insulin-glargine and Body-Weight

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

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

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

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

Elderly patients with type 2 diabetes mellitus (T2DM) present therapeutic challenges related to co-morbidities, treatment adherence, and safety. This study examines the efficacy and safety of insulin glargine compared to other glucose-lowering interventions in younger and older adults.. In this pooled analysis of 24-week data from nine prospective open-label, multicenter, phase 3/4, two-arm, parallel-group, randomized controlled trials, patients with T2DM aged 18-80 years received insulin glargine (used as a basal insulin regimen) or comparators (including rosiglitazone, pioglitazone, insulin lispro, insulin lispro 75/25, NPH insulin, NPH insulin 30/70, and lifestyle/dietary measures). Endpoints included change from baseline to week 24 in: glycated hemoglobin; fasting plasma glucose; body weight; body mass index; insulin dose; incidence of nocturnal, daytime, or any hypoglycemia. Results were stratified by age (<65, ≥65, 65-74, and ≥75 years) and treatment (insulin glargine or comparator).. A total of 2,938 patients were included (2,263 aged <65 years, 675 aged ≥65 years). Similar levels of glycemic control were achieved in both younger (<65 years) and older (≥65 years) patients with T2DM. Insulin glargine was associated with better glycemic control and a reduced incidence of daytime and any hypoglycemia versus comparator interventions in both younger and older T2DM patients.. This analysis suggests that insulin glargine may represent a safe option to improve glycemic control in older patients with T2DM.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Body Weight; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Insulin have been recommended to decrease glycosylated hemoglobin (HbA1c) level in type 2 diabetes mellitus (T2DM) patients whose blood glucose control are unsatisfactory by using oral hypoglycemic drugs.. To systematically estimate the therapeutic effect and security of insulin glargine and insulin detemir for treatment of type 2 diabetes mellitus.. We searched the Cochrane library, PubMed, EMBASE, etc databases. Quality evaluation of all randomized control tests (RCT) enrolled was conducted according to Cochrane manual, and meta-analysis was performed by using RevMan5.0 software.. Both insulin glargine and insulin detemir can effectively control T2DM patient's blood glucose.. Insulin detemir has evident superiority on reducing body weight than insulin glargine. As the doses are concerned, daily insulin dose of insulin detemir is higher than insulin glargine.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

In May 2008, the National Institute for Health and Clinical Excellence (NICE) issued an updated guideline [clinical guideline (CG) 66] for the management of all aspects of type 2 diabetes. This report aims to provide information on new drug developments to support a 'new drugs update' to the 2008 guideline.. To review the newer agents available for blood glucose control in type 2 diabetes from four classes: the glucagon-like peptide-1 (GLP-1) analogue exenatide; dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin and vildagliptin; the long-acting insulin analogues, glargine and detemir; and to review concerns about the safety of the thiazolidinediones.. The following databases were searched: MEDLINE (1990-April 2008), EMBASE (1990-April 2008), the Cochrane Library (all sections) Issue 2, 2008, and the Science Citation Index and ISI Proceedings (2000-April 2008). The websites of the American Diabetes Association, the European Association for the Study of Diabetes, the US Food and Drug Administration, the European Medicines Evaluation Agency and the Medicines and Healthcare Products Regulatory Agency were searched, as were manufacturers' websites.. Data extraction was carried out by one person, and checked by a second. Studies were assessed for quality using standard methods for reviews of trials. Meta-analyses were carried out using the Cochrane Review Manager (RevMan) software. Inclusion and exclusion criteria were based on current standard clinical practice in the UK, as outlined in NICE CG 66. The outcomes for the GLP-1 analogues, DPP-4 inhibitors and the long-acting insulin analogues were: glycaemic control, reflected by glycated haemoglobin (HbA1c) level, hypoglycaemic episodes, changes in weight, adverse events, quality of life and costs. Modelling of the cost-effectiveness of the various regimes used the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model.. Exenatide improved glycaemic control by around 1%, and had the added benefit of weight loss. The gliptins were effective in improving glycaemic control, reducing HbA1c level by about 0.8%. Glargine and detemir were equivalent to Neutral Protamine Hagedorn (NPH) (and to each other) in terms of glycaemic control but had modest advantages in terms of hypoglycaemia, especially nocturnal. Detemir, used only once daily, appeared to cause slightly less weight gain than glargine. The glitazones appeared to have similar effectiveness in controlling hyperglycaemia. Both can cause heart failure and fractures, but rosiglitazone appears to slightly increase the risk of cardiovascular events whereas pioglitazone reduces it. Eight trials examined the benefits of adding pioglitazone to an insulin regimen; in our meta-analysis, the mean reduction in HbA1c level was 0.54% [95% confidence interval (CI) -0.70 to -0.38] and hypoglycaemia was marginally more frequent in the pioglitazone arms [relative risk (RR) 1.27, 95% CI 0.99 to 1.63]. In most studies, those on pioglitazone gained more weight than those who were not. In terms of annual drug acquisition costs among the non-insulin regimes for a representative patient with a body mass index of around 30 kg/m2, the gliptins were the cheapest of the new drugs, with costs of between 386 pounds and 460 pounds. The glitazone costs were similar, with total annual costs for pioglitazone and for rosiglitazone of around 437 pounds and 482 pounds, respectively. Exenatide was more expensive, with an annual cost of around 830 pounds. Regimens containing insulin fell between the gliptins and exenatide in terms of their direct costs, with a NPH-based regimen having an annual cost of around 468 pounds for the representative patient, whereas the glargine and detemir regimens were more expensive, at around 634 pounds and 716 pounds, respectively. Comparisons of sitagliptin and rosiglitazone, and of vidagliptin and pioglitazone slowed clinical equivalence in terms of quality-adjusted life-years (QALYs), but the gliptins were marginally less costly. Exenatide, when compared with glargine, appeared to be cost-effective. Comparing glargine with NPH showed an additional anticipated cost of around 1800 pounds. Within the comparison of detemir and NPH, the overall treatment costs for detemir were slightly higher, at between 2700 pounds and 2600 pounds.. The UKPDS Outcomes Model does not directly address aspects of the treatments under consideration, for example the direct utility effects from weight loss or weight gain, severe hypoglycaemic events and the fear of severe hypoglycaemic events. Also, small differences in QALYs among the drugs lead to fluctuations in incremental cost-effectiveness ratios.. Exenatide, the gliptins and detemir were all clinically effective. The long-acting insulin analogues glargine and detemir appeared to have only slight clinical advantages over NPH, but had much higher costs and did not appear to be cost-effective as first-line insulins for type 2 diabetes. Neither did exenatide appear to be cost-effective compared with NPH but, when used as third drug after failure of dual oral combination therapy, exenatide appeared cost-effective relative to glargine in this analysis. The gliptins are similar to the glitazones in glycaemic control and costs, and appeared to have fewer long-term side effects. Therefore, it appears, as supported by recent NICE guidelines, that NPH should be the preferred first-line insulin for the treatment of type 2 diabetes. More economic analysis is required to establish when it becomes cost-effective to switch from NPH to a long-acting analogue. Also, long-term follow-up studies of exenatide and the gliptins, and data on combined insulin and exenatide treatment, would be useful.

Topics: Adamantane; Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Nitriles; Peptides; Pyrazines; Pyrrolidines; Quality of Life; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; State Medicine; Thiazolidinediones; Triazoles; United Kingdom; Venoms; Vildagliptin

A pooled analysis of randomized controlled trials of individuals with type 2 diabetes mellitus (T2DM) was conducted to compare dosing and impact of two basal insulin analogs, insulin glargine (glargine) and insulin detemir (detemir), on weight and hemoglobin A1c (A1c).. Twenty-two studies of at least 20 weeks in duration in individuals with T2DM initiating glargine/detemir were included. Results were combined using a weighted-average method and a bivariate random effect model. Outcomes included changes in weight, A1c, and insulin dose from study start to end.. One study was head-to-head comparison of glargine and detemir. Detemir (four studies) was administered once or twice daily, with 50% starting on detemir once daily but needing therapy intensification. Glargine was used once daily in all 22 studies. The Egger test was borderline significant for change in weight over the course of the treatment for glargine (0.29; 90% confidence interval [CI] -0.01, 0.58), and heterogeneity was not observed for detemir (-0.18; 90% CI -0.59, 0.23). Heterogeneity was observed for change in A1c over the course of the treatment (glargine, -1.19, 90% CI -1.74, -0.63; detemir, -2.65, 90% CI -4.86, -0.45). Nonheterogeneity for change in A1c over the course of the treatment was achieved by excluding five studies for glargine and one study for detemir; however, all studies were included in subsequent analyses. In the unadjusted model, glargine and detemir showed similar results for mean A1c change (-1.4% vs. -1.4%), weight gain (2.5 vs. 1.7 kg), and weight/A1c (1.8 vs. 1.2 kg/%). A significantly higher detemir dose was needed to achieve the same A1c change (51.5 vs. 38.8 U/day).. Although absolute weight gain was higher with glargine versus detemir, weight gain per A1c change was similar. A higher detemir dose was required to achieve a similar A1c reduction.

Topics: Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

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

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

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

Multiple studies support the efficacy of combining a glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in people with type 2 diabetes inadequately controlled on dual/triple oral therapy. Fixed-ratio combinations of basal insulin + GLP-1RA represent a further advance to facilitate management. We assessed the impact of fixed-ratio combination basal insulin + GLP-1RA treatment on β-cell function.. We analysed data from 351 participants in the LixiLan-G trial (NCT02787551) randomized to receive iGlarLixi (insulin glargine 100 U/ml + lixisenatide) or to continue daily/weekly GLP-1RA, both on top of metformin. Participants received a 2-h meal tolerance test before randomization and at study end (26 weeks), with timed plasma glucose and C-peptide determinations. β-cell function parameters were resolved using mathematical modelling.. In the GLP-1RA group (n = 162), both body weight and glycated haemoglobin decreased at week 26, yet none of the insulin secretion/β-cell function parameters changed significantly. In contrast, in the iGlarLixi group (n = 189), glycated haemoglobin decreased significantly more than in the GLP-1RA group (p < .0001) despite an increase in body weight (+1.7 ± 3.9 kg, p < .0001). Fasting and stimulated insulin secretion decreased at Week 26 (both p < .0001 vs. GLP-1RA), while β-cell glucose sensitivity increased by a median 35% (p = .0032 vs. GLP-1RA). The incremental meal tolerance test glucose area showed a larger reduction with iGlarLixi versus GLP-1RA (p < .0001).. In people with type 2 diabetes on metformin, 26-week treatment with iGlarLixi resulted in a marked improvement in β-cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Metformin; Peptides

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

For the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin-fragment-crystallizable (Fc) has an ultra-long plasma half-life because it recycles through cells, protected from proteolysis.. Glycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS-218d) administered subcutaneously once-weekly.. Five client-owned dogs with naturally occurring DM.. Prospective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate-acting insulin q12h were transitioned to once-weekly injections of a preliminary construct identified as AKS-218d. The dose of AKS-218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS-218d) and during the last week of treatment. Data were compared using nonparametric paired tests.. Once-weekly AKS-218d, compared to baseline twice-daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [-0.5-1.1]; P = .6), fructosamine concentration (-75 mmol/L [-215 to +126]; P = .4), or mean IG (+81 mg/dL [-282 to +144]; P = .8). No adverse reactions were reported.. Control of clinical signs, body weight, and maintenance of glycemia was achieved with this once-weekly novel insulin construct in 4 of 5 dogs.

