 months after adding glargine.. Subjects' mean age [+/-standard deviation (SD)] at diagnosis of diabetes was 7.5 +/- 4.1 yr. Mean age at initiation of glargine therapy was 11.5 +/- 4.9 yr. The total daily long-acting insulin dose decreased by about 20% after initiating glargine therapy. There were no significant differences in hemoglobin A1c (HbA1c) and blood glucose control prior to and after initiating glargine therapy (HbA1c at baseline 8.9 +/- 1.6% and HbA1c after 6 months of glargine therapy was 8.9 +/- 1.5%). Overall, blood glucose concentrations did not differ significantly throughout the study. Patients who switched to glargine because of nocturnal hypoglycemia had a 65% decrease in nocturnal blood glucose reading less than 50 mg/dL. There were three seizures in the first week after initiating glargine therapy.. This retrospective study suggests that glargine is at least as effective as other long-acting insulins but that care must be taken during the conversion process to avoid hypoglycemia.

Topics: Adolescent; Blood Glucose; Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Osmolar Concentration; Retrospective Studies; Seizures; Treatment Outcome

Topics: Adolescent; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting

In the last few years short-acting insulin analogs have become increasingly popular. Their introduction has unmasked serious deficiencies in the capacity of isophane insulin to provide a stable basal insulinaemia. The long-acting insulin analogs, insulin glargine and insulin detemir, have been developed as alternatives to isophane insulin. Insulin glargine has a long duration of action and has demonstrated its usefulness in diabetes type 2, specifically a lower incidence of (nocturnal) hypoglycaemia compared to isophane insulin, in clinical practice. Insulin detemir has a very low variability in absorption and also seems to reduce the risk of nocturnal hypoglycaemia in diabetes type 1. More studies are, however, needed. Because of the higher costs of these novel insulins, the decision to switch a patient from isophane insulin to an insulin analog has to be made on an individual basis.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Controlling blood glucose levels in patients with diabetes often requires aggressive treatment, which may in turn cause hypoglycemia and/or decreased health-related quality of life (HRQOL). Insulin glargine, a long-acting insulin, has shown benefits of decreased nocturnal hypoglycemia without significant weight gain, while providing good glycemic control in clinical trials. These benefits have often been reported in studies of less than 1 year duration. The objective of this study was to evaluate the effectiveness of insulin glargine over a 12-month period in a clinical practice setting, and measure its effects on HRQOL in a subset of patients.. Patients with diabetes in a large private endocrinology practice were initiated on insulin glargine. Patients were divided into 2 cohorts: the first group included patients with type 1 diabetes (T1D, n = 135); the second group included patients with type 2 diabetes previously on insulin and/or oral agents (T2D, n = 180). The HRQOL subset analysis included 50 patients from the above study. Patients completed a 40-item questionnaire adapted from the Diabetes Symptom Checklist-Revised (DSC-R) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at weeks 0, 2, 6, 12, and 16.. Patients in both cohorts experienced statistically significant decreases in mean ( +/- SD) A1C: group T1D, -0.28 +/- 1.47 (P = 0.0307); group T2D, -0.60 +/- 1.51 (P < 0.0001), with no significant changes in body mass index. In the year following insulin glargine therapy, there were significantly fewer hypoglycemic events per patient than in the year prior to insulin glargine therapy (group T1D: -0.33, P = 0.002; group T2D: -0.20, P = 0.004). HRQOL subset analysis also revealed a significant decrease in A1C (P < 0.0001) after 16 weeks of therapy with insulin glargine. In this subset of patients, there was a significant improvement in overall well being (P = 0.0019), emotional well being (P = 0.003), total symptom scores (P < 0.0001), and total symptom distress (P < 0.0001). The limitations of the study are those inherently associated with naturalistic observational studies such as recall bias and compliance.. Insulin glargine use over a 12-month period in a clinical practice setting was shown to significantly improve A1C without adversely impacting weight or the occurrence of hypoglycemia. Significant improvements were also observed in HRQOL.

Topics: Administration, Oral; Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Our ability to gain strict glycemic control in diabetes has improved with the introduction of novel insulins. New formulations, novel insulin molecules, and various methods of insulin delivery are able to more closely approximate the normal physiologic insulin response than conventional preparations. In this article, the authors review the development of insulin formulations and the pharmacology of currently available insulin molecules and those soon to be on the market.

Topics: Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Time Factors

To determine the effect of insulin glargine on glycemic control in pediatric type 1 and 2 diabetes, a retrospective repeated-measure analysis of variance was performed of hemoglobin A1C (HbA1C), frequency of hypoglycemia and hyperglycemia, mean blood glucose, body mass index (BMI), and daily weight-adjusted insulin dosage before and after institution of glargine therapy in 72 children and adolescents with diabetes. At glargine start, age range was 1.2-19.6 years, mean age was 12.5 +/- 4.6 years, BMI was 22.48 +/- 6.3 kg/m(2), and mean HbA1C was 9.7 +/- 1.9%. Mean duration of diabetes was 3.58 years, and mean baseline insulin dose was 0.93 U/kg/day. Gender breakdown was 60% female, and the majority (83%) had type 1 diabetes. Average HbA1C decreased from 9.5% pre-glargine to 8.6% post-glargine (p < 0.001). HbA1C decrease was significant in both types of diabetes without a concomitant increase in frequency of hypoglycemia, BMI, or weight-adjusted insulin dose. Hypoglycemia decreased significantly in type 1 diabetes. Thus, glargine therapy may decrease HbA1C and frequency of hypoglycemia in toddlers, children, and adolescents with diabetes, without an increase in BMI or insulin requirements.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Patient Compliance; Retrospective Studies; Sex Factors; Time Factors

Topics: Administration, Oral; Adult; Age Factors; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Time Factors

Topics: Adolescent; Blood Glucose; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Weight Gain

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Prospective Studies; Randomized Controlled Trials as Topic; Therapeutic Equivalency

Insulin glargine is an extended-action biosynthetic human insulin. It precipitates in the neutral environment of subcutaneous tissue and is thus gradually absorbed into the bloodstream. The addition of small amounts of zinc to the formulation further delays absorption. In small euglycaemic clamp studies, the onset of action of insulin glargine was shown to be later, the duration of action longer and the time-action profile flatter than that of Neutral Protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus and healthy volunteers. Four large clinical trials of up to 28 weeks' duration have shown that a single bedtime dose of insulin glargine, in combination with preprandial short-acting insulin, is as effective or more effective than once or twice daily NPH plus short-acting insulin in improving glycaemic control in patients with type 1 diabetes mellitus. In 3 large comparative trials, insulin glargine decreased glycosylated haemoglobin and/or fasting blood glucose levels to a similar extent to that seen with NPH insulin in patients with insulin-dependent or non-insulin-dependent type 2 diabetes mellitus, either as monotherapy or in combination with oral hypoglycaemic agents. Insulin glargine appears to be well tolerated. A lower incidence of hypoglycaemia, especially at night, was reported in most trials with insulin glargine when compared with NPH insulin.

Topics: Blood Glucose; Circadian Rhythm; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Glycated Hemoglobin; Half-Life; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Recombinant Proteins