insulin--isophane and Hypoglycemia

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH)-insulin in type 2 diabetes mellitus (T2DM) patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs). Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT) data with exenatide, insulin glargine and placebo as common references.. A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA1c) target and discontinuations due to adverse events (AEs) were treated as binary variables, with risk ratios and odds ratios (ORs) calculated. HbA1c and body weight were treated as continuous variables with difference in mean change from baseline (MD) calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher's method.. Seven RCTs (n=3,301 patients) comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85]) and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96]) favouring lixisenatide over NPH-insulin and comparable changes in HbA1c from baseline (MD = 0.07%; 95% CI = [-0.26%, 0.41%]). In contrast to NPH-insulin, there was a significant reduction in body weight with lixisenatide (MD = -3.62 kg; 95% CI = [-5.86 kg, -1.38 kg]) at study completion. The number of discontinuations due to AEs numerically favoured NPH-insulin over lixisenatide (OR = 2.64; 95% CI = [0.25, 27.96]), with a broad confidence interval.. Lixisenatide treatment was associated with a lower risk of hypoglycaemia and a greater weight loss compared with NPH-insulin. Glycaemic control with lixisenatide treatment was comparable with NPH-insulin. These data suggest that lixisenatide is a beneficial treatment option for T2DM patients with inadequate glycaemic control on OADs, and is associated with reduced risk of hypoglycaemia and weight gain.

Topics: Adult; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Metformin; Peptides; Sulfonylurea Compounds; Treatment Outcome

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

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

The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Randomized Controlled Trials as Topic; Weight Gain

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

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

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

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

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

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

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

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

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

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

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

Basal insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human insulin or long-acting insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human insulin and each long-acting analogue.. Of 285 randomized controlled trials with a duration > 12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov, 20 met eligibility criteria (enrolling 3693 and 2485 in the long-acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed.. Long-acting analogues had a small, but significant effect on HbA1c [-0.07 (-0.13; -0.01)%; p = 0.026], in comparison with NPH human insulin. When analysing the effect of long-acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human insulin [by 0.26 (0.06;0.47) kg/m2; p = 0.012]. Long-acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01].. The switch from NPH to long-acting analogues as basal insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia.

Topics: Adolescent; Adult; Body Mass Index; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Insulin is recommended as a second-line treatment after diet and metformin fail to reach and/or maintain glycemic targets considered to minimize the risk for long-term diabetic complications. Hypoglycemia and the fear of developing hypoglyce-mia, however, remain substantial barriers to the initiation and optimal use of insulin.. The aim of this study was to compare biphasic insulin aspart 30 (BIAsp 30) with biphasic human insulin 30 (BHI 30) with respect to glycemic control and the risk for hypoglycemia using a meta-analysis of clinical trials comparing these insulins in patients with type 2 diabetes mellitus (T2DM).. We included all published and unpublished, randomized, controlled trials in adult patients with T2DM (treatment duration > or = 12 weeks) for which individual patient data were available. All clinical databases and local trial registries of Novo Nordisk A/S (Soeborg, Denmark) were searched to identify clinical trials comparing the 2 products. The predefined primary end point of the study was the overall rate of nocturnal hypoglyce-mia (major, minor, and symptoms-only hypoglycemia occurring from 12:00-6:00 AM). Hypoglycemia was analyzed using a negative binomial distribution model, accounting for exposure time. Glycemic end points were analyzed at 12 to 16 weeks of treatment using ANCOVA, adjusting for baseline. Secondary safety end points were the rates of major hypoglycemia (hypoglycemia requiring third-party assistance), minor hypoglycemia (symptoms confirmed by plasma glucose [PG] <3.1 mmol/L), daytime hypoglycemia (major, minor, and symptoms-only hypoglycemia occurring from 6:01 AM-11:59 PM), overall hypoglycemia (the sum of all major, minor, and symptoms-only episodes), and change in weight from baseline to 12 to 16 weeks of treatment. Secondary efficacy end points were changes in glycosylated hemoglobin (HbA(1c)), fasting PG (FPG), postprandial PG increment (averaged over breakfast, lunch, and dinner), and insulin dose.. Nine randomized, parallel or crossover trials were included (N = 1674; male sex, 57%; mean [SD] age, 61.0 [10.6] years; body mass index, 26.7 [4.6] kg/m(2); HbA(1c), 8.1% [1.4%]; duration of diabetes, 10.9 [7.9] years). Rates of overall hypoglycemia were not significantly different (rate ratio [RR] = 1.08; 95% CI, 0.94-1.24; P = NS) between treatments. BIAsp 30 had a 50% lower rate of nocturnal hypoglycemia than BHI 30 (RR = 0.50; 95% CI, 0.38-0.67; P < 0.01), whereas the rate of daytime hypoglycemia was 24% lower for BHI 30 (RR = 1.24; 95% CI, 1.08-1.43; P < 0.01). The likelihood of major hypo-glycemia was significantly lower with BIAsp 30 compared with BHI 30 (odds ratio = 0.45; 95% CI, 0.22-0.93; P < 0.05). BIAsp 30 was associated with reduced PPG increment (averaged over breakfast, lunch and dinner) compared with BHI 30 (treatment difference, -0.31; 95% CI, -0.49 to -0.07; P < 0.01). There was a significantly larger reduction in FPG associated with BHI 30 (treatment difference, 0.63; 95% CI, 0.31-0.95; P < 0.01). However, no significant treatment difference was found for HbA(1c) (treatment difference, 0.04; 95% CI, -0.02 to 0.10; P = NS).. This meta-analysis found BIAsp 30 to be associated with a significantly lower rate of nocturnal and major hypoglycemia, but a significantly increased risk for daytime hypoglycemia, compared with BHI 30 at a similar level of HbA(1c) in patients with T2DM.

Topics: Adult; Aged; Biphasic Insulins; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Risk; Time Factors

Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire to novel preventive measures of, severe hypoglycaemia. Our studies confirm that severe hypoglycaemia is still a major clinical problem in type 1 diabetes. The individual susceptibility to severe hypoglycaemia is highly varying and conventional risk factors - with major contribution from hypoglycaemia unawareness - only account for a limited part of this variation. Results from a case-series suggest that the use of psychoactive substances may be as significant as alcohol for promotion of risk of severe hypoglycaemia - a finding which needs to be confirmed by case-control studies. We identified elevated renin-angiotensin system activity as a novel predictor of risk of severe hypoglycaemia in type 1 diabetes with potential clinical significance. Thus, three sequential renin-angiotensin system-related risk factors were associated with severe hypoglycaemia, and by including these factors in a common model both subjects at low and at high risk within a one-year period were identified. Preliminary data suggest that this is explained by impaired capability of subjects with high renin-angiotensin system activity to maintain cognitive function during hypoglycaemia. The clinical implications of this finding which, however, must await additional independent confirmation, include prediction and possibly some prevention of severe hypoglycaemia. An evaluation of renin-angiotensin system activity may - together with assessment of other risk factors - contribute to rational individualized setting of glycaemic targets and thereby open for prevention of severe hypoglycaemia. Furthermore, s

Topics: Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Renin-Angiotensin System; Risk Factors

PRESENT (Physicians' Routine Evaluation of Safety & Efficacy of NovoMix 30 Therapy) is a 6-month observational study of safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in 31,044 type 2 diabetes patients from 15 countries. The aim of this article is to describe the study protocol and assess baseline characteristics of patients in various countries according to diabetes duration (<5 years, 5 to or=20 years), to improve treatment decisions in clinical practice. Glycaemic control was similar across all groups: HbA1c 9.3-9.4%; fasting plasma glucose 11.3-11.6 mmol/L; postprandial glucose 15.9-16.3 mmol/L. Major hypoglycaemia was reported by 5% of all patients, minor hypoglycaemia increased with diabetes duration (25.4-30.3%); overall hypoglycaemia rate was 6.7 events/patient/year. Complications increased with diabetes duration; the most reported were hypertension (40.6-71.0%) and hyperlipidaemia (39.4-56.6%). Of patients 38% previously received OADs only, 28% insulin only, 19% insulin with OADs, and 13% received no therapy. Glycaemic control appeared independent of diabetes duration. HbA1c was well above targets and the clinical inertia was quite apparent; even patients with diabetes for <5 years had high HbA1c levels. Patients suffered high rates of complications and hypoglycaemia before starting BIAsp 30 therapy.