Topics: Animals; Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Fructosamine; Hospitals, Animal; Hospitals, Teaching; Hypoglycemic Agents; Insulin; Insulin Glargine; Prospective Studies

Variations in the prevalence and etiology of type 2 diabetes (T2D) across race and ethnicity may affect treatment responses. Semaglutide is a glucagon-like peptide-1 analog approved for once-weekly, subcutaneous treatment of T2D.. To compare semaglutide efficacy and safety in race and ethnicity subgroups across the SUSTAIN trials.. Post hoc analysis of data from phase 3 randomized SUSTAIN 1-5 and 7 (pooled), and SUSTAIN 6 trials.. 3074 subjects (SUSTAIN 1-5 and 7) and 1648 subjects (SUSTAIN 6).. Semaglutide 0.5 or 1.0 mg, placebo, or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine 100IU/ml and dulaglutide 0.75 or 1.5 mg).. Change in hemoglobin A1C (HbA1c) and body weight from baseline to weeks 30, 40 and 104, and other efficacy and safety endpoints.. HbA1c was reduced from baseline by 1.0 to 1.5 percentage points and 1.3 to 2.0 percentage points, and body weight was reduced by 2.3 to 4.7 kg and 3.6 to 6.1 kg with semaglutide 0.5 and 1.0 mg, respectively, across race and ethnicity subgroups. Minor changes in blood pressure and lipid profiles were observed. Adverse events (AEs) were reported in similar proportions of subjects across trials. More Asian versus other race subgroups discontinued treatment prematurely due to AEs. The most commonly reported AEs were gastrointestinal disorders.. In this SUSTAIN trials post hoc analysis, semaglutide was associated with consistent and clinically relevant reductions in HbA1c and body weight in subjects with T2D, with minor variations in efficacy and safety outcomes associated with race or ethnicity.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Ethnicity; Female; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin Glargine; Male; Middle Aged; Racial Groups; Recombinant Fusion Proteins; Treatment Outcome

Efficacy and safety of dapagliflozin plus saxagliptin (DAPA + SAXA) were compared with insulin glargine (INS) in patients with type 2 diabetes (T2D) in a 52-week extension study.. This international Phase 3 study randomized adults with T2D on metformin with/without sulphonylurea. They received DAPA + SAXA or INS for 24 weeks (short-term) with a 28-week (long-term) extension. Week 52 exploratory endpoints included adjusted mean change from baseline in glycated haemoglobin A. Of the 1163 patients enrolled, 643 received treatment; 600 (DAPA + SAXA, 306; INS, 294) entered the long-term phase. At 52 weeks, HbA1c [adjusted least squares (LS) mean; 95% confidence interval (CI)] decreased more with DAPA + SAXA (-1.5% [-1.6%, -1.4%]) than with INS (-1.3% [-1.4%, -1.1%]); the LS mean difference (95% CI) was -0.25% (-0.4%, -0.1%; P = 0.009). Total body weight reduced with DAPA + SAXA [LS mean (95% CI): -1.8 kg (-2.4, -1.3)] and increased with INS [LS mean (95% CI): +2.8 kg (2.2, 3.3)]. More patients on DAPA + SAXA (17.6%) achieved HbA1c <7.0% without hypoglycaemia versus those on INS (9.1%). Rescue medication was required by 77 patients (23.8%) and 97 patients (30.4%) in the DAPA + SAXA and INS groups, respectively.. DAPA + SAXA treatment was non-inferior to INS in reducing HbA1c and body weight, and in achieving optimal glycaemic control without hypoglycaemia in patients with T2D 52 weeks after initiation.

Topics: Adamantane; Adult; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Treatment Outcome

Type 2 diabetes mellitus is closely related to nonalcoholic fatty liver disease(NAFLD). More and more attention has been paid to the efficacy of liraglutide in the treatment of NAFLD, but the clinical evidence is still insufficient.. The purpose of this study was to use proton magnetic resonance spectroscopy (H-MRS) assessment of metformin alone poor blood glucose control of obese patients type 2 diabetes with NAFLD, added with insulin glargine, liraglutide or placebo effect in improving the fatty liver.. This is a 26-week, single-center, prospective, randomized placebo-controlled study. From September 2016 to July 2018, 128 patients with type 2 diabetes and NAFLD were enrolled in the China joint logistics team 900 hospital. The primary endpoints were the changes in intrahepatic content of lipid (IHCL), abdominal adiposity [subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)], from baseline to week 26 (end of treatment) and the changes in liraglutide group or insulin glargine group versus change in placebo group. Secondary endpoints included the changes in liver function (AST and ALT), glycemia (HbA1c and FPG), body weight, and BMI.. A total of 96 patients with type 2 diabetes and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on insulin glargine, liraglutide, or placebo. After 26 weeks of treatment, compared to the placebo group, in the liraglutide and insulin glargine groups, IHCL significantly decreased from baseline to week 26 (liraglutide 26.4% ± 3.2% to 20.6% ± 3.9%, P < 0.05; insulin glargine 25.0% ± 4.3% to 22.6% ± 5.8%, P > 0.05). SAT and VAT decreased significantly in the liraglutide group and in the insulin glargine group (P < 0.05). ΔSAT and ΔVAT were greater with liraglutide than insulin glargine, they were significantly different between the two groups (ΔSAT, -36 vs. - 24.5, P < 0.05; and ΔVAT, -47 vs. - 16.6, P > 0.05). In the liraglutide group, AST, ALT, and HOMA-IR decreased significantly from baseline. There was no significant difference in glucose-lowering among the three groups. During the treatment, the safety of the three groups performed well.. Compared with placebo, treatment with liraglutide plus an adequate dose of metformin (2000 g/ day) for 26 weeks is more effective in reducing IHCL, SAT and VAT in patients with type 2 diabetes and NAFLD. And it has additional advantages in weight loss, waist circumference reduction and liver function improvement.

Topics: Adult; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Intra-Abdominal Fat; Liraglutide; Liver; Male; Metformin; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Prospective Studies; Subcutaneous Fat; Treatment Outcome; Weight Loss

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.

Topics: Adult; Aged; Blood Glucose; Body Weight; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Linear Models; Lipid Metabolism; Liraglutide; Male; Metformin; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Prognosis; Prospective Studies; Sitagliptin Phosphate; Treatment Outcome

This study assessed the efficacy and safety of iGlarLixi (a titratable, fixed-ratio combination of insulin glargine [iGlar] plus lixisenatide) in older patients with type 2 diabetes.. This post hoc analysis used patient-level data from patients aged ≥65 years from the phase III LixiLan-O and LixiLan-L studies, which compared iGlarLixi with iGlar and lixisenatide (LixiLan-O only). Efficacy endpoints were changes in glycated hemoglobin A1C, fasting plasma glucose, postprandial glucose, weight, and achievement of A1C <7.0% (53 mmol/mol). Safety measures included incidence of documented symptomatic hypoglycemia (defined as typical symptoms of hypoglycemia plus self-measured plasma glucose ≤70 mg/dL [3.9 mmol/L]), severe hypoglycemia (requiring assistance of another person), and incidence of gastrointestinal adverse events. Results were compared with those from patients aged <65 years.. In both trials, older patients treated with iGlarLixi achieved significantly greater reductions in A1C at Week 30 than comparators. Treatment with iGlarLixi mitigated insulin-associated weight gain and lixisenatide-associated gastrointestinal events. Results were largely comparable between patients aged ≥65 versus <65 years.. iGlarLixi provides significant improvements in glycemic control in patients aged ≥65 years without increasing hypoglycemia risk. As a once-daily injection, it simplifies treatment regimens and may contribute to improved adherence in this patient population.

Topics: Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Fasting; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Peptides; Postprandial Period

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 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

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

Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period.. Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or placebo across a spectrum of clinical care, lasted for a preplanned 3years. Participants with uncontrolled hyperglycaemia who met predetermined criteria could receive rescue medication. The ability to remain on study medication without needing additional rescue was an efficacy measure. Glycaemic measures and body weight were analysed in 2 populations: those who remained rescue-free and all participants.. Participants (n=3132) were randomised to albiglutide or comparator. A greater proportion of participants who received albiglutide remained rescue-free (55-71%) compared with placebo (35-51%; p<0.001 to p=0.002). The proportion of rescue-free participants with albiglutide did not differ from glimepiride or insulin glargine, was higher than with sitagliptin (p=0.013), and lower than with pioglitazone (p=0.045). At 3years, albiglutide was associated with clinically significant reductions in hyperglycaemia (eg, rescue-free participants: HbA1c -0.52% [SE0.11] to -0.98% [0.12]; -5.7mmol/mol [1.2] to -10.7mmol/mol [1.3] and all participants: HbA1c -0.29% [0.11] to-0.92% [0.13]; -3.2mmol/mol [1.2] to -10.1mmol/mol [1.4]). Albiglutide was also associated with modest reductions in body weight vs pioglitazone, glimepiride, and insulin glargine, which were associated with weight gain.. These 3-year efficacy data support long-term use of albiglutide in the management of people with T2DM. ClinicalTrials.gov NCT00849056, NCT00849017, NCT00838903, NCT00838916, NCT00839527.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Glargine; Male; Pioglitazone; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Treatment Outcome

This 28-week, randomized, double-blind study compared a once-weekly injection of dulaglutide 1.5 mg to placebo, both added to titrated once-daily insulin glargine (with or without metformin), in patients with type 2 diabetes mellitus and inadequate glycemia control (control defined as hemoglobin A. Patients not naive to injectable therapy were randomly assigned (1:1) to receive dulaglutide/glargine or placebo/glargine; glargine was titrated to a fasting plasma glucose target of 71 to 99 mg/dL. The Impact of Weight on Self-Perceptions (IW-SP), the EQ-5D-5L (measure of health status), the 18-item Diabetes Health Profile (DHP-18), and the Medication Device Delivery Assessment (MDDAB) instruments for assessing the dulaglutide Single-Use Pen (SUP) and glargine-delivery device were administered at baseline and 28 weeks, and also at 6 or 12 weeks for some measures. A mixed model for repeated measures was used for analyzing changes from baseline scores.. At 28 weeks, improvements observed in the transformed total scores on the IW-SP and DHP-18 Disinhibited Eating domain were significantly greater with dulaglutide/glargine compared with placebo/glargine (least squares mean differences, +6.06 [P = 0.019] and -4.50 [P = 0.017], respectively). There were no significant overall between-treatment differences in quality of life as measured by the EQ-5D-5L or the Barriers to Activities and Psychological Distress domains of the DHP-18. Of all patients, 95% reported that overall, the dulaglutide SUP was "easy" or "very easy" to use at 28 weeks. Device-features scores showed that most patients liked the dulaglutide SUP features, with the 3 highest-rated items relating specifically to features of the needle (not having to touch the needle, not having to attach the needle, and automatic insertion). The majority of patients (~90%) "agreed" or "strongly agreed" that they were satisfied with the overall dulaglutide SUP injection experience at 28 weeks.. Dulaglutide/glargine-treated patients had greater improvements in weight-related quality-of-life measures compared with placebo/glargine-treated patients, which may be clinically relevant when evaluating treatment options for insulin-requiring patients who often gain weight with insulin monotherapy. Results from the MDDAB indicated overall satisfaction with the dulaglutide SUP injection experience, which may be an important factor in some patients when initiating parenteral therapy. ClinicalTrials.gov identifier: NCT02152371.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin Glargine; Male; Metformin; Middle Aged; Patient Reported Outcome Measures; Quality of Life; Recombinant Fusion Proteins

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with reduced appetite and body weight. We investigated whether these effects could be mediated by the central nervous system (CNS).. We performed a randomized crossover study in obese patients with type 2 diabetes (n = 20, mean age 59.3 ± 4.1 years, mean BMI 32 ± 4.7 kg/m(2)), consisting of two periods of 12-week treatment with either liraglutide 1.8 mg or insulin glargine. Using functional MRI, we determined the effects of treatment on CNS responses to viewing food pictures in the fasted condition and 30 min after meal intake.. After 12 weeks, the decrease in HbA1c was larger with liraglutide versus insulin glargine (Δ-0.7% vs. -0.2%, P < 0.001). Body weight decreased during liraglutide versus insulin glargine (Δ-3.3 kg vs. 0.8 kg, P < 0.001). After 10 days, patients treated with liraglutide, compared with insulin glargine, showed decreased responses to food pictures in insula and putamen (P ≤ 0.02). In addition, liraglutide enhanced the satiating effect of meal intake on responses in putamen and amygdala (P ≤ 0.05). Differences between liraglutide and insulin glargine were not observed after 12 weeks.. Compared with insulin, liraglutide decreased CNS activation significantly only after short-term treatment, suggesting that these effects of GLP-1RA on the CNS may contribute to the induction of weight loss, but not necessarily to its maintenance, in view of the absence of an effect of liraglutide on CNS activation in response to food pictures after longer-term treatment.

Topics: Blood Glucose; Body Weight; Brain; Cross-Over Studies; Cues; Diabetes Mellitus, Type 2; Fasting; Female; Food; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Liraglutide; Male; Middle Aged; Obesity; Satiation

The aim of the study was to compare body composition and epicardial fat thickness changes in insulin-naïve inadequately controlled patients with type 2 diabetes following basal insulin initiation with detemir vs. glargine. Six-month, open-label, interventional randomized pilot study was conducted. Dual-energy X-ray absorptiometry and echocardiography were used to estimate the body composition and epicardial fat thickness respectively. Thirty-six patients in the detemir group and 20 in the glargine group completed the study. Study groups baseline characteristics were comparable. At 6 months, for similar glycemic control, those on detemir significantly gained less total weight (0.6±2.5 vs. 4.2±4.1 kg, p=0.004), total fat mass (0.9±2.2 vs. 2.9±2.4 kg, p=0.02), and truncal fat mass (0.8±1.5 vs. 2.1±1.7 kg, p=0.02), with a loss in truncal lean mass (- 0.8±1.9 kg vs. 0.3±1.7 kg; p=0.02). EFT significantly decreased from baseline in both group (detemir - 1.7±0.52-mm, glargine - 1.1±1.6-mm; p<0.05, without significant difference inter-groups). Within the detemir group, epicardial fat thickness change correlated with truncal fat and total fat mass changes (r=0.65, p=0.06 and r=0.60, p=0.07). In conclusion, detemir resulted in less fat mass gain, a trend for a more pronounced epicardial fat thickness reduction when compared with glargine.

Topics: Adiposity; Blood Glucose; Body Composition; Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Pericardium

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

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 efficacy and safety of once-weekly dulaglutide 0.75 mg (dulaglutide) in Japanese patients with type 2 diabetes (T2D) were evaluated according to subgroups defined by concomitant oral hypoglycaemic agents. This exploratory analysis included data from a randomized, open-label, phase III study that compared dulaglutide with insulin glargine (glargine) (n = 361). The three subgroups were dulaglutide or glargine in combination with sulphonylurea (SU) alone, biguanide (BG) alone or SU and BG combined. There were no clinically relevant differences in glycated haemoglobin (HbA1c) changes among the three subgroups in the dulaglutide group; in the glargine group, a numerically greater reduction was observed in combination with BG alone compared to the other two groups (SU alone and SU + BG). Weight loss was observed with dulaglutide in combination with BG alone or with SU + BG. The incidence of adverse events among subgroups was significantly different in the glargine group but not in the dulaglutide group. Incidence of hypoglycaemia was highest in combination with SU for both treatments. For patients with T2D, dulaglutide added to concomitant BG may be more likely to result in weight loss than dulaglutide added to concomitant SU.

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

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

The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated.. In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221). The primary endpoint was change from baseline to Week 26 in HbA1c.. After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was -0.08% (-0.26, 0.09 95%CI), confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p < 0.0001) whereas the rate of nocturnal hypoglycemia was 75% lower (p < 0.0001) for IDegAsp versus IGlar.. Nocturnal-confirmed hypoglycemia was higher with IGlar whereas overall and diurnal hypoglycemia were higher with IDegAsp dosed at breakfast. These results highlight the importance of administration of IDegAsp with the main meal of the day, tailored to the individual patient's needs.. ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext].

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Safety

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 compare safety and efficacy of insulin glargine and liraglutide in patients with type 2 diabetes (T2DM).. This randomized, multinational, open-label trial included subjects treated for T2DM with metformin ± sulphonylurea, who had glycated haemoglobin (HbA1c) levels of 7.5-12%. Subjects were assigned to 24 weeks of insulin glargine, titrated to target fasting plasma glucose of 4.0-5.5 mmol/L or liraglutide, escalated to the highest approved clinical dose of 1.8 mg daily. The trial was powered to detect superiority of glargine over liraglutide in percentage of people reaching HbA1c <7%.. The mean [standard deviation (s.d.)] age of the participants was 57 (9) years, the duration of diabetes was 9 (6) years, body mass index was 31.9 (4.2) kg/m(2) and HbA1c level was 9.0 (1.1)%. Equal numbers (n = 489) were allocated to glargine and liraglutide. Similar numbers of subjects in both groups attained an HbA1c level of <7% (48.4 vs. 45.9%); therefore, superiority of glargine over liraglutide was not observed (p = 0.44). Subjects treated with glargine had greater reductions of HbA1c [-1.94% (0.05) and -1.79% (0.05); p = 0.019] and fasting plasma glucose [6.2 (1.6) and 7.9 (2.2) mmol/L; p < 0.001] than those receiving liraglutide. The liraglutide group reported a greater number of gastrointestinal treatment-emergent adverse events (p < 0.001). The mean (s.d.) weight change was +2.0 (4.0) kg for glargine and -3.0 (3.6) kg for liraglutide (p < 0.001). Symptomatic hypoglycaemia was more common with glargine (p < 0.001). A greater number of subjects in the liraglutide arm withdrew as a result of adverse events (p < 0.001).. Adding either insulin glargine or liraglutide to subjects with poorly controlled T2DM reduces HbA1c substantially, with nearly half of subjects reaching target levels of 7%.

Topics: Administration, Oral; Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; International Cooperation; Liraglutide; Male; Metformin; Middle Aged; 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

Glycemic variability may contribute to adverse medical outcomes of type 2 diabetes, but prior therapies have had limited success in controlling glycemic fluctuations, and the hypothesis has not been adequately tested.. People with insulin-requiring type 2 diabetes and high cardiovascular risk were enrolled during a run-in period on basal-bolus insulin (BBI), and 102 were randomized to continued BBI or to basal insulin with a prandial GLP-1 receptor agonist (GLIPULIN) group, each seeking to maintain HbA(1c) levels between 6.7% and 7.3% (50-56 mmol/mol) for 6 months. The primary outcome measure was glycemic variability assessed by continuous glucose monitoring; other measures were HbA(1c), weight, circulating markers of inflammation and cardiovascular risk, albuminuria, and electrocardiographic patterns assessed by Holter monitoring.. At randomization, the mean age of the population was 62 years, median duration of diabetes 15 years, mean BMI 34 kg/m(2), and mean HbA(1c) 7.9% (63 mmol/mol). Thirty-three percent had a prior cardiovascular event, 18% had microalbuminuria, and 3% had macroalbuminuria. At baseline, the continuous glucose monitoring coefficient of variation for glucose levels was similar in both groups.. FLAT-SUGAR is a proof-of-concept study testing whether, in a population of individuals with type 2 diabetes and high cardiovascular risk, the GLIPULIN regimen can limit glycemic variability more effectively than BBI, reduce levels of cardiovascular risk markers, and favorably alter albuminuria and electrocardiographic patterns. We successfully randomized a population that has sufficient power to answer the primary question, address several secondary ones, and complete the protocol as designed.

Topics: Albuminuria; Biomarkers; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exenatide; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Peptides; Postprandial Period; Risk Factors; Time Factors; Venoms

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

Our aim was to compare the effects of an intermediate acting human insulin (NPH) and a long-acting insulin analog, insulin glargine, in insulin naïve type 2 diabetes patients, stratified by the type of hyperglycemia (fasting or postprandial type). Based on different action profiles, we hypothesized that patients having different hyperglycemia types would react differently when treated with these insulins. This is a post hoc analysis of the Lanmet study data. The Lanmet study was a randomized, 36-week controlled insulin initiation study in type 2 diabetes patients. 109 subjects with baseline HbA1c >8.0% (64 mmol/mol) completed the study. The patients were divided into two groups according to fasting glucose (mmol/l)/HbA1c (%) ratio. Patients with a ratio ≥1.3 were defined as having fasting type and those with a ratio <1.3 as having postprandial type hyperglycemia. The main outcome measures were change in HbA1c and body weight, and final insulin dose. Independently of insulin type, compared to patients with postprandial type hyperglycemia, those with fasting type hyperglycemia had 2.1 kg/m(2) greater initial BMI (p = 0.044), gained 2.0 kg more weight (p = 0.020, adjusted for baseline BMI p = 0.035), and had 36% greater final insulin dose/kg (p = 0.001). With respect to hyperglycemia type, there was no difference between NPH and glargine in their effects on HbA1c. When starting bedtime insulin in type 2 diabetes patients, those with fasting type hyperglycemia are prone to greater weight gain. Hyperglycemia type does not help in identifying patients who would benefit specially from either NPH insulin or insulin glargine.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Statistics, Nonparametric

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

Glucose fluctuation often remains to be corrected under basal-supported oral therapy. We investigated the efficacy of adding once-daily rapid-acting insulin in Japanese diabetes patients treated with basal-supported oral therapy.. In this 8-week, parallel-group, randomized, open-label trial, 62 Japanese adults with type 2 diabetes treated with insulin glargine and 50 mg of sitagliptin were randomized into the following two arms: the single-bolus group, in which once-daily insulin glulisine was initiated at a main meal at a fifth (i.e., 20%) the dose of insulin glargine, and the control group, in which the dose of sitagliptin was maximized to 100 mg. The primary end point was the change of glycemic fluctuation assessed with the M-value.. Baseline hemoglobin A1c levels, mean blood glucose profiles, and M-value were 7.2 ± 0.6%, 9.3 ± 1.7 mmol/L, and 21 ± 13 units, respectively. At the end of the study, the single-bolus group had a greater reduction of M-value than the control group (P=0.02); the difference was 6.5 units (95% confidence interval, 1.1-11.9 units). The single-bolus group also had a greater reduction of mean blood glucose levels (P=0.01). There were no significant differences in the incidence of hypoglycemia or the weight change between the two groups (P>0.05).. Adding once-daily insulin glulisine was more effective in controlling the glycemic fluctuation in Japanese type 2 diabetes patients treated with insulin glargine together with sitagliptin.