Topics: Biphasic Insulins; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Multicenter Studies as Topic; Patient Selection; Research Design

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

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

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

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

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells.

Topics: Adolescent; Child, Preschool; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period; Time Factors; Young Adult

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

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

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

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

To compare the safety and efficacy of insulin detemir with that of neutral protamine Hagedorn (NPH) insulin in older (aged >/=65) and younger (aged 18-64) persons with type 2 diabetes mellitus (DM).. Pooled, post hoc analysis of data from three open-label, randomized studies.. Three multinational Phase III trials.. Four hundred sixteen older and 880 younger persons with DM, treated for 22 to 26 weeks with basal insulin plus mealtime insulin or oral agents.. Hemoglobin A(1c) (HbA(1c)), fasting plasma glucose, glucose variability, hypoglycemic episodes.. Mean treatment difference for HbA(1c) (insulin detemir-NPH insulin) indicated that insulin detemir was not inferior to NPH insulin for both age groups (0.035%, 95% confidence interval (CI)=-0.114-0.183 and 0.100%, 95% CI=-0.017-0.217, for older and younger persons, respectively). Relative risk of all hypoglycemic episodes (insulin detemir/NPH insulin) was 0.59 (95% CI-0.42-0.83) for older persons and 0.75 (95% CI-0.59-0.96) for younger persons. Adverse events were similar between treatments. Fasting plasma glucose was similar between treatments (mean treatment difference 0.97 mg/dL, 95% CI=-8.01-9.95, and 4.69 mg/dL, 95% CI=-2.30-11.67, for older and younger persons, respectively). Mean treatment difference for weight was -1.02 kg (95% CI -1.61 to -0.42) and -1.13 (95% CI -1.58 to -0.69) for older and younger persons, respectively.. Previously reported benefits of insulin detemir, particularly less hypoglycemia and less weight gain, compared with NPH insulin, were the same for older and younger persons with DM at similar levels of HbA(1c).

Topics: Aged; Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

Basal insulin therapy is an integral part of the intensive management of type 1 diabetes and it is also often used in type 2 diabetes. An ideal insulin regimen in patients with diabetes would mirror the 24-h insulin profile of a non-diabetic person, thereby preventing hyperglycaemia without inducing hypoglycaemia. Until recently, available insulins have pharmacokinetic disadvantages, compared to physiological insulin secretion. Insulin detemir is a new basal insulin analogue recently available for commercial use in the UK. Clinical trials have demonstrated lower fasting plasma glucose levels, lower variability in plasma glucose, predictable action profile and a reduced risk of nocturnal hypoglycaemia and weight gain, compared to conventional basal insulins. This study reviews the properties and potential use of insulin detemir.

Topics: Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

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

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

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

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

Biphasic insulin aspart 30 (BIAsp 30 [30% soluble, rapid-acting insulin aspart and 70% protamine-bound insulin aspart], NovoLog Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark), a premixed insulin analogue, addresses both the prandial and basal aspects of glucose regulation when used once or twice daily in patients with type 1 or type 2 diabetes. It provides overall glycemic control similar to biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin) in patients with type 1 or type 2 diabetes.. The aim of this review was to evaluate the safety profile associated with BIAsp 30 in patients with type 1 or type 2 diabetes versus that of comparator insulin products, including BHI 30 and biphasic insulin lispro 25 (Mix 25 [25% biphasic insulin lispro and 75% protaminated lispro], Humalog Mix 75/25, Eli Lilly and Company, Indianapolis, Indiana), together with the basal insulins, including NPH insulin and insulin glargine (Lantus, Sanofi-Aventis Pharmaceuticals, Paris, France).. Data from human clinical studies published in peer-reviewed journals or as conference proceedings that reported safety results in patients with type 1 or type 2 diabetes who were treated with BIAsp 30 versus comparator insulins were evaluated. To locate the appropriate articles, a MEDLINE search was performed for all years up to February 2005, using the following key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin. Additional papers were identified by examining the reference lists in these papers as well as our own personal reference files. Results from 17 publications were analyzed. The analysis included >2600 patients with type 2 diabetes (mean [range] age, 58 [36-70] years; duration of diabetes, 11.8 [9-17] years; and baseline glycosylated hemoglobin [HbA1c], 8.6% [7.5%-9.9%]). It also included 104 patients with type 1 diabetes (mean [range] age, 44.5 [30-58] years; duration of diabetes, 16 [2-30] years; and baseline HbA1c, 8.4% [7.2%-10.4%]).. Hypoglycemia occurred in 43% to 57% of patients receiving BIAsp 30 versus 32% to 57% of patients receiving BHI 30 and 28% of patients receiving NPH insulin. Major hypoglycemic events were uncommon in most studies; but when they did occur, they were reported less frequently in patients receiving BIAsp 30 (2%-8% of patients) than in patients receiving BHI 30 (2%-14% of patients). Furthermore, patients treated with BIAsp 30 were at lower risk of experiencing minor nocturnal hypoglycemia than patients receiving comparator insulin; in 1 study, the relative risk (BIAsp 30 vs BHI 30) was calculated to be 0.63 (95% CI, 0.37 to 1.09). The adverse event (AE) profile, weight gain during treatment, and formation of cross-reactive antibodies were not different between BIAsp 30 and BHI 30. AEs were reported in 36% to 90% of patients receiving BIAsp 30, 38% to 88% of patients receiving BHI 30, and 51% of patients receiving Mix 25. The use of oral antidiabetic drugs in combination with BIAsp 30 did not alter the safety profile of BIAsp 30.. The flexible and convenient treatment regimen offered by BIAsp 30, together with its ability to improve postprandial glucose control, is associated with a safety profile comparable to that of BHI 30 and NPH insulin, with a lower risk of major and nocturnal hypoglycemic events.

Topics: Adult; Aged; Biphasic Insulins; Clinical Trials as Topic; Cross Reactions; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Randomized Controlled Trials as Topic; Weight Gain

It is estimated that 39% of people with diabetes worldwide who use insulin are prescribed premixes, largely because of the practical advantages of addressing both prandial and basal insulin needs with a single product. Rapid-acting premixed insulin analogues such as biphasic insulin aspart 30 (BIAsp 30 [30% soluble insulin aspart and 70% protamine-crystallized insulin aspart], NovoLog Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark) have been developed recently to overcome the pharmacokinetic limitations of regular human insulin used in the most commonly prescribed premix, biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin). It would be expected that these pharmacokinetic improvements would enhance clinical performance. However, the efficacy of BIAsp 30 compared with other common treatment regimens has not yet been systematically reviewed.. The aim of this paper is to review current data on the efficacy of BIAsp 30 in comparison with other treatment strategies in type 2 diabetes, including oral antidiabetic drugs (eg, metformin, sulfonylureas, meglitinides, thiazolidinediones), conventional insulins (eg, BHI 30, NPH insulin), and other analogue insulins (eg, insulin glargine, biphasic insulin lispro 25 [Mix 25, 25% biphasic insulin lispro and 75% protaminated lispro]). The focus will be on comparative efficacy (ie, postprandial glucose [PPG], blood glucose profiles, and glycosylated hemoglobin [HbA1c]).. We identified human clinical studies published through February 2005 involving BIAsp 30 in patients with type 2 diabetes by performing a MEDLINE search (key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin). Additional papers were identified by assessing (1) the reference lists in these studies, (2) published conference proceedings, and (3) our reference files. A total of 21 relevant papers were retrieved: 13 were published as full manuscripts, 1 as a short communication, 5 as abstracts, and 1 as a poster. One paper is currently in press. Novo Nordisk supplied data from an unpublished trial (Study 1536, 2004), as well as data from a trial published in abstract form only (Study 1269, 2002).. A regimen of BIAsp 30 BID, at breakfast and dinner, provides improved PPG control compared with BHI 30 BID, NPH BID, and insulin glargine OD for patients with type 2 diabetes. Fasting plasma glucose (FPG) with BIAsp 30 was not significantly different from FPG with insulin glargine; however, FPG was higher with BIAsp 30 than with NPH. BIAsp 30 prevented excessive PPG excursions whether it was injected at the beginning of a meal or < or =15 minutes after starting a meal. BIAsp 30 was not associated with an increased risk of major hypoglycemia compared with other insulin regimens used in the studies reviewed. The incidence of minor hypoglycemic events with BIAsp 30 varied across studies but occurred with frequency or risk similar to BHI 30, Mix 25, or NPH. Treat-to-target trials reported that BIAsp 30 can be used to intensify insulin therapy and to reach the glycemic target recommended by the American Diabetes Association (ie, HbA1c <7.0%). One study reported a greater lowering of postprandial triglyceride levels with BIAsp 30 than with BHI 30.. BIAsp 30 BID can reduce PPG levels to a greater extent than other common treatment regimens, including basal insulin OD. Using BIAsp 30, even once daily, may allow some patients to reach glycemic targets with a degree of convenience and tolerability that may not be achievable with other treatment regimens.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Complications; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Lipids; Postprandial Period; Randomized Controlled Trials as Topic; Weight Gain