Topics: Adult; Asian People; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Triazoles

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

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

Most studies report using percentage of total daily insulin (TDI) for converting therapy from continuous insulin infusion to subcutaneous insulin in cardiac surgery patients. Few studies have evaluated the efficacy of using body weight to calculate the basal insulin dose.. To compare the efficacy and safety of dosing insulin glargine by weight versus percentage of TDI in cardiac surgery patients transitioning from continuous insulin infusion to subcutaneous insulin.. We conducted a prospective, randomized, open-label, pilot study. Study patients who had a preoperative weight less than 100 kg and were receiving at least 6 hours of a continuous insulin infusion were randomized to receive either 50% of their TDI requirement or 0.5 units/kg of glargine as a one-time dose 2 hours before stopping the continuous insulin infusion. All patients were administered subcutaneous corrective insulin. Blood glucose monitoring occurred before each meal, at bedtime, and with morning laboratory tests for 24 hours after administration of the glargine dose.. A total of 200 blood glucose measurements were performed in each group. The percentage of blood glucose measurements in target range (80-140 mg/dL) was similar between the weight-based group and the percentage-based group (66% vs 64%, p = 0.75). Median blood glucose after transition was 120 mg/dL (interquartile range [IQR] 99-147) in the weight-based group compared to 127 mg/dL (IQR 107-149; p = 0.03) in the percentage-based group. The median glargine dose was higher in the weight-based group (41 units; IQR 36-44) than in the weight-based group (24 units; IQR 14-30, p < 0.001). The rate of hypoglycemia (blood glucose <60 mg/dL) was 2.5% in each group.. In this small cohort, dosing insulin glargine by weight proved to be safe, but larger scale studies are needed before adopting weight-based dosing in this patient population.

Topics: Aged; Aged, 80 and over; Blood Glucose; Body Weight; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Infusions, Intravenous; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Pilot Projects; Prospective Studies

In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative. We aimed to compare the efficacy, tolerability, and safety of insulin glargine and sitagliptin, a DPP-4 inhibitor, in patients whose disease was uncontrolled with metformin.. In this comparative, parallel, randomised, open-label trial, metformin-treated people aged 35-70 years with glycated haemoglobin A(1c) (HbA(1c)) of 7-11%, diagnosis of type 2 diabetes for at least 6 months, and body-mass index of 25-45 kg/m(2) were recruited from 17 countries. Participants were randomly assigned (1:1) to 24-week treatment with insulin glargine (titrated from an initial subcutaneous dose of 0·2 units per kg bodyweight to attain fasting plasma glucose of 4·0-5·5 mmol/L) or sitagliptin (oral dose of 100 mg daily). Randomisation (via a central interactive voice response system) was by random sequence generation and was stratified by centre. Patients and investigators were not masked to treatment assignment. The primary outcome was change in HbA(1c) from baseline to study end. Efficacy analysis included all randomly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable. This trial is registered at ClinicalTrials.gov, NCT00751114.. 732 people were screened and 515 were randomly assigned to insulin glargine (n=250) or sitagliptin (n=265). At study end, adjusted mean reduction in HbA(1c) was greater for patients on insulin glargine (n=227; -1·72%, SE 0·06) than for those on sitagliptin (n=253; -1·13%, SE 0·06) with a mean difference of -0·59% (95% CI -0·77 to -0·42, p<0·0001). The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin (4·21 [SE 0·54] vs 0·50 [SE 0·09] events per patient-year; p<0·0001). Severe hypoglycaemia occurred in only three (1%) patients on insulin glargine and one (<1%) on sitagliptin. 15 (6%) of patients on insulin glargine versus eight (3%) on sitagliptin had at least one serious treatment-emergent adverse event.. Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin. Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease.. Sanofi.

Topics: Adult; Aged; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles

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

Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A₁(c) (HbA₁(c)) targets.. To test whether twice-daily exenatide injections reduce HbA₁(c) levels more than placebo in people receiving insulin glargine.. Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA₁(c) level at site, performed from October 2008 to January 2010. Participants, investigators, and personnel conducting the study were masked to treatment assignments. (ClinicalTrials.gov registration number: NCT00765817). 59 centers in 5 countries.. Adults with type 2 diabetes and an HbA₁(c) level of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents).. Assignment by a centralized, computer-generated, random-sequence interactive voice-response system to exenatide, 10 µg twice daily, or placebo for 30 weeks.. The primary outcome was change in HbA₁(c) level. Secondary outcomes included the percentage of participants with HbA₁(c) values of 7.0% or less and 6.5% or less, 7-point self-monitored glucose profiles, body weight, waist circumference, insulin dose, hypoglycemia, and adverse events.. 112 of 138 exenatide recipients and 101 of 123 placebo recipients completed the study. The HbA₁(c) level decreased by 1.74% with exenatide and 1.04% with placebo (between-group difference, -0.69% [95% CI, -0.93% to -0.46%]; P < 0.001). Weight decreased by 1.8 kg with exenatide and increased by 1.0 kg with placebo (between-group difference, -2.7 kg [CI, -3.7 to -1.7]). Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d. The estimated rate of minor hypoglycemia was similar between groups. Thirteen exenatide recipients and 1 placebo recipient discontinued the study because of adverse events (P < 0.010); rates of nausea (41% vs. 8%), diarrhea (18% vs. 8%), vomiting (18% vs. 4%), headache (14% vs. 4%), and constipation (10% vs. 2%) were higher with exenatide than with placebo.. The study was of short duration. There were slight imbalances between groups at baseline in terms of sex, use of concomitant glucose-lowering medications, and HbA₁(c) levels, and more exenatide recipients than placebo recipients withdrew because of adverse events.. Adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine treatment. Adverse events of exenatide included nausea, diarrhea, vomiting, headache, and constipation.. Alliance of Eli Lilly and Company and Amylin Pharmaceuticals.

Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Peptides; Pioglitazone; Sensitivity and Specificity; Thiazolidinediones; Venoms

We previously showed that exenatide (EXE) enhanced insulin secretion after 1 year of treatment, relative to insulin glargine (GLAR), with a similar glucose-lowering action. These effects were not sustained after a 4-week off-drug period. This article reports the results after additional 2 years of exposure.. Sixty-nine metformin-treated patients with type 2 diabetes were randomized to EXE or GLAR. Forty-six patients entered the 2-year extension study in which they continued their allocated therapy. Thirty-six completed (EXE: n = 16; GLAR: n = 20) the 3-year exposure period. Insulin sensitivity (M value) and β-cell function were measured by euglycemic hyperinsulinemic clamp followed by hyperglycemic clamp with arginine stimulation at pretreatment (week 52) and 4 weeks after discontinuation of study medication (week 56 and week 172). First-phase glucose stimulated C-peptide secretion was adjusted for M value and calculated as the disposition index (DI).. At 3 years, EXE and GLAR resulted in similar levels of glycemic control: 6.6 ± 0.2% and 6.9 ± 0.2%, respectively (P = 0.186). EXE compared with GLAR significantly reduced body weight (-7.9 ± 1.8 kg; P < 0.001). After the 4-week off-drug period, EXE increased the M value by 39% (P = 0.006) while GLAR had no effect (P = 0.647). Following the 4-week off-drug period, the DI, compared with pretreatment, increased with EXE, but decreased with GLAR (1.43 ± 0.78 and -0.99 ± 0.65, respectively; P = 0.028).. EXE and GLAR sustained HbA(1c) over the 3-year treatment period, while EXE reduced body weight and GLAR increased body weight. Following the 3-year treatment with EXE, the DI was sustained after a 4-week off-drug period. These findings suggest a beneficial effect on β-cell health.

Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin-Secreting Cells; Insulin, Long-Acting; Male; Metformin; Middle Aged; Peptides; Venoms

To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers.. Metformin-treated patients with type 2 diabetes (N = 69) were randomized to exenatide or insulin glargine and treated for 1 year. Body composition was evaluated by dual-energy X-ray absorptiometry. Additionally, body weight, waist circumference, and cardiovascular biomarkers were measured.. Treatment with exenatide for 1 year significantly reduced body weight, waist circumference, and total body and trunkal fat mass by 6, 5, 11, and 13%, respectively. In addition, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. Insulin glargine significantly reduced endothelin-1 by 7%. These changes were statistically independent of the change in total body fat mass and body weight.. Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk. No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels.

Topics: Absorptiometry, Photon; Adiponectin; Body Composition; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Endothelin-1; Exenatide; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Peptides; Risk Factors; Venoms; Waist Circumference

To explore glucose lowering response to insulin initiation or switch to insulin glargine in obese and non-obese individuals with type 2 diabetes mellitus (T2DM) and to examine weight gain and hypoglycaemic episodes in this group.. Post hoc subgroup analysis using data of obese and non-obese participants from a large multi-centre (4555 participants with T2DM), multi-national 24-week randomized controlled trial of investigator titrated insulin glargine versus patient self-managed titrated insulin glargine. This analysis was carried out to compare two subgroups: obese (> or =30 kg/m2) and non-obese (<30 kg/m2) participants.. The mean body mass index (BMI) values were 33.7 kg/m2(n = 1833) and 25.9 kg/m(2)(n = 2755) in obese and non-obese subjects, respectively. There was a significant reduction in glycated haemoglobin (HbA1c) from baseline in both subgroups but no significant difference between subgroups (1.15 vs. 1.15%, p = 0.50). Overall, there was a 1.21 kg (s.d. 3.3) increase in weight in individuals who were non-obese and a 1.08 kg (s.d. 3.9) increase in obese individuals (p = 0.67). There was no significant difference in the proportion of participants achieving an HbA1c of <7.0% at 6 months in both the subgroups (28.8 vs. 27.1%, p = 0.20). In multiple logistic regression, BMI was not a prognostic factor in achieving a target of HbA1c < or = 7.0%. There was no significant difference in severe hypoglycaemic episodes between obese and non-obese subgroups (1.3 vs. 1.0%); however, significantly more non-obese individuals experienced nocturnal hypoglycaemic episodes(4.5 vs. 2.4%, p < 0.05).. In this study, treatment with insulin glargine in people with T2DM was associated with a significant reduction in HbA1c without differential increase in weight gain in obese and non-obese subgroups. Rates of severe hypoglycaemia were not different between obese and non-obese subgroups.

Topics: Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity; Treatment Outcome

Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI).. Patients (type 2 diabetes, aged 30-75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose <7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose <6.7 mmol/l).. A total of 1,115 patients were randomly assigned (PRANDIAL n = 557; BASAL n = 558), and the mean patient participation after randomization was 963 days (range 1-1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n = 174, 31.2%) and BASAL (n = 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8-1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 +/- 0.1 vs. 7.8 +/- 0.1%; P = 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P < 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P < 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P < 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P = 0.233) versus the PRANDIAL group.. Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.

Topics: Adult; Aged; Body Weight; Cardiovascular System; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Risk Factors; Treatment Outcome

The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride.. This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times.. The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies.. Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin.. ClinicalTrials.gov NCT00331851.. The study was funded by Novo Nordisk A/S.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Metformin; Middle Aged; Placebos; Sulfonylurea Compounds; Young Adult

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

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

Intensification of insulin therapy in patients with type 2 diabetes, while improving glycemic control, often leads to an increase in body weight and other markers of cardiovascular risk. The effects of pramlintide as an adjunct to basal insulin titration (without mealtime insulin) on glycemia and cardiovascular risk markers were examined.. This was a post hoc analysis of a 16-week, double-blind, placebo-controlled study in patients with type 2 diabetes (N = 211) using insulin glargine (without mealtime insulin) +/- oral agents. Patients were randomized to treatment with placebo or pramlintide (60 or 120 mug with major meals), and insulin glargine was titrated to target a fasting plasma glucose concentration of > or = 70 to < 100 mg/dL.. Endpoints included the change from baseline to Week 16 in body weight, high sensitivity C-reactive protein (hsCRP), triglycerides, HDL, LDL, and blood pressure.. Pramlintide-treated patients lost weight and placebo-treated patients gained weight during 16 weeks of treatment (-1.6 +/- 0.3 kg vs. +0.7 +/- 0.3 kg, p < 0.001; mean +/- SE). hsCRP was reduced in pramlintide-treated versus placebo-treated patients (-0.8 +/- 0.2 mg/L vs. 0.1 +/- 0.2 mg/L, p < 0.01; mean +/- SE). Patients with baseline hsCRP > 3 mg/L (high cardiovascular risk) demonstrated greater hsCRP reductions with pramlintide versus placebo treatment at Week 16 (p < 0.05). Patients with baseline triglycerides > or = 150 mg/dL or > or = 200 mg/dL (high cardiovascular risk) showed significant reductions from baseline in triglyceride concentrations with pramlintide (-43 +/- 14 mg/dL or -59 +/- 19 mg/dL; p < 0.05; mean +/- SE) but not with placebo (1 +/- 29 mg/dL or -3 +/- 54 mg/dL; mean +/- SE). No significant differences between pramlintide and placebo were observed for changes in HDL, LDL, or blood pressure. Pramlintide treatment was generally well tolerated. The most frequent adverse event related to pramlintide was mild-to-moderate nausea (31% pramlintide vs. 10% placebo). Pramlintide added to basal insulin did not increase the incidence of hypoglycemia. A limitation of the study was its relatively short duration.. Pramlintide, as an adjunct to basal insulin, was associated with improvements in several cardiovascular risk markers, warranting long-term clinical studies to determine its potential effects on cardiovascular risk.

Topics: Aged; Amyloid; Biomarkers; Blood Glucose; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Islet Amyloid Polypeptide; Male; Middle Aged; Placebos; Risk Factors; Triglycerides

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

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

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

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

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 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

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

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

Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs).. This 28-week parallel-group study randomized 233 insulin-naive patients with HbA(1c) values >/=8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5-6 units BIAsp 70/30 twice daily or 10-12 units glargine at bedtime and titrated to target blood glucose (80-110 mg/dl) by algorithm-directed titration.. A total of 209 subjects completed the study. At study end, the mean HbA(1c) value was lower in the BIAsp 70/30 group than in the glargine group (6.91 +/- 1.17 vs. 7.41 +/- 1.24%, P < 0.01). The HbA(1c) reduction was greater in the BIAsp 70/30 group than in the glargine group (-2.79 +/- 0.11 vs. -2.36 +/- 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA(1c) >8.5% (-3.13 +/- 1.63 vs. -2.60 +/- 1.50%, respectively; P < 0.05). More BIAsp 70/30-treated subjects reached target HbA(1c) values than glargine-treated subjects (HbA(1c) 8.5%.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Treatment Outcome

To study the effects of exercise on the absorption of the basal long-acting insulin analog insulin glargine (Lantus), administered subcutaneously in individuals with type 1 diabetes.. A total of 13 patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen were studied. (125)I-labeled insulin glargine at the usual basal insulin dose was injected subcutaneously into the thigh on the evening (2100) before the study day on two occasions 1 week apart. Patients were randomly assigned to 30 min intense exercise (65% peak oxygen uptake [Vo(2peak)]) on one of these visits. The decay of radioactive insulin glargine was compared on the two occasions using a thallium-activated Nal gamma counter. Blood samples were collected at regular intervals on the study days to assess plasma glucose and insulin profiles.. No significant difference was found in the (125)I-labeled insulin glargine decay rate on the two occasions (exercise vs. no exercise; repeated-measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was observed over the exercise period (area under curve above fasting [DeltaAUC] glucose: -0.39 +/- 0.11 vs. -1.30 +/- 0.16 mmol . l(-1) . h(-1); nonexercise vs. exercise; P = 0.001), but insulin levels did not differ significantly on the two occasions (DeltaAUC insulin: -2.1 +/- 3.9 vs. 1.5 +/- 6.2 pmol . l(-1) . h(-1); nonexercise versus exercise; P = 0.507).. An intense 30-min period of exercise does not increase the absorption rate of the subcutaneously injected basal long-acting insulin analog insulin glargine in patients with type 1 diabetes.

Topics: Absorption; Adolescent; Adult; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Diabetes Mellitus, Type 1; Exercise; Female; Humans; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

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

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

To evaluate the real-world effectiveness and safety of insulin glargine 300 U/ml (Gla-300) in achieving glycaemic goals in insulin-naïve people with type 2 diabetes (T2D) in Mexico, Colombia and Peru (Latin America region) in the A Toujeo Observational Study (ATOS).. ATOS was a multicentre, prospective, 12-month observational study, which included 4422 insulin-naïve adults (age ≥ 18 years) with T2D uncontrolled (HbA1c > 7% and ≤11%) on at least one oral antidiabetic drug (OAD) who initiated Gla-300 treatment as per routine practice. The primary endpoint was the percentage of participants achieving their predefined individualized HbA1c goal at month 6. Key secondary endpoints included change from baseline in HbA1c, fasting plasma glucose (FPG), fasting self-monitored blood glucose (SMBG), body weight and incidence of hypoglycaemia.. In this subgroup analysis, a total of 314 participants with T2D received Gla-300. At baseline, mean ± SD age was 56.0 ± 11.6 years, duration of diabetes was 9.7 ± 6.6 years and 65.9% of participants were on at least two OADs. The individualized HbA1c target was achieved by 25.8% of participants (95% confidence interval [CI]: 20.3-31.9) at month 6 and by 35.3% (95% CI: 28.5-42.5) at month 12. Gla-300 treatment improved glycaemic control with meaningful reductions in mean HbA1c, FPG and fasting SMBG. The incidence of hypoglycaemia reported was low and body weight remained stable.. In a real-world setting in the Latin America region, the initiation of Gla-300 in people with T2D uncontrolled on OADs resulted in improved glycaemic control with a low incidence of hypoglycaemia and no change in body weight.

Topics: Adolescent; Adult; Aged; Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Glargine; Middle Aged; Prospective Studies

Tirzepatide reduces HbA1c and body weight, and creatinine-based estimated glomerular filtration rate (eGFR) decline. Unlike creatine-derived eGFR (eGFR-creatinine), cystatin C-derived eGFR (eGFR-cystatin C) is unaffected by muscle mass changes. We assessed effects of tirzepatide on eGFR-creatinine and eGFR-cystatin C.. Our primary outcome was eGFR change from baseline at 52 weeks with pooled tirzepatide (5, 10, and 15 mg) and titrated insulin glargine in adults with type 2 diabetes and high cardiovascular risk (SURPASS-4).. Least squares mean (SE) eGFR-creatinine (mL/min/1.73 m2) changes from baseline with tirzepatide and insulin glargine were -2.5 (0.38) and -3.9 (0.38) (between-group difference, 1.4 [95% CI 0.3-2.4]) and -3.5 (0.37) and -5.3 (0.37) (between-group difference, 1.8 [95% CI 0.8-2.8]) for eGFR-cystatin C. Baseline, 1-year, and 1-year change from baseline values significantly correlated between eGFR-cystatin C and eGFR-creatinine. Measures of eGFR changes did not correlate with body weight changes.. Tirzepatide slows the eGFR decline rate, supporting a kidney-protective effect.

Topics: Adult; Body Weight; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Humans; Insulin Glargine; Kidney

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

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

A post-hoc analysis to assess the impact in people with type 2 diabetes, of increasing doses of basal insulin on glycaemic measures, body weight and hypoglycaemia.. We included data from prospective, randomized controlled treat-to-target trials of ≥24 weeks' duration in people with type 2 diabetes, uncontrolled on metformin and sulphonylureas, and treated with insulin glargine 100 units/mL (U100), who had at least six fasting plasma glucose (FPG) measurements. The impact of insulin dose on glycated haemoglobin (HbA1c) values, FPG, hypoglycaemia incidence (<3.9 mmol/L [70 mg/dL]), and body weight was analysed. A total of 458 participants from three eligible trials were included.. The observed relationship between higher basal insulin doses and glycaemic control was non-linear, with increasing insulin dose leading to smaller reductions in FPG and HbA1c for doses >0.3 IU/kg/d, with a plateauing effect at 0.5 IU/kg/d. Total daily dose of insulin >0.5 IU/kg/d resulted in greater weight gain, but without higher rates of hypoglycaemia, compared with insulin doses ≤0.5 IU/kg/d.. This analysis indicates that basal insulin doses >0.5 IU/kg/d have diminishing additional impact on improving glycaemic measures, with the disadvantage of additional weight gain. Clinicians should consider anti-hyperglycaemic treatment intensification at doses approaching 0.5 IU/kg/d.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Humans; Insulin Glargine; Male; Middle Aged; Postprandial Period; Randomized Controlled Trials as Topic

We sincerely thank Dr. Sikarin Upala for his interest in our article and for sharing his experience in the treatment of nonalcoholic fatty liver disease (NAFLD). NAFLD is prevalent in patients with type 2 diabetes mellitus (T2DM), yet only preliminary evidence are available on the effect of anti-diabetic agents to NAFLD in T2DM patients. According to clinical practice guidelines for NAFLD management

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

We read with interest a recent article written by Yan et al.

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Incretins; Insulin Glargine; Lipids; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate

Newly diagnosed pediatric patients with type 1 diabetes mellitus (T1D) can be underweight, overweight, or normal weight at presentation. Study objectives were to determine if, across weight categories, admission body weight (ABW)-based initial insulin glargine dosing resulted in similar fasting blood glucose responses on day of discharge, how initial ABW-based doses differed from doses at outpatient follow-up, and whether an ideal body weight (IBW) would provide a better estimate of body weight after discharge.. Retrospective chart review.. Urban tertiary academic medical center.. Eighty-one pediatric patients newly diagnosed with T1D who started therapy with subcutaneous insulin glargine between October 2014 and October 2016; patients were categorized by weight using body mass index (BMI) percentiles (underweight, normal weight, or overweight/obese).. Data on patient parameters from hospitalization to outpatient physician follow-up were collected. The McLaren, Moore, and BMI IBW methods were used to calculate IBW for each patient; these IBWs were compared with weights at outpatient follow-up. Initial insulin glargine doses were similar among all weight groups: median (range) 0.299 (0.227-0.4), 0.297 (0.204-0.421), and 0.291 (0.194-0.394) units/kg/dose, respectively, for the underweight, normal weight, and overweight/obese groups. No significant differences in discharge fasting glucose level or insulin glargine dose change from admission to first outpatient follow-up visit were noted. Underweight patients gained significantly more weight within 60 days after discharge compared with normal and overweight/obese patients, (median 16.3% vs 7.7% and 5.7%, respectively; p=0.002), aligning closest with the McLaren IBW. ABW was the best estimate of weight at outpatient follow-up in the overweight/obese patient group.. For children who presented underweight, the McLaren IBW method was the best predictor of outpatient dose and body weight, whereas ABW was the best estimate in overweight and obese patients. Further investigation of the role of IBW- or ABW-based dosing methods in underweight pediatric patients with T1D may assist in optimal dosing.

Topics: Academic Medical Centers; Adolescent; Blood Glucose; Body Mass Index; Body Weight; Child; Child, Preschool; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Medical Records; Overweight; Retrospective Studies; Thinness

The Restoring Insulin Secretion (RISE) Adult Medication Study compared pharmacological approaches targeted to improve β-cell function in individuals with impaired glucose tolerance (IGT) or treatment-naive type 2 diabetes of <12 months duration.. All three active treatments produced on-treatment reductions in weight and improvements in HbA. In adults with IGT or recently diagnosed type 2 diabetes, interventions that improved β-cell function during active treatment failed to produce persistent benefits after treatment withdrawal. These observations suggest that continued intervention may be required to alter the progressive β-cell dysfunction in IGT or early type 2 diabetes.

Topics: Adult; Arginine; B-Lymphocytes; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Liraglutide; Male; Metformin; Middle Aged; Withholding Treatment

iGlarLixi is a titratable, fixed-ratio combination of insulin glargine (iGlar, 100 units/ml) and the glucagon-like peptide-1 receptor agonist lixisenatide for the treatment of patients with type 2 diabetes. This post hoc analysis of the phase 3 LixiLan-L trial (NCT02058160) investigated baseline characteristics, glycemic control, and safety outcomes in participants who received the study-specified maximum dose (60 units/day) of iGlarLixi or iGlar vs. those who received < 60 units/day.. Outcomes were compared for participants receiving 60 or < 60 units/day at week 30. Endpoints analyzed included change in A1C, fasting plasma glucose (FPG), 2-h postprandial glucose (2-h PPG), body weight, proportion of participants achieving A1C < 7.0%, proportion of participants receiving rescue therapy, documented symptomatic hypoglycemia, and gastrointestinal adverse event (GI AE) incidence.. By week 30, 27% (iGlarLixi) and 31% (iGlar) of participants received the maximum dose. Participants on 60 vs. < 60 units/day were younger and had higher body weight, body mass index (BMI), FPG, and baseline insulin dose. In both dose groups, A1C change from baseline was significantly greater with iGlarLixi vs. iGlar, and more participants treated with iGlarLixi vs. iGlar achieved A1C < 7.0%. No significant differences were observed in change from baseline for A1C, FPG, 2-h PPG, or GI AE incidence between insulin dose groups, regardless of treatment. In both treatment arms, incidence of symptomatic hypoglycemia was lower in participants receiving 60 units/day vs. those receiving < 60 units/day. Participants treated with iGlarLixi (< 60 or 60 units/day) had modest weight loss over 30 weeks vs. an increase in weight compared with iGlar.. Maximum doses of iGlarLixi were required in participants with a more insulin-resistant clinical phenotype (younger, higher BMI, FPG, and insulin doses). Benefits were observed with iGlarLixi vs. iGlar, even at 60 units/day, with more participants achieving glycemic goals, no increase in symptomatic hypoglycemia, and a modest reduction in body weight.. Sanofi US, Inc.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Peptides; Postprandial Period; Weight Loss

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

BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age. Body weight, pancreatic weight, levels of blood glucose, triacylglycerol, C-peptide, and the intraperitoneal glucose tolerance test (IPGTT) were used. Expression levels of the INS1 gene were measured using reverse transcription polymerase chain reaction (RT-PCR), and pancreatic and duodenal homeobox 1 (Pdx1), paired box 4 (Pax4), and paired box 6 (Pax6) mRNA expression were measured. RESULTS Both insulin glargine and liraglutide improved glycemic control of db/db mice when compared with vehicle. The following were significantly increased in the HLG compared with the GG: the receiver operating characteristic (ROC) area under the curve (AUC) for the IPGTT; C-peptide levels; the pancreas to body weight coefficient; expression levels of the INS1 gene and pancreatic transcription factors Pdx1, Pax4 and Pax6. Liraglutide treatment was without hypoglycemic effects. CONCLUSIONS Liraglutide acted in a dose-dependent manner on glycemic control of db/db mice, and was more effective than insulin glargine, when administered at a high dose.

Topics: Animals; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Glucose Tolerance Test; Hypoglycemic Agents; Insulin Glargine; Insulin-Secreting Cells; Liraglutide; Male; Mice; RNA, Messenger; Triglycerides; Up-Regulation

The aim was to compare changes in HbA1c and body weight after initiation of dapagliflozin or basal insulin supported oral therapy (BOT) in type 2 diabetes patients in primary care practices.. Patients from 983 primary care practices who started dapagliflozin or BOT between December 2012 and July 2015 (index date, ID) were retrospectively analyzed (Disease Analyzer; Germany). Changes in HbA1c (%) and body weight (kg) were evaluated 90-270 days after ID. Propensity score (PS) matching (1:1) was used to adjust for differences in baseline clinical characteristics (180-0 days before ID: age, sex, health insurance, diabetologist care, glucose lowering therapy, HbA1c, body mass index) and duration (days) between start of therapies and last HbA1c or weight documentation after ID.. After PS matching, 766 dapagliflozin (mean ± SD; age: 63 ± 10 years; HbA1c: 8.9 ± 1.2%) and 766 BOT (age: 63 ± 10 years; HbA1c: 8.7 ± 1.1%) patients were included. HbA1c decreased by mean (SD) of 1.0% (1.3) in dapagliflozin and by 1.0% (1.4) in BOT patients after 90-270 days (HbA1c reduction; dapagliflozin vs BOT: -0.01%; P = .79). In 440 dapagliflozin users with available data, body weight (97.4 ± 19.9 kg) decreased by 3.1 (5.8) kg after 90-270 days, whereas no significant weight change was observed in 440 matched BOT patients (97.5 ± 19.9 kg) (weight reduction; dapagliflozin vs BOT: -3.0 kg; P < .05).. Initiation of dapagliflozin therapy reduced HbA1c similar to basal insulin with the additional benefit of weight reduction in type 2 diabetes patients treated in general practices.

Topics: Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Primary Health Care; Retrospective Studies

This post hoc analysis assessed the evidence behind common reimbursement practices by evaluating the relationship of body mass index (BMI) ranges (<30, 30-35 and >35 kg/m(2) ) with treatment effects of exenatide twice daily among patients with type 2 diabetes. Patients received exenatide twice daily added to insulin glargine in two 30-week studies (exenatide twice daily vs insulin lispro, n = 627; exenatide twice daily vs placebo, n = 259). No association of baseline BMI with changes in efficacy variables was observed. Glycated haemoglobin (HbA1c) reductions were significant (p < 0.0001) and similar across BMI range groups in the lispro-comparator study and greater for exenatide versus placebo in the placebo-controlled study. Significant weight loss occurred with exenatide across BMI range groups (p < 0.0001), while weight increased with both comparators. Achievement of HbA1c <7.0% (<53 mmol/mol) without weight gain was greater for exenatide versus comparators. Systolic blood pressure decreased across BMI range groups with exenatide in the lispro-comparator study (p < 0.0001); changes in lipids were not clinically meaningful. Minor hypoglycaemia was less frequent for exenatide versus insulin lispro. These findings suggest that BMI alone should not limit clinical decision-making or patient access to medication.

Topics: Aged; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Female; Glycated Hemoglobin; Humans; Insulin Glargine; Insulin Lispro; Male; Middle Aged; Obesity; Peptides; Randomized Controlled Trials as Topic; Treatment Outcome; Venoms

It is known that after pancreatectomy, patients experience hyposecretion of endogenous insulin and frequently develop diabetes. However, it has been unclear whether combination therapy with glucagon-like peptide-1 receptor agonists and basal insulin is effective for such patients. In the present study, we evaluated the efficacy and safety of combination therapy with long-acting insulin glargine and the glucagon-like peptide-1 receptor agonist lixisenatide in patients who developed diabetes after pancreatectomy.. Japanese patients who developed diabetes after pancreatectomy were eligible for this study. Participants were treated with combination therapy of glargine and lixisenatide for 12 weeks. Fasting and postprandial plasma glucose, C-peptide immunoreactivity, glycated hemoglobin, bodyweight, visceral fat and subcutaneous fat were measured.. At 12 weeks after initiation of lixisenatide, glycated hemoglobin levels decreased from 8.46 ± 1.64% to 6.81 ± 1.15%. In addition, 1-h postprandial plasma glucose and 2-h postprandial plasma glucose levels significantly decreased from 222.9 ± 56.2 mg/dL to 125.1 ± 37.5 mg/dL (P < 0.001) and from 247.5 ± 56.8 mg/dL to 115.1 ± 29.0 mg/dL (P < 0.001), respectively. Neither hypoglycemia nor clinically relevant adverse events occurred during this study.. The present study shows that combination therapy with basal insulin and glucagon-like peptide-1 receptor agonists after partial pancreatectomy can be a useful therapeutic option for providing effective glycemic control with a reduced risk of hypoglycemia.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Japan; Male; Pancreatectomy; Peptides; Postoperative Complications; Postprandial Period; Risk; Treatment Outcome

Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Liver; Macrophages; Male; Omentum; Rats; Rats, Inbred Lew; Reactive Oxygen Species

Rates of confirmed and severe, as well as nocturnal, hypoglycemia are generally lower with insulin glargine U-300 than insulin glargine U-100, thereby reducing an important concern of providers and patients regarding insulin therapy. Although a higher dose of insulin glargine U-300 than U-100 is required in most patients, the observed increase in body weight is small and less than with insulin glargine U-100.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Male; Middle Aged; Treatment Outcome

The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high. However, randomized studies comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once-weekly [OW; DURATION-3 (Diabetes therapy Utilization: Researching changes in A1c, weight, and other factors Through Intervention with exenatide ONce-Weekly)] and liraglutide once-daily [OD; LEAD-5 (Liraglutide Effect and Action in Diabetes)] with insulin glargine documented greater HbA1c reduction with GLP-1RAs, from baseline HbA1c ∼8.3% (67 mmol/mol). This post hoc analysis of DURATION-3 and LEAD-5 examined changes in HbA1c, fasting glucose and weight with exenatide OW or liraglutide and glargine, by baseline HbA1c quartile.. Descriptive statistics were provided for change in HbA1c, fasting glucose, weight, and insulin dose, and subjects (%) achieving HbA1c <7.0%, by baseline HbA1c quartile. Inferential statistical analysis on the effect of baseline HbA1c quartile was performed for change in HbA1c. An analysis of covariance (ANCOVA) model was used to evaluate similarity in change in HbA1c across HbA1c quartiles.. At 26 weeks, in both studies, HbA1c reduction, and proportion of subjects reaching HbA1c <7.0%, were similar or numerically greater with the GLP-1RAs than glargine for all baseline HbA1c quartiles. Fasting glucose reduction was similar or numerically greater with glargine. Weight decreased with both GLP-1RAs across all quartiles; subjects taking glargine gained weight, more at higher baseline HbA1c. Adverse events were uncommon although gastrointestinal events occurred more frequently with GLP-1RAs.. HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c. This suggests that liraglutide and exenatide OW may be appropriate alternatives to basal insulin in type 2 diabetes, including when baseline HbA1c is very high (≥9.0%).

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Fasting; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Metformin; Middle Aged; Peptides; Treatment Outcome; 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

This study investigated the long-acting antidiabetic efficacy of PEGylated fibroblast growth factor (FGF)-21 in type 2 diabetic db/db mice.. PEGylated FGF-21 was prepared by modifying the N-terminus of human FGF-21 (hFGF-21) using mPEG-ALD. To compare the long-lasting hypoglycaemic effects of PEGylated FGF-21 and insulin glargine in diabetic db/db mice, their pharmacological efficacy was evaluated by changes in blood glucose levels, body weight, insulin levels, glycosylated haemoglobin levels, lipid profile and liver function parameters, and by oral glucose tolerance tests (OGTTs).. Both PEGylated FGF-21 and insulin glargine decreased plasma glucose in db/db mice. However, compared with insulin glargine treatment, PEGylated FGF-21 therapy had more significant effects in lowering blood glucose and glycosylated haemoglobin levels, improving lipid profile and liver function parameters, alleviating insulin resistance and reducing the glucose area under the curve in OGTTs.. Our results suggest that PEGylated FGF-21 is an ideal candidate as a long-acting antidiabetes drug, and holds significant promise as an effective therapeutic agent in the treatment of type 2 diabetes patients.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Eating; Fibroblast Growth Factors; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Polyethylene Glycols

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 have previously shown that insulin plays an important role in the nutrient-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical type 2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were treated with glargine once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and cholesterol content in mitochondria in tissues. Cholesterol content in mitochondria and its association with oxidative stress in cultured hepatocytes and β-cells were also examined. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased cholesterol content in mitochondria of liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β-cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce typical T2DM in normal mice fed on a chow diet.

Topics: Animals; Blood Glucose; Body Weight; Cell Line, Tumor; Cells, Cultured; Cholesterol; Cricetinae; Cytokines; Diabetes Mellitus, Type 2; Diet; Fats; Hepatocytes; Hypoglycemic Agents; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Insulinoma; Lipids; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Pancreas; Reverse Transcriptase Polymerase Chain Reaction

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

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

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

This observational study evaluated the clinical effectiveness of exenatide BID (exenatide) vs. insulin glargine (glargine) in patients with type 2 diabetes mellitus in ambulatory clinical practice.. Retrospective analyses were conducted using an electronic medical record (EMR) database among adult patients with type 2 diabetes mellitus initiating exenatide or glargine between 1 November 2006 and 30 April 2009. The cohorts were propensity-score matched to control baseline demographics, clinical measures, health status and medication use. The changes from baseline to a 12-month follow-up period for A1C (primary outcome), weight, body mass index (BMI), blood pressure and lipid levels were compared between the matched cohorts using paired tests.. Propensity-score matching between the exenatide (n = 4494) and glargine (n = 5424) cohorts led to 2683 matched pairs with comparable characteristics, including age, gender and baseline clinical values. The exenatide cohort achieved a greater mean reduction in A1C (-0.6% vs. -0.4%, p < 0.01), weight (-2.6 kg vs. -0.2 kg, p < 0.01), BMI (-0.8 kg/m(2) vs. -0.04 kg/m(2) , p < 0.01) and systolic blood pressure (SBP) (-1.8 mmHg vs. -0.1 mmHg, p < 0.01) in the follow-up period. The changes in diastolic blood pressure and lipid levels were not significantly different between cohorts.. Compared to glargine, exenatide-treated patients experienced significant reductions in A1C, weight, BMI and SBP. Acknowledging the limitations of observational research, exenatide showed greater clinical effectiveness than glargine from a large EMR database in the ambulatory care setting.

Topics: Ambulatory Care; Blood Glucose; Body Mass Index; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Lipids; Male; Middle Aged; Peptides; Retrospective Studies; Treatment Outcome; Venoms; Weight Loss

To determine the clinical usefulness of basal-supported oral therapy (BOT) using insulin glargine in Japanese patients with type 2 diabetes.. We compared HbA1c levels, body weight, and insulin doses before the introduction of BOT and in the final month of the observation period in 122 patients with type 2 diabetes who received BOT with insulin glargine between October 2007 and July 2009. To exclude the possible effects of seasonal changes in glycemic control, 57 of the 122 patients were followed-up for one year and examined for changes in HbA1c levels, body weight, and insulin dose.. Examination of all cases (n=122) showed a significant decrease in HbA1c (before BOT: 8.7±1.8, after: 7.1±1.1%), but no significant change in body weight (before: 63.1±16.1, after: 63.8±17.0 kg). The mean observation period was 10.5±6.4 months. Insulin doses were significantly increased during the study. HbA1c levels improved significantly in patients on non-insulin-secreting drugs (biguanide, α-glucosidase inhibitor and thiazolidine derivatives) than those on insulin-secreting drugs (SU agents and glinides).. BOT with insulin glargine is a useful strategy that can achieve good glycemic control in clinical practice without causing serious hypoglycemia. The introduction of BOT before exhaustion of pancreatic β cells may increase its effectiveness.

Topics: Administration, Oral; Aged; Asian People; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Retrospective Studies; Sulfonylurea Compounds

This study aimed to compare glycemic variations seen among Japanese patients with type 1 diabetes treated with insulin glargine versus insulin detemir using continuous glucose monitoring (CGM) in a crossover design.. Twenty-three patients with type 1 diabetes were enrolled in this study. The subjects were on either insulin glargine followed by insulin detemir twice daily, or vice versa, with no change in the timing of injections. The glycemic variations during 4-day hospitalizations were monitored by CGM while the patients were on either regimen, with a second hospitalization scheduled more than 1 month after the change of the long-acting insulin analogs. CGM data obtained on Day 3 of both hospitalizations were compared.. The subjects had a median age of 44.0 years, a median body mass index of 22.2 kg/m(2), and a median glycosylated hemoglobin of 7.3%. There was no significant difference between the two treatments with a mean glucose level of 156 mg/dL with the insulin glargine treatment versus 150 mg/dL with the insulin detemir treatment; their SD values were 60 versus 51 mg/dL, their mean amplitude of glycemic excursions values were 121 versus 105 mg/dL, and their mean of daily differences values were 45.7 versus 41.4 mg/dL, respectively. In addition, the insulin detemir treatment was associated with a narrower range of postprandial glucose increases after lunch (80 vs. 59 mg/dL; P=0.007).. A comparison of the long-acting insulin analogs administered twice daily in type 1 diabetes demonstrated that insulin detemir may potentially offer better glycemic control after lunch than insulin glargine.

Topics: Adult; Asian People; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

A 7.5-year-old spayed female ferret was evaluated because of weight loss despite a good appetite. Pancreatic insulinoma had been diagnosed at another animal hospital on the basis of detection of low blood glucose concentration on 1 occasion; however, concurrent determination of blood insulin concentration was not performed. The ferret had been treated SC with methylprednisolone acetate (unknown dosage) every 30 days for 2 years. No follow-up data regarding blood glucose concentration were available.. On physical examination, the ferret was thin (weight, 0.619 kg [1.36 lb]) and bruised easily. Serum biochemical analysis revealed hyperglycemia (blood glucose concentration, 855 mg/dL; reference range, 63 to 134 mg/dL).. Glucocorticoid injections were discontinued, and the ferret was administered prednisolone (1.13 mg/kg [0.51 mg/lb], q 12 h for 14 days, then 0.56 mg/kg [0.25 mg/lb], q 12 h for 7 days) orally. After prednisolone administration was discontinued, hyperglycemia and weight loss persisted. The ferret was administered insulin glargine (0.5 U) SC; blood glucose concentration was monitored every 2 hours for 24 hours, at which time the value had decreased to nearly within reference range. The owner continued insulin glargine administration at that dose every 12 hours; after 77 days of treatment, the ferret's weight was 0.731 kg (1.61 lb), which was considered normal, and blood glucose concentration was within reference range.. Regular SC administration of insulin glargine was successful in the treatment of diabetes mellitus in the ferret of this report and may be effective for other diabetic ferrets.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Female; Ferrets; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting

Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Peptides; Pioglitazone; Thiazolidinediones; Venoms

Progressive β-cell dysfunction and loss of β-cell mass are fundamental pathogenic features of type 2 diabetes. To examine if anti-diabetic reagents, such as insulin, pioglitazone (pio), and alogliptin (alo), have protective effects on β-cell mass and function in vivo, we treated obese diabetic db/db mice with these reagents.. Male db/db mice were treated with a chow including pio, alo, or both of them from 8 to 16 weeks of age. Insulin glargine (gla) was daily injected subcutaneously during the same period.. At 16 weeks of age, untreated db/db mice revealed marked increase of HbA1c level, whereas those treated with pio, pio+alo, or insulin revealed the almost same HbA1c levels as non-diabetic db/m mice. Islet mass evaluated by direct counting in the whole pancreas and insulin content in isolated islets were preserved in pio, pio+alo and gla groups compared with untreated or alo groups, and there was no difference among pio, pio+alo and gla groups. To precisely evaluate islet β-cell functions, islet perifusion analysis was performed. In pio, pio+alo and gla groups, biphasic insulin secretion was preserved compared with untreated or alo groups. In particular, pio+alo as well as gla therapy preserved almost normal insulin secretion, although pio therapy improved partially. To examine the mechanism how these reagents exerted beneficial effects on β-cells, we evaluated expression levels of various factors which are potentially important for β-cell functions by real-time RT-PCR and immunohistochemistry. The results showed that expression levels of MafA and GLP-1 receptor were markedly decreased in untreated and alo groups, but not in pio, pio+alo and gla groups.. Combination therapy with pio and alo almost completely normalized β-cell functions in vivo, which was comparable with gla treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Body Weight; Deoxyguanosine; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Insulin, Long-Acting; Maf Transcription Factors, Large; Mice; Mice, Inbred C57BL; Pioglitazone; Piperidines; Receptors, Glucagon; Thiazolidinediones; Triglycerides; Uracil

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 was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands.. Insulin-naïve patients with T2D, starting treatment with IDet or IGlar between January 1, 2004 and June 30, 2008, were selected from the PHARMO data network. Glycemic control (hemoglobin A1c [HbA1c]), target rates (HbA1c <7%), daily insulin dose, and weight gain were analyzed comparing IDet and IGlar for patients with available HbA1c levels both at baseline and at 1-year follow-up. Analysis of all eligible patients (AEP) and a subgroup of patients without treatment changes (WOTC) in the follow-up period were adjusted for patient characteristics, propensity scores, and baseline HbA1c.. A total of 127 IDet users and 292 IGlar users were included in the WOTC analyses. The mean HbA1c dropped from 8.4%-8.6% at baseline to 7.4% after 1 year. Patients at HbA1c goal increased from 9% at baseline to 32% for IDet and 11% to 35% for IGlar, which was not significantly different (OR 0.75, 95% CI 0.46, 1.24). Weight gain (n=90) was less among IDet users (+0.4 kg) than among IGlar users (+1.1 kg), albeit not significant. The AEP analysis (252 IDet + 468 IGlar users) showed similar results with 33%-36% at goal (OR 0.81, 95% CI 0.57, 1.16), and median daily insulin doses of 25 IU/day (P=0.70).. There was no significant difference between users of IDet and IGlar with respect to glycemic control and insulin dose in a real-life setting. The low proportion of patients on target at baseline may indicate that insulin therapy is initiated too late. Moreover, the observation that one-third of the patients reached HbA1c target at follow-up may indicate that basal insulin analogs are not titrated intensively enough.

Topics: Aged; Body Weight; Cohort Studies; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Drug Utilization; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insurance Claim Review; Male; Middle Aged; Retrospective Studies

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 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

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

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

To evaluate long-term effects of treatment with insulin analogue glargine in patients with type 1 diabetes mellitus and to follow up their further course of life.. Retrospective evaluation of 114 patients who, from September 2004, had their basal insulin changed from NPH insulin to insulin glargine. Treatment was changed again in patients in whom a year-long treatment with insulin glargine did not bring improvement in diabetes control. The original sample was divided into 3 groups and the results compared. Compensation of diabetes (HbA1c) after 1, 2 and 3 years and changes to basal and bolus daily insulin dose and body weight were evaluated.. The results are presented as median and 25th and 75th percentile. Group A--75 patients (65%) treated for the entire evaluation period with insulin glargine. Initial HbA1c was 7.3 (6.4-8.2)%, 6.9 (6.0-8.4)% after 1 year, 7.1 (5.9-7.9)% after 2 years and 6.6 (5.5-7.7)% after 3 years (p < 0.001). We did not identify any statistically significant changes to total, basal or bolus daily dose of insulin or statistically significant body weight increase over the evaluation period. Group B--19 patients (17%). Switch from insulin glargine to detemir twice daily. Initial HbA1c was 7.3 (6.9-8.5)%, 7.4 (6.8-8.7)% after 1 year of treatment with insulin glargine, 7.7 (7.2-8.1)% before the treatment switch and 7.8 (6.7-8.5)% (NS) after 3 years of treatment. Daily dose of total, basal and bolus insulin did not change and, similarly, no statistically significant change to patients' bodyweight was identified. Group C--17 patients (15%). Switch from insulin glargine to an insulin pump. This group had better initial compensation with HbA1c 6.7(5.7-8.6)%, HbA1c after 1 year was 6.2 (5.6-8.1)%, 7.0 (6.0-7.4)% before the treatment switch and 6.3 (5.2-7.7)% after 3 years of treatment. Total daily insulin dose: 48 (34-60)-38 (25-49) IU/day (NS). Basal daily insulin dose: 17.5 (13-28) IU/day-23 (12-32) IU/day (NS). Bolus daily dose decreased significantly: from 25.5 (21-33) to 15.5 (12-22) IU/day (p < 0.01). Body weight: 76 (71-97) kg-73 (72-99) kg (NS). Only 3% of patients went back to NPH insulin.. Insulin glargine brings improved control of diabetes. The dose of insulin glargine did not differ from NPH insulin. No statistically significant body weight increase was observed during the evaluation period.

Topics: Adult; Body Weight; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

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

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

Maintaining target glycosylated hemoglobin (HbA(1c)) (<7%) in patients with type 2 diabetes mellitus (T2DM) reduces the risk of late diabetes-associated complications. Previously reported results of a 9-month, uncontrolled, observational study (n = 12,216) showed that the addition of insulin glargine, a basal insulin analog, to existing oral antidiabetic drug (OAD) therapy was associated with reductions in HbA(1c) to target levels. This analysis investigated the effects of long-term, once-daily insulin glargine plus OAD therapy on glycemic control in patients with T2DM in a 32-month extension of the original observational study.. After 9 months of observation, an extension of up to 32 months was offered to the participating physicians. The 32-month data were available for 1,915 patients.. At baseline, mean +/- standard deviation age was 63.5 +/- 11.3 years, HbA(1c) was 8.6 +/- 1.5%, fasting blood glucose (FBG) level was 200.7 +/- 57.8 mg/dL (11.1 +/- 3.2 mmol/L), and body mass index (BMI) was 29.0 +/- 4.8 kg/m(2). Reductions in HbA(1c) (-1.7%) and FBG (-71.4 mg/dL [-4.0 mmol/L]) were observed after 9 months of treatment with insulin glargine plus OADs and were maintained at 32 months (HbA(1c), -1.6%; FBG, -71.8 mg/dL [-4.0 mmol/L]). These improvements were broadly consistent across all BMI categories.. These data suggest that in daily practice the introduction of insulin glargine with continued OAD therapy facilitates both attainment and maintenance of target HbA(1c) levels, irrespective of BMI in patients with T2DM.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Longitudinal Studies; Male; Middle Aged; Treatment Outcome

We wanted to assess the effectiveness and safety of glargine in the treatment of patients with type 2 diabetes mellitus in secondary failure and/or with severe comorbidities ("T2DM group"), and patients with secondary diabetes after corticosteroid and/or anticancer treatment ("secondary DM group"). We reviewed the records of patients on glargine from 1 August 2004 to 30 July 2005. The after-minus-before change in HbA1c was the main outcome measure. At baseline, the 18 "T2DM" patients had a mean (+/-SD) age of 66.7+/-9.5 years and a diabetes duration of 13.6+/-10.3 years; 52.9% were male. Their fasting plasma glucose (FPG) decreased from 228.6+/-76.6 to 134.6+/-37.5, two-hour post-prandial glycaemia (2hPPG) from 268.2+/-10.4 to 140.6+/-30.8 and HbA1c from 10.4+/-2.3 to 7.9+/-1.6%. Mean daily insulin dosage was 12.0+/-4.8 UI for glargine alone and 37.4+/-22.6 UI for basal-bolus scheme. The daily cost was Euro 0.75 (range Euro 0.31-1.15). The 24 "secondary DM" patients had a mean age of 67.0+/-11.0 years and a diabetes duration of 3.7+/-6.5 years; 54.2% were male and 91.7% had a metastatic cancer. Their FPG decreased from 222.3+/-108.6 to 121.5+/-28.7 mg/dl, 2hPPG from 259.4+/-108.6 to 133.0+/-35.0 mg/dl and HbA1c from 10.1+/-2.5 to 7.6+/-1.3%. Mean daily insulin dosage was 12.5+/-6.1 UI for glargine alone and 27.2+/-9.1 UI for basal-bolus scheme. Mean daily cost was Euro 0.70 (range Euro 0.31-1.38). One (4.2%) cancer patient withdrew from glargine because of nausea. Nine (37.5%) cancer patients had an increase in appetite after glargine therapy, including 3 end-of-life patients. No severe hypoglycaemia occurred. Insulin glargine was safe and effective in improving glycaemic control both in severe "T2DM" and in "secondary DM" patients.

Topics: Adrenal Cortex Hormones; Aged; Antineoplastic Agents; Blood Glucose; Body Mass Index; Body Weight; Cardiovascular Diseases; Comorbidity; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Renal Insufficiency; Retrospective Studies; Treatment Outcome

Topics: Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Intravenous; Insulin; Insulin Glargine; Insulin, Long-Acting; Peptides; Venoms

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

Topics: Adult; Body Weight; Delivery, Obstetric; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Insulin Glargine; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics

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: Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Peptides; Prospective Studies; Randomized Controlled Trials as Topic; Venoms

This study compared external insulin pump treatment using insulin lispro or insulin aspart with multiple daily injections (MDI; four or more injections per day) using insulin glargine and insulin lispro or insulin aspart. An electronic database was used to retrieve various parameters of glycemic control for 515 adult patients with type 1 diabetes. An insulin pump was used by 216 patients, and 299 patients were taking insulin glargine for at least 6 months. The mean age (approximately 33 years), duration of diabetes (approximately 16 years), and duration of treatment (approximately 12 months) were similar for both the pump and insulin glargine groups. The mean (+/-SEM) A1C values were significantly reduced in both groups from the baseline to the end of the study (7.7 +/- 0.1% to 7.5 +/- 0.1% for the pump group and 8.0 +/- 0.1% to 7.7 +/- 0.1% for the insulin glargine group, P< 0.001) with similar weight gain (P> 0.05) in both groups. The insulin glargine group significantly reduced basal insulin intake at follow-up. The premeal boluses were similar throughout the study for both groups. The subjects reporting severe hypoglycemic episodes were similar in the two groups; however, there were 12 cases of diabetic ketoacidosis reported in the pump group and none in the insulin glargine group. Patients with type 1 diabetes can achieve similar glycemic control using insulin glargine with premeal insulin lispro or by using an external infusion pump with insulin lispro or insulin aspart. However, costs and episodes of diabetic ketoacidosis are significantly higher for insulin pump users.

Topics: Adult; Body Weight; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusion Pumps, Implantable; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Glargine; Insulin Infusion Systems; Insulin Lispro; Insulin, Long-Acting; Male; Retrospective Studies

To compare hemoglobin A1c (A1C) values at baseline with those after 1 year of insulin glargine therapy and, secondarily, to compare insulin dosage and patients' body weight at baseline and at 1 year.. Retrospective study.. Private endocrinology practice.. One hundred ninety-seven patients with diabetes mellitus who were first prescribed insulin glargine from May 2001-April 2002 and were evaluable after 1 year of therapy. Patients received insulin glargine instead of NPH insulin or in addition to their oral drug therapy. Patients with diabetes type 1 (receiving insulin therapy) or type 2 (receiving oral drug therapy only, a combination of oral drug therapy and insulin, or insulin only) who had been treated with insulin glargine for 1 year were evaluated. Overall, A1C values decreased significantly (p<0.001) by 0.53 +/- 1.4% from a baseline mean of 8.1 +/- 1.7%. In 129 patients with type 2 diabetes previously treated with NPH insulin, A1C decreased significantly (p<0.001) 0.57 +/- 1.5% from baseline. The A1C decreased by 0.71 +/- 1.3% (p=0.0043) from baseline in 33 patients with type 2 diabetes who previously received oral agents only Thirty-five patients with type 1 diabetes demonstrated no significant change in A1C (-0.22 +/- 1.0%, p=0.217) from baseline. In patients receiving insulin at baseline, the number of daily injections increased significantly (p<0.0001) from a median of two at baseline to three at 1 year. Overall, no significant change was noted in total daily insulin requirement or in body weight in any of the patient groups over the 1-year period.. Compared with baseline, insulin glargine therapy at 1 year was associated with an overall significant reduction in A1C of 0.53 +/- 1.4%.

Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Endocrinology; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Obesity; Private Practice; Retrospective Studies