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

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

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

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

A meta-analysis of results from four clinical trials in type 1 diabetes patients showed that insulin detemir (IDet)-based basal/bolus treatment of type 1 diabetes led to improved HbA1c (0.15%-points lower), reduced risk of major hypoglycaemic events (by 2%) and reduction in body mass index (BMI) (0.26 kg/m2) compared to protamine Hagedorn human (NPH) insulin-based basal/bolus therapy in type 1 patients.. A published, validated, peer-reviewed Markov simulation model (the CORE Diabetes Model) projected short-term results obtained from the fixed-effects (weighted average) meta-analysis to long-term incidence of complications, improvements in quality-adjusted life years (QALY), long-term costs and the cost-effectiveness for IDet combinations versus NPH combinations in type 1 diabetes patients. Probabilities of complications and HbA1c-dependent adjustments were derived from the DCCT and other studies. Costs of treating complications in the UK were retrieved from published sources. Total direct costs (complications + treatment costs) for each arm were projected over patient lifetimes from a UK National Heath Service perspective. Both costs and clinical outcomes were discounted at 3.5% annually.. Improved glycaemic control, decreased hypoglycaemic events and BMI with IDet-based basal/bolus therapy led to fewer diabetes-related complications, an increase in quality-adjusted life expectancy of 0.09 years, increased total lifetime costs/patient of 1707 pounds sterling and an incremental cost-effectiveness ratio of 19,285 pounds sterling per QALY gained. Results were stable under a wide range of reasonable assumptions.. Short-term improvements seen with IDet combinations versus NPH combinations led to decreased complications, improvements in QALYs and reductions in complication costs, which partially offset the additional costs of detemir, leading to a cost-effectiveness ratio which fell within a range considered to represent excellent value for money (< 35,000 pounds sterling/QALY gained).

Topics: Adolescent; Adult; Aged; Body Mass Index; Clinical Trials as Topic; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Theoretical; United Kingdom

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

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

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

Tight control can prevent complications in type 2 diabetes, and many patients will require insulin therapy to achieve this. Newer insulin formulations may offer some advantages with regard to patient convenience and a reduction in hypoglycaemia.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Middle Aged; Prospective Studies

Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn.. We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at <20 weeks' gestation).. We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks' gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of <7, lowest glucose level, need for intravenous glucose, respiratory distress syndrome, need for mechanical ventilation or continuous positive airway pressure, neonatal jaundice requiring therapy, brachial plexus injury, and hospital length of stay. The secondary maternal outcomes included hypoglycemic events, hospital admission for glucose control, hypertensive disorder of pregnancy, maternal weight gain, cesarean delivery, and postpartum complications. We used the Bayesian statistics to estimate a sample size of 108 to have >75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890).. There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks' gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61-1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29-1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54-1.16).. In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn.

Topics: Abortion, Spontaneous; Adult; Diabetes Mellitus, Type 2; Female; Fetal Macrosomia; Gestational Age; Humans; Hypoglycemia; Infant, Newborn; Insulin Detemir; Insulin, Isophane; Intensive Care, Neonatal; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pregnancy Outcome; Respiratory Distress Syndrome, Newborn; Shoulder Dystocia

Post-transplantation diabetes mellitus (PTDM) might be preventable.. This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant.. In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24.. At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Intention to Treat Analysis; Kidney Transplantation; Male; Middle Aged; Postoperative Care; Postoperative Period; Risk Factors; Sex Factors; Standard of Care; Time Factors

To observe whether there are sexual-related differences in response to mid- or low-premixed insulin in type 2 diabetic patients.. This was an analysis of CGM data of a previous study. After screening, patients with longstanding T2D receive a 7-day continuous subcutaneous insulin infusion (CSII) therapy, and then subjects were randomly assigned 1 : 1 into two groups receiving Novo Mix 30 or Humalog Mix 50 regimen for a 2-day phage, followed by a 4-day cross-over period. A 4-day continuous glucose monitoring (CGM) was performed during the cross-over period. The primary endpoint was the differences in glycemic control between male and female patients receiving mid- or low-premixed insulin therapy.. A total of 102 patients (52 men and 50 women) completed the study. Our data showed that male patients had significant decrease in mean glucose levels monitored by CGM after three meals during Humalog Mix 50 treatment period compared to those received Novo Mix 30 regimen (0900: 11.0 ± 2.5 vs. 12.2 ± 2.8, 1000: 9.9 ± 2.9 vs. 11.3 ± 3.1, 1200: 8.0 ± 1.9 vs. 9.1 ± 2.5, 1400: 9.2 ± 2.3 vs. 10.3 ± 2.5, and 2000: 7.3 ± 2.1 vs. 8.2 ± 2.4 mmol/L,. Our data indicate that male patients with T2D receiving mid-premixed insulin analogue regimen may have a potential benefit of improvement in glycemic control compared to female patients. This trial is registered with ClinicalTrials.gov ChiCTR-IPR-15007340.

Topics: Aged; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Monitoring, Ambulatory; Sex Factors; Treatment Outcome

A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes.. EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects.. This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits.. www.clinicaltrialsregister.eu no.: 2018-002640-82. Prospectively registered November 20th. 2018. Date of first patient enrolled: June 4th. 2019. This protocol article is based on the EANITATE protocol version 1.3, dated 29. January 2018.

Topics: Benzhydryl Compounds; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Equivalence Trials as Topic; Glucocorticoids; Glucosides; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Monitoring, Physiologic; Multicenter Studies as Topic; Patient Reported Outcome Measures; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

To assess the efficacy and safety of twice-daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self-mixed or basal insulin ± metformin.. We conducted a 26-week, phase III, open-label, treat-to-target, 2:1 randomized trial. Hierarchical testing was used with non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01-5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes.. Non-inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified.. The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

To compare the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) administered three times daily (TID) vs. twice daily (BID), plus metformin, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on basal insulin ± 1 oral antidiabetic drug (OAD).. Randomised, multinational, open-label, treat-to-target trial. Subjects inadequately controlled (HbA1c 7.5-10.0%) on basal insulin and metformin ± 1 OAD were randomised to BIAsp30 TID (n = 220) or BIAsp30 BID (n = 217). Primary endpoint was change from baseline in HbA1c after 24 weeks of treatment.. BIAsp 30 administered either TID or BID with metformin was a safe and effective option when intensifying treatment after failure of basal insulin and OADs in patients with T2DM. Adding a third injection at lunchtime may be preferable if HbA1c remains above target, if the lunchtime meal is the largest meal of the day, or if persistent postprandial hyperglycaemia after lunch is observed.. ClinicalTrials.gov, NCT02582242.

Topics: Administration, Oral; Adolescent; Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; International Agencies; Male; Middle Aged; Treatment Outcome; Young Adult

To confirm non-inferiority of biphasic insulin aspart 30 (BIAsp 30) plus metformin to BIAsp 30 in lowering glycated haemoglobin (HbA1c) in Chinese patients with inadequately controlled type 2 diabetes using oral antidiabetic drugs.. In this 16-week, prospective, randomized, open-label, multicentre, parallel-controlled study, patients aged 18-79 years with HbA1c ≥7% were randomized to BIAsp 30 plus metformin (n = 130) or BIAsp 30 (n = 127). Initially, 500 mg metformin was administered twice daily and BIAsp 30 was administered at 0.2-0.3 U/kg/d. Changes in HbA1c % from baseline to week 16 as well as secondary and safety endpoints were assessed.. In total, 83.66% of patients in the BIAsp 30 plus metformin (n = 110) and the BIAsp 30 (n = 105) groups completed the study. Mean (±standard deviation) change in HbA1c from baseline to endpoint was -1.74 ± 1.64% and -1.32 ± 2.05% with BIAsp 30 plus metformin and BIAsp 30, respectively. Least squares mean treatment difference was -0.67% (95% CI, -1.06; -0.28). The upper limit of the 95% CI was <0.4 (non-inferiority margin). A significantly higher proportion of individuals reached HbA1c <7% with BIAsp 30 plus metformin than with BIAsp 30 (53.15% vs 35.19%; P = 0.0074). At endpoint, daily BIAsp 30 dose (P < 0.001) and weight gain were significantly lower (P < 0.05) in the BIAsp 30 plus metformin group compared with the BIAsp 30 group. No between-group differences in number of hypoglycaemic events were observed.. BIAsp 30 plus metformin was non-inferior to BIAsp 30 in safely reducing HbA1c in this study.

Topics: Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Prospective Studies; Treatment Outcome; Weight Gain

In Japan, premixed insulins are commonly used as starter insulin for type 2 diabetes. This subpopulation analysis assessed the efficacy and safety of twice-daily LM25 (25% insulin lispro/75% insulin lispro protamine) and LM50 (50% insulin lispro/50% insulin lispro protamine) as starter insulin in Japanese subjects, and compared these results with the whole-trial populations of East Asian subjects. In this subpopulation analysis of an open-label, phase 4, randomized trial (CLASSIFY), Japanese subjects received LM25 (n = 88) or LM50 (n = 84) twice-daily for 26 weeks. The primary outcome was change from baseline at Week 26 in glycated hemoglobin (HbA1c). Results for Japanese subjects were generally similar to those for the whole-trial population. Similar changes from baseline in HbA1c were observed for LM25 and LM50 groups (least squares [LS] mean difference [95% confidence interval] of LM25 - LM50 = 0.13 [-0.16, 0.41]%, 1.42 [-1.75, 4.48] mmol/mol, p = 0.388). More LM50-treated subjects than LM25-treated subjects achieved HbA1c targets of <7.0% (59.5% versus 43.2%; p = 0.034) or ≤6.5% (45.2% versus 28.4%; p = 0.027). The reduction in postprandial blood glucose concentrations after morning and evening meals was statistically significantly greater for LM50 than for LM25. The incidence of both hypoglycemia and treatment-emergent adverse events were similar between treatment groups. Both LM25 and LM50 twice daily appear to be effective and well tolerated as starter insulin, although LM50 might be more effective for Japanese type 2 diabetes patients.

Topics: Aged; Asia, Eastern; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Lispro; Insulin Resistance; Insulin, Isophane; Japan; Male; Middle Aged; Postprandial Period

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

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

To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia.. During insulin analogue treatment, the mean nocturnal plasma glucose level was significantly higher than during treatment with human insulin (10.6 vs 8.1 mmol/l). The fasting plasma glucose level was similar between the treatments. Nocturnal hypoglycaemia was registered during 41/101 nights (41%) in the human insulin arm and 19/117 nights (16%) in the insulin analogue arm, corresponding to a hazard ratio of 0.26 (95% CI 0.14 to 0.45; P < 0.0001) with insulin analogue.. Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens as compared to conventional recording of hypoglycaemia.

Topics: Adult; Aged; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin.. In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat-to-target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m(2) ) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self-monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l.. The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed.. Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long-term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin-naïve.

Topics: Aged; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Meals; Middle Aged; Risk; Severity of Illness Index; Solubility

Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night.. This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996).. Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months.. In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Disease Susceptibility; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Male; Middle Aged; Severity of Illness Index

The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM).. It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed.. HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative.. Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes.

Topics: Biphasic Insulins; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Costs; Glycated Hemoglobin; Hypoglycemia; Insulin Aspart; Insulin, Isophane

Basal insulin peglispro (BIL) has a longer duration of action than conventional insulin analogues and a hepato-preferential mechanism of action. This study assessed whether BIL was non-inferior to isophane insulin (NPH) in reducing HbA1c in insulin-naïve patients with type 2 diabetes, when added to pre-study oral anti-hyperglycaemic medications.. This was a Phase 3, open-label, treat-to-target (TTT), randomized trial with a 2-week lead-in, 26-week treatment and a 4-week safety follow-up period. Patients were randomized to bedtime (pm) NPH, morning (am) BIL or pm BIL in a 1:1:1 ratio.. Six hundred and forty-one patients [NPH, n = 213; BIL, n = 428 (am, n = 213; pm, n = 215)] received study drug. BIL was non-inferior to NPH for HbA1c change from baseline at Week 26 with a between-treatment difference (95% confidence interval) of -0.37% (-0.50, -0.23%). HbA1c at baseline was 8.5%, and was lower in BIL- vs NPH-treated patients after 26 weeks of treatment (6.8% vs 7.1%; P < .001). More BIL-treated patients achieved HbA1c <7.0% and HbA1c <7.0% without nocturnal hypoglycaemia. Fasting serum glucose levels and nocturnal hypoglycaemia rates were lower in BIL-treated patients; total hypoglycaemia rates were similar. Treatment-emergent adverse events were similar between groups. Fasting triglycerides decreased from baseline in both groups and to a greater extent with NPH, but were not significantly different between groups at Week 26. Mean alanine aminotransferase (ALT) increased with BIL treatment, but there was no evidence of acute severe hepatotoxicity.. In this TTT study, BIL treatment showed clinically relevant improvements in glycaemic control and a significant reduction in nocturnal hypoglycaemia compared to NPH.

Topics: Aged; Alanine Transaminase; Biguanides; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Polyethylene Glycols; Sulfonylurea Compounds; Thiazolidinediones; Triglycerides

To compare the effectiveness of a free-mix of aspart (A) and detemir (D) insulins (ADIM) with a commonly used premixed fixed-ratio aspart and neutral protamine Hagedorn (NPH) insulin mixture (ANIM) in young children with type 1 diabetes (T1D) treated with twice-daily injections. The trial thus compares not only D vs. NPH, but also flexible, personalized insulin preparations vs. a fixed premixed preparation.. This single-center, open-label, randomized trial included 82 children with T1D. Patients stayed on ANIM for 1 yr of optimization of disease management, then were randomized to either ANIM (N = 41) or ADIM (N = 41) for another year.. Frequency of severe or symptomatic episodes, glycated hemoglobin A1c (HbA1c), and blood glucose (BG) values.. Compared with ANIM, ADIM decreases symptomatic hypoglycemia by approximately 2 fold (p < 0.001) and severe hypoglycemia by 7-10 fold (p = 0.04). ADIM somewhat reduced BG variation. Mean HbA1c was comparable on ADIM (7.9 ± 0.8 %; 63 ± 9 mmol/mol) and ANIM (8.2 ± 0.7 %; 66 ± 8 mmol/mol).. Using a free-mixing preparation of aspart and detemir insulin decreases hypoglycemia in young children with type 1 diabetes.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Male

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

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

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of IDeg and IAsp. This pan-Asian, 26-week trial investigated efficacy and safety of IDegAsp vs biphasic insulin aspart 30 (BIAsp 30) in Asian adults with type 2 diabetes (T2DM), inadequately controlled on once- or twice-daily (BID) basal, premixed or self-mixed insulin.. Participants (mean age 59.8 years, HbA1c 8.4%, FPG 7.9 mmol/L, BMI 25.4 kg/m(2)) were randomised 2:1 to BID IDegAsp (n=282) or BIAsp 30 (n=142) and continued existing metformin treatment. Insulins were administered with breakfast and main evening meal, titrated to a pre-breakfast and pre-main evening meal self-measured plasma glucose target of 4-5 mmol/L.. IDegAsp achieved the primary endpoint of non-inferiority to BIAsp 30 for mean change in HbA₁c (estimated treatment difference [ETD] IDegAsp-BIAsp 30: 0.05% points [95% CI -0.10; 0.20]). IDegAsp was superior in lowering fasting plasma glucose (FPG) (ETD -1.06 mmol/L, 95% CI -1.43; -0.70, p<0.001), and resulted in a lower final mean daily insulin dose (0.79 U/kg vs 0.99 U/kg, estimated rate ratio [RR] 0.79, 95% CI 0.73; 0.85, p<0.0001). Rates of overall confirmed and severe hypoglycaemia were similar between treatments, while rate of nocturnal confirmed hypoglycaemia was numerically (p=ns) lower with IDegAsp. During the maintenance period there was a trend (p=ns) towards lower hypoglycaemia rates for IDegAsp.. In Asian adults with T2DM, IDegAsp BID effectively improves long-term glycaemic control, and compared to BIAsp 30, provides superior reductions in FPG with a lower dose, and numerically less nocturnal hypoglycaemia.

Topics: Adult; Aged; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Treatment Failure

Clinical guidelines recommend point-of-care glucose testing and the use of supplemental doses of rapid-acting insulin before meals and at bedtime for correction of hyperglycemia. The efficacy and safety of this recommendation, however, have not been tested in the hospital setting.. In this open-label, randomized controlled trial, 206 general medicine and surgery patients with type 2 diabetes treated with a basal-bolus regimen were randomized to receive either supplemental insulin (n = 106) at bedtime for blood glucose (BG) >7.8 mmol/L or no supplemental insulin (n = 100) except for BG >19.4 mmol/L. Point-of-care testing was performed before meals, at bedtime, and at 3:00 a.m. The primary outcome was the difference in fasting BG. In addition to the intention-to-treat analysis, an as-treated analysis was performed where the primary outcome was analyzed for only the bedtime BG levels between 7.8 and 19.4 mmol/L.. There were no differences in mean fasting BG for the intention-to-treat (8.8 ± 2.4 vs. 8.6 ± 2.2 mmol/L, P = 0.76) and as-treated (8.9 ± 2.4 vs. 8.8 ± 2.4 mmol/L, P = 0.92) analyses. Only 66% of patients in the supplement and 8% in the no supplement groups received bedtime supplemental insulin. Hypoglycemia (BG <3.9 mmol/L) did not differ between groups for either the intention-to-treat (30% vs. 26%, P = 0.50) or the as-treated (4% vs. 8%, P = 0.37) analysis.. The use of insulin supplements for correction of bedtime hyperglycemia was not associated with an improvement in glycemic control. We conclude that routine use of bedtime insulin supplementation is not indicated for management of inpatients with type 2 diabetes.

Topics: Aged; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Insulin, Short-Acting; Male; Meals; Middle Aged; Sleep

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

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

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

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

To evaluate the effect of liraglutide and NPH on blood glucose fluctuations in patients with newly diagnosed type 2 diabetes mellitus (T2DM).. A total of 63 newly diagnosed T2DM patients were randomized into a liraglutide group and an NPH group. They were treated for 12 weeks. The values of CGM, HbA1C, and BMI were measured and compared before and after treatment.. FPG, HbAlc, and MBG were decreased in both groups after 12 weeks of treatment. In the liraglutide group, the MAGE, SDBG, LAGE, BMI, and waist circumference were significantly 1ower than in the NPH group (p<0.05). Patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects than in the NPH group (p<0.05). The incidence of hypoglycemia episode in the liraglutide group was significantly lower than in the NPH group (p<0.05).. Liraglutide achieved improvements in overall glycemic control similar to NPH in patients with newly diagnosed T2DM. Liraglutide was associated with less glucose fluctuation than NPH treatment as assessed by CGM. In addition, patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects, a lower incidence of hypoglycemia, and some weight reduction.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Liraglutide; Male; Metformin; Middle Aged; Monitoring, Ambulatory; Predictive Value of Tests; Prospective Studies; Time Factors; Treatment Outcome; Waist Circumference

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

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

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

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

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

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

Insulin degludec/insulin aspart (IDegAsp) is the first combination of a basal insulin with an ultralong duration of action, and a rapid-acting insulin in a single injection. This trial compared IDegAsp with biphasic insulin aspart 30 (BIAsp 30) in adults with type 2 diabetes inadequately controlled with once- or twice-daily (OD or BID) pre- or self-mixed insulin with or without oral antidiabetic drugs.. In this 26-week, randomized, open-label, multinational, treat-to-target trial, participants (mean age 58.7 years, duration of diabetes 13 years, BMI 29.3 kg/m(2), and HbA1c 8.4% [68 mmol/mol]) were exposed (1:1) to BID injections of IDegAsp (n = 224) or BIAsp 30 (n = 222), administered with breakfast and the main evening meal and dose titrated to a self-measured premeal plasma glucose (PG) target of 4.0-5.0 mmol/L.. After 26 weeks, mean HbA1c was 7.1% (54 mmol/mol) for both groups, with IDegAsp achieving the prespecified noninferiority margin for mean change in HbA1c (estimated treatment difference [ETD] -0.03% points [95% CI -0.18 to 0.13]). Treatment with IDegAsp was superior in lowering fasting PG (ETD -1.14 mmol/L [95% CI -1.53 to -0.76], P < 0.001) and had a significantly lower final mean daily insulin dose (estimated rate ratio 0.89 [95% CI 0.83-0.96], P = 0.002). Fewer confirmed, nocturnal confirmed, and severe hypoglycemia episodes were reported for IDegAsp compared with BIAsp 30.. IDegAsp BID effectively improves HbA1c and fasting PG levels with fewer hypoglycemia episodes versus BIAsp 30 in patients with uncontrolled type 2 diabetes previously treated with once- or twice-daily pre- or self-mixed insulin.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Meals; Middle Aged; Treatment Outcome

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

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

To assess the cost-effectiveness of insulin detemir compared with Neutral Protamine Hagedorn (NPH) insulin when initiating insulin treatment in people with type 2 diabetes mellitus (T2DM) in Denmark, Finland, Norway, and Sweden.. Efficacy and safety data were derived from a 20-week multi-centre randomized controlled head-to-head clinical trial comparing insulin detemir and NPH insulin in insulin naïve people with T2DM, and short-term (1-year) cost effectiveness analyses were performed. As no significant differences in HbA1c were observed between the two treatment arms, the model was based on significant differences in favour of insulin detemir in frequency of hypoglycaemia (Rate-Ratio = 0.52; CI = 0.44-0.61) and weight gain (Δ = 0.9 kg). Model outcomes were measured in Quality Adjusted Life Years (QALYs) using published utility estimates. Acquisition costs for insulin and direct healthcare costs associated with non-severe hypoglycaemic events were obtained from National Health Service public sources. One-way and probabilistic sensitivity analyses were performed.. Based on lower incidence of non-severe hypoglycaemic events and less weight gain, the QALY gain from initiating treatment with insulin detemir compared with NPH insulin was 0.01 per patient per year. Incremental cost-effectiveness ratios for the individual countries were: Denmark, Danish Kroner 170,852 (€22,933); Finland, €28,349; Norway, Norwegian Kroner 169,789 (€21,768); and Sweden, Swedish Krona 226,622 (€25,097) per QALY gained. Possible limitations of the study are that data on hypoglycaemia and relative weight benefits from a clinical trial were combined with hypoglycaemia incidence data from observational studies. These populations may have slightly different patient characteristics.. The lower risk of non-severe hypoglycaemia and less weight gain associated with using insulin detemir compared with NPH insulin when initiating insulin treatment in insulin naïve patients with type 2 diabetes provide economic benefits in the short-term. Based on cost/QALY threshold values, this represents good value for money in the Nordic countries. Using a short-term modelling approach may be conservative, as reduced frequency of hypoglycaemia and less weight gain may also have positive long-term health-related implications.

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Models, Economic; Quality-Adjusted Life Years; Reproducibility of Results; Scandinavian and Nordic Countries; Weight Gain

Assess safety and glycaemic control in patients initiating insulin with, or switching from basal insulin to, biphasic insulin aspart 30/70 (BIAsp 30) in primary care in Finland.. A non-randomised, non-interventional, open-label, 26-week study of type 2 diabetes (T2D) patients prescribed BIAsp 30 by their physician, who determined starting dose, titration and injection frequency.. 496 patients provided safety data (insulin-naïve n=197; prior insulin n=299 [84.9% received NPH insulin]). Three patients (0.6%) reported four SADRs (three hypoglycaemia, one hypoglycaemia with unconsciousness). HbA1c was significantly (p<0.0001) reduced after 26 weeks' BIAsp 30 therapy (final dose): insulin-naïve -1.4% (44.4 IU); prior insulin -1.1% (77.4 IU). HbA1c<7.0% was achieved by 10% of insulin-naïve patients at baseline and 51% at 26-week follow-up. In the prior insulin group, 7% and 30% of patients had HbA1c<7.0% at baseline and 26 weeks, respectively. Minor hypoglycaemia increased significantly from baseline to study end: insulin-naïve 0.66-6.45 events/patient/year (p<0.0001); prior insulin 5.11-8.58 events/patient/year (p<0.05). Weight increased by 1.0 kg (insulin-naïve) and 1.3 kg (previous insulin).. BIAsp 30, initiated and titrated in T2D patients in primary care in Finland, showed a good safety profile and significantly improved glycaemic control.

Topics: Adult; Aged; Aged, 80 and over; Biphasic Insulins; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Finland; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Primary Health Care; Treatment Outcome

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

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

A randomized, open-label, parallel study was conducted to assess the efficacy and safety of premixed insulin aspart 30 (biphasic insulin aspart [BIAsp] 30) in managing gestational diabetes mellitus (GDM). A total of 323 women with GDM registered at a single center in India were randomly assigned to receive 6 U of either BIAsp 30 (Group A) or premixed human insulin (biphasic human insulin [BHI] 30; Group B) in a 1:1 ratio. Subjects performed home glucose monitoring and visited their care provider twice a month. The primary outcome was the degree of neonatal macrosomia (neonatal birth weight >90th percentile). Groups A and B were demographically comparable at study entry. Before labor onset, Groups A and B achieved similar degrees of fasting plasma glucose and postprandial plasma glucose control (92.97 ± 14.44 vs. 95.43 ± 18.96 and 127.59 ± 28.99 vs. 126.98 ± 29.89, respectively; both p = NS). Neonatal macrosomia frequency was 6.3% in Group A and 6.9% in Group B; however, this difference was not statistically significant. By last visit, the required insulin dose was significantly lower for Group A than Group B (19.83 ± 15.75 IU vs. 26.34 ± 23.15 IU, respectively; p = 0.006). BIAsp 30 was noninferior to BHI 30, producing comparable fetal outcomes when administered during pregnancy. Based on final doses, BIAsp 30 may offer greater treat-to-target potential for pregnant women.

Topics: Biphasic Insulins; Birth Weight; Blood Glucose; Cohort Studies; Diabetes, Gestational; Drug Combinations; Female; Fetal Macrosomia; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; India; Infant, Newborn; Insulin Aspart; Insulin, Isophane; Intention to Treat Analysis; Male; Pregnancy

To determine if self-titration using biphasic insulin aspart 70/30 (BIAsp 30) had a different impact on efficacy and safety across different racial/ethnic subgroups.. This was an exploratory, post hoc analysis by race (White vs. Black/African-American) and ethnicity (Hispanic/Latino vs. non-Hispanic/Latino) of data from the INITIATEplus trial. Participants were treated twice-daily with BIAsp 30 over 24 weeks.. NCT00101751.. Efficacy endpoints included reductions in mean glycated hemoglobin (A1C) and fasting plasma glucose (FPG). Safety endpoints included hypoglycemia rates (events/patient-year) and adverse events. Body weight changes were also measured.. Glycemic control improved by a similar extent for all demographic groups. Observed mean decreases in A1C ranged from 2.4% to 2.6% after 24 weeks' treatment. Baseline-adjusted mean A1C decreases for White vs. Black/African-American subjects were 2.56% and 2.13% (p < 0.0001), and for Hispanic/Latino vs. non-Hispanic/Latino subjects were 2.45% and 2.42% (p = 0.677), respectively. Final FPG values were similar among all groups (141-146 mg/dL [7.83-8.10 m mol/L]), and baseline-adjusted FPG decreases were not significantly different (p > 0.025) between groups. Hypoglycemia was low for White, Black/African-American, Hispanic/Latino, and non-Hispanic/Latino subjects (0.08, 0.04, 0.03, and 0.07 major events/patient-year, with 0.60, 0.30, 0.37, and 0.52 minor events/patient-year, respectively). Body weight increases were 3.17 and 3.06 kg (White vs. African-American) and 2.69 and 3.19 kg (Hispanic/Latino vs. non-Hispanic/Latino). Final weight-adjusted total daily insulin doses were 0.60 U/kg for Black/African-American subjects vs. 0.78 U/kg for White subjects (p < 0.0001), and 0.71 U/kg for Hispanic/Latino subjects vs. 0.74 U/kg for non-Hispanic/Latino subjects (p = 0.42).. The trial was not designed or powered for comparisons across racial or ethnic groups, subjects were not stratified for pre-baseline medication regimens between each race and ethnic group, and unequal subject numbers and baseline A1C disparities existed between the pairs of groups being compared.. Diabetes self-management with BIAsp 30 using an easily followed self-titration algorithm produced low hypoglycemia rates. All subgroups achieved A1C reductions >2.1% and FPG declines >82 mg/dL that were similar across groups, demonstrating that self-titration of BIAsp 30 can successfully be pursued in a primary care setting by patients who had previously failed to meet ADA A1C targets under oral antidiabetes therapy, with race or ethnicity not an obstacle to achieving better glycemic control.

Topics: Biphasic Insulins; Black or African American; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Hispanic or Latino; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; United States; White People

To evaluate the effect of metformin and insulin in glycemic control and compare pregnancy outcome in women with gestational diabetes mellitus (GDM).. This randomized controlled trial was conducted in GDM women with singleton pregnancy and gestational age between 20 and 34 weeks who did not achieve glycemic control on diet were assigned randomly to receive either metformin (n=80) or insulin (n=80). The primary outcomes were maternal glycemic control and birth weight. The secondary outcomes were neonatal and obstetric complications.. Two groups were comparable regarding the maternal characteristics. Two groups were similar in mean FBS (P=0.68) and postprandial measurements (P=0.87) throughout GDM treatment. The neonates of metformin group had less rate of birth weight centile >90 than insulin group (RR: 0.5, 95% CI: 0.3-0.9, P=0.012). Maternal weight gain was reduced in the metformin group (P<0.001). Two groups were comparable according to neonatal and obstetric complications (P>0.05). In metformin group 14% of women needed to supplemental insulin to achieve euglycemia.. Metformin is an effective and safe alternative treatment to insulin for women with GDM. This study does not show significant risk of maternal or neonatal adverse outcome with the use of metformin.

Topics: Adult; Birth Weight; Blood Glucose; Diabetes, Gestational; Drug Therapy, Combination; Female; Fetal Macrosomia; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Lost to Follow-Up; Metformin; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Single-Blind Method; Weight Gain

To explore the safety and effectiveness of treatment with the insulin analogue, biphasic insulin aspart 30 (BIAsp 30), in people with type 2 diabetes mellitus (T2DM) in a subgroup of a Pakistani population from the A1chieve study.. A1chieve was a 24-week, international, prospective, multicentre, open label, observational, non-interventional study designed to evaluate the safety and clinical effectiveness of 66,726 people with T2DM who were initiated with basal insulin detemir, fast actinginsulin aspart, and BIAsp 30 (30% soluble insulin aspart, 70% protamine-crystallized insulin aspart). The study was conducted in 28 countries across Asia, Africa, Latin America, and Europe. Here, we report data from a subgroup of 762 people with T2DM from the Pakistani cohort (insulin naïve and insulin users) who were treated withpremix insulin (BIAsp 30) +/- oral antidiabetic drugs (OADs).. The decrease in HbAlc at week 24 was statistically significant in the entire cohort, the insulin naïve, and insulin users (1.7 +/- 1.1%, 1.8 +/- 1.3% and 1.7 +/- 0.9%, respectively, p<0.001 for all).There was a statistically significant decrease in the mean fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) from baseline toweek 24 in the entire cohort, in the insulin naïve and in the insulin users with BIAsp 30 treatment (p<0.001 for all).No major hypoglycaemic events were reported during the entire study period. There was a statistically significant decrease in the systolic blood pressure (SBP) in all groups (p<0.001). The improvement in the quality of life score (QoL)was statistically significant in all groups (p<0.001 for all).. BIAsp 30 treatment appeared to be well tolerated and effective as indicated byimproved glycaemiccontrol and QoL in people with T2DM in the Pakistani population after 24 weeks.

Topics: Adult; Biological Availability; Biphasic Insulins; Blood Glucose; Blood Pressure; Cholesterol; Diabetes Mellitus, Type 2; Drug Evaluation; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Pakistan; Pharmacovigilance; Prospective Studies; Quality of Life; Treatment Outcome

This A1chieve® study subgroup analysis examined clinical safety and effectiveness of biphasic insulin aspart 30 (BIAsp30) ±OGLDs in 6323 individuals with T2D, switching from biphasic human insulin 30 (BHI30) ±OGLDs.. A1chieve was a 24-week, international, prospective, observational, multi-centre, open-label study in individuals with T2D starting treatment with BIAsp30, insulin detemir or insulin aspart as part of routine clinical care.. Mean baseline (SD) dose BHI was 0.56 (0.25) IU/kg. BIAsp30 was initiated at 0.57 (0.25) U/kg; the daily dose was 0.62 (0.28)U/kg by Week 24. Switching from BHI30 to BIAsp30 was associated with significant mean reduction in HbA1c of 1.7% [-18 mmol/mol] (1.6) from a baseline of 9.1% [76 mmol/mol] (p<0.001); FPG and PPG were also significantly reduced (p<0.001). Major hypoglycaemic episodes decreased from 0.69 events/patient/year at baseline to 0.03 events/patient/year at Week 24. Minor hypoglycaemia decreased from 5.31 to 2.04 events/patient/year from baseline to study-end. Five serious adverse drug reactions (hypoglycaemia) were reported by five individuals (0.1%). Mean bodyweight increased by 0.1 (3.3)kg from baseline to 24 weeks. Improved self-reported quality of life was observed.. Switching from BHI30 to BIAsp30 in individuals with T2D is associated with improvement in glycaemic control and reduced rates of hypoglycaemia, without tolerability or safety issues.

Topics: Adult; Africa, Northern; Aged; Asia; Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; Drug Combinations; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Middle East; Prospective Studies; Quality of Life

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

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

This randomised (1:1), multinational, open-labelled, parallel group trial compared insulin detemir (IDet) with neutral protamine Hagedorn (NPH) insulin, in combination with mealtime insulin aspart, over 1 yr in subjects aged 2-16 yr with type 1 diabetes mellitus. Of 348 randomised subjects, 82 (23.6%) were 2-5 yr (IDet: 42, NPH: 40). This article is a descriptive subgroup analysis of these young children. Baseline characteristics (IDet vs. NPH) were similar: mean age, 4.3 vs. 4.5 yr; diabetes duration, 2.2 vs. 2.1 yr; males, 42.9 vs. 52.5%. Mean haemoglobin A1c (HbA1c) was similar between groups at baseline (8.2 vs. 8.1%), and changed little over 1 yr (8.1 vs. 8.3%). Fasting plasma glucose (FPG) was similar at baseline (8.44 vs. 8.56 mmol/L) and decreased during the study (-1.0 vs. -0.45 mmol/L). A lower rate of hypoglycaemia was observed with IDet compared with NPH (24-h; 50.6 vs. 78.3 episodes per patient-year; nocturnal hypoglycaemia, 8.0 vs. 17.4 episodes per patient-year). No severe hypoglycaemic episodes occurred with IDet, while 3 subjects reported 6 episodes with NPH. Change in weight standard deviation score standardised by age and gender was -0.17 with IDet and +0.03 with NPH. A slightly lower proportion of subjects in this age group reported adverse events with IDet than with NPH (69.0 vs. 77.5%). Serious adverse events were few (5 with IDet, 7 with NPH). In conclusion, long-term treatment with IDet in children aged 2-5 yr suggested similar glycaemic control, greater reduction in FPG, lower rates of hypoglycaemia, no inappropriate weight gain, and fewer adverse events compared with NPH.

Topics: Body Weight; Child, Preschool; Diabetes Mellitus, Type 1; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

To compare insulin Aspart and human insulin with respect to glycaemic control, hypoglycaemic frequency and counter-regulatory responses to spontaneous hypoglycaemia.. Glycaemic control, hypoglycaemic frequency, p-insulin concentrations, insulin dosages and patients' satisfaction were examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed by hospitalization where episodes of spontaneous hypoglycaemia and counter-regulatory hormone responses were evaluated from frequently obtained blood samples.. No difference between soluble insulin and insulin Aspart was found regarding HbA1c (7.0 ± 0.2 vs. 7.0 ± 0.2%, ns), hypoglycaemic frequency (1.1 ± 0.2 vs. 0.9 ± 0.1 events per patient per week, ns), nocturnal hypoglycaemia, severe hypoglycaemic events, dosages of bolus insulin (31.8 ± 0.4 vs. 30.0 ± 0.6 IU day(-1), ns), or NPH insulin (26.7 ± 1.8 vs. 26.0 ± 1.7 IU day(-1) , ns) or in patients satisfaction (ns). Modest differences existed in the counter-regulatory responses regarding growth hormone, glucagon and ghrelin whereas no differences were found in relation to free fatty acid, cortisol, insulin-like growth factor (IGF)-I, IGF-II and IGF-binding proteins 1 and 2. Treatment with insulin Aspart resulted in well-defined peaks in serum insulin concentrations as compared with more blunted insulin peaks using human soluble insulin.. Although insulin Aspart treatment was associated with clear postprandial insulin peaks, no improvement in glycaemic control was obtained and no difference in the hypoglycaemic frequency was observed. However, insulin Aspart elicited a slightly different physiological response to spontaneous hypoglycaemia compared with human insulin.

Topics: Adolescent; Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Fatty Acids, Nonesterified; Female; Ghrelin; Glucagon; Hormones; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Young Adult

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

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

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

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

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

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

Insulin analogues are widely used but few data exist comparing different analogue regimens. We compared two such regimens in type 2 diabetes mellitus (T2DM) uncontrolled by oral antidiabetic agents (OADs) with or without basal insulin.. In a 26-week multinational, multicentre, randomized treat-to-target trial, OADs were discontinued and subjects randomized to analogue basal-bolus therapy (insulin detemir once daily and insulin aspart mealtimes) or biphasic insulin aspart 30 (30% rapid-acting insulin aspart), twice daily. Insulin was titrated to targets for fasting, predinner and postprandial plasma glucose (PG), as appropriate.. Of 719 subjects, 92% completed the study; 58% achieved haemoglobin fraction A(1c) (HbA(1c)) < or =7.0%, with reductions of 1.56% (to 6.96%) with basal-bolus therapy and 1.23% (to 7.17%) with biphasic insulin aspart. Reduction with basal-bolus therapy was superior in the overall population by 0.23% (p = 0.0052), with no difference between regimens in insulin-naive patients. Major hypoglycaemia occurred in five basal-bolus patients (0.9%) and in no patients with biphasic insulin aspart. Incidence of minor hypoglycaemia was similar in both groups. All insulin doses increased during titration, with increase in lunchtime insulin aspart dose and equal distribution of breakfast and dinner biphasic insulin aspart doses. Insulin detemir remained once daily in 87% of patients.. Modern insulin analogue regimens, adjusted to PG targets, enable a majority of people with T2DM to reach HbA(1c)< or =7.0% after failure of OADs and OAD-basal insulin therapy. Insulin-treated patients may benefit more from transfer to analogue basal-bolus therapy, while insulin-naive individuals benefit equally well from the more convenient biphasic analogue regimen.

Topics: Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

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

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

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

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

The IMPROVE observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes in routine practice in 11 countries.. Patients who initiated insulin therapy with, or switched existing insulin therapy to, BIAsp 30 in routine care were eligible for this 26-week, non-interventional observational study. Data on adverse events, hypoglycaemia and glycaemic parameters were obtained from patients' diaries and medical notes. Questionnaire-based patient treatment satisfaction was also measured. We report global results and, uniquely for a diabetes observational study, country-specific data.. A total of 52,419 patients were enrolled from three prestudy treatment groups: no pharmaceutical therapy (n = 8966, diabetes duration 2.0 years, baseline HbA1c 9.9%), oral antidiabetic drugs (OADs) only (n = 33,797, diabetes duration 7.4 years, baseline HbA1c 9.2%) and insulin +/- OADs (n = 9568, diabetes duration 10.4 years, baseline HbA1c 9.3%). At final visit, HbA1c, fasting and postprandial blood glucose were significantly reduced from baseline in all subgroups (no pharmaceutical therapy: -3.1%, -5.9 and -9.0 mmol/l, respectively; OADs-only: -2.1%, -4.1 and -6.1 mmol/l; insulin +/- OADs: -2.0%, -3.3 and -5.1 mmol/l). Major hypoglycaemia rates decreased in all subgroups; minor hypoglycaemia increased in the insulin-naïve groups. There was no mean weight gain across subgroups. Across all countries, glycaemic parameters and major hypoglycaemia were reduced; weight increases were seen in some countries. Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy.. Initiating insulin with, or switching insulin therapy to, BIAsp 30 in routine care resulted in improved glycaemic control, reduced major hypoglycaemia and greater treatment satisfaction.

Topics: Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

IMPROVE is an open-label, multinational, non-randomised, 26-week observational study designed to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in routine clinical practice. Here, we report data for patients switching to BIAsp 30 from human premixed insulin.. Patients (n = 3856) with type 2 diabetes previously receiving human premixed insulin with or without oral antidiabetic drugs were eligible for inclusion. Demographic data, efficacy end-points (HbA(1c), fasting blood glucose and postprandial blood glucose) and safety end-points (serious adverse drug reactions, hypoglycaemia and adverse events) were collected at baseline and final visit. A subgroup analysis of mean dose change was also undertaken.. Switching patients to BIAsp 30 resulted in significant improvements in glycaemic control combined with a reduced risk of hypoglycaemia. Patients who reached the HbA(1c) target (< 7%) had shorter diabetes duration, lower HbA(1c) at baseline and needed less insulin. Over 30% of patients were able to reach this target without experiencing hypoglycaemia over the 26-week period. Compared with asymmetric dose switching, unit-for-unit switching resulted in the highest proportion of patients reaching HbA(1c) target and incurred the least amount of dose titration.. A unit-for-unit switch is the most effective as well as the simplest approach when transferring patients from biphasic human insulin 30 to BIAsp 30.

Topics: Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Risk Factors; Treatment Outcome

The IMPROVE study is an openlabel, nonrandomized, observational study aimed at determining the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) treatment in subjects with type 2 diabetes from 11 countries. Here, we report the baseline data of the Indian cohort.. All subjects with type 2 diabetes requiring insulin and considered suitable for BIAsp 30 therapy based on their physician's clinical judgment were eligible to enter the study. The data recorded at baseline included demographic characteristics, detailed medical histories, physician-cited reasons for starting BIAsp 30 treatment, and the chosen dosage regimens.. The Indian cohort included 17,995 subjects with diabetes. Poor glycemic control (glycated hemoglobin [HbA(1c)], 8.7%-9.6%) was observed at baseline in all four geographical zones (North, South, East, and West) and prestudy treatment groups (no therapy, only oral antidiabetic drug [OAD], OAD +/- insulin, and OAD +/- insulin +/- BIAsp 30). Prevalence of both micro- and macrovascular complications was high, also reflecting poor glycemic control. Improving HbA(1c) and fasting and postprandial blood glucose levels were the most common reasons for starting BIAsp 30 therapy. The subjects were prescribed a mean BIAsp 30 dose of approximately 24 IU, and a twice-daily regimen was employed in almost 80% of subjects.. The baseline results of the IMPROVE study Indian cohort confirm the poor glycemic control and the delayed initiation and/or inadequacy of treatment in subjects with type 2 diabetes. These results also highlight the need for timely and appropriately intensive insulin-based therapy.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Mass Index; Cohort Studies; Demography; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction

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

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

To compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA).. In a controlled multicenter and open-label trial, we randomly assigned patients with DKA to receive intravenous treatment with regular or glulisine insulin until resolution of DKA. After resolution of ketoacidosis, patients treated with intravenous regular insulin were transitioned to subcutaneous NPH and regular insulin twice daily (n = 34). Patients treated with intravenous glulisine insulin were transitioned to subcutaneous glargine once daily and glulisine before meals (n = 34).. There were no differences in the mean duration of treatment or in the amount of insulin infusion until resolution of DKA between intravenous treatment with regular and glulisine insulin. After transition to subcutaneous insulin, there were no differences in mean daily blood glucose levels, but patients treated with NPH and regular insulin had a higher rate of hypoglycemia (blood glucose <70 mg/dl). Fourteen patients (41%) treated with NPH and regular insulin had 26 episodes of hypoglycemia and 5 patients (15%) in the glargine and glulisine group had 8 episodes of hypoglycemia (P = 0.03).. Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin. Thus, a basal bolus regimen with glargine and glulisine is safer and should be preferred over NPH and regular insulin after the resolution of DKA.

Topics: Adult; Blood Glucose; Diabetic Ketoacidosis; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Middle Aged; Patient Compliance; Recombinant Proteins

To evaluate clinical efficacy and safety of biphasic insulin aspart (BIAsp) 30 twice daily (b.i.d.) vs. BIAsp 50 or BIAsp 70 (high-mix regimens) thrice daily (t.i.d.) all in combination with metformin in a 36-week clinical trial in subjects with type 2 diabetes.. Efficacy measurements included haemoglobin A(1c) (HbA(1c)) and eight-point plasma glucose (PG); safety included adverse events (AEs) and hypoglycaemic episodes. The three treatment groups (approximately 200 subjects in each group) were well matched regarding sex ratio, ethnicity, age and body mass index.. After 12 weeks, 43% and 54% in the BIAsp 50 and 70 groups, respectively, switched their dinner insulin to BIAsp 30. Both high-mix regimens were non-inferior to BIAsp 30 b.i.d., as measured by change in HbA(1c), and the BIAsp %50 regimen was superior. The odds for meeting the American Diabetes Association and The American Association of Clinícal Endocrinologist HbA(1c) targets of <7% and < or =6.5%, respectively, were significantly higher with the BIAsp 50 regimen than with BIAsp 30. A significantly lower PG level was achieved from lunch until 02:00 hours with both high-mix regimens compared with BIAsp 30 b.i.d. AEs were mild or moderate with all three regimens. Frequency of hypoglycaemic episodes was comparable for the BIAsp 50 and the BIAsp 30 b.i.d. regimens but was significantly higher with BIAsp 70 t.i.d.. Glycaemic control improved with BIAsp 50 t.i.d. without higher incidence of hypoglycaemia compared with BIAsp 30 b.i.d.; with BIAsp 70 t.i.d. lower PG levels from lunch to 02.00 hours, but more hypoglycaemic episodes were obtained compared with BIAsp 30 b.i.d.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Treatment Outcome

The international IMPROVE observational study investigated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in the routine treatment of patients with type 2 diabetes. We present analyses for the subgroup of patients who switched from basal insulin to BIAsp 30.. Patients in routine care who started insulin therapy with or switched to BIAsp 30 from existing insulin regimens were eligible for this 26-week study. This analysis includes only patients previously treated with basal insulin. Outcomes including adverse events, hypoglycaemic events and glycaemic profile were recorded from patients' notes, recall and diaries.. Of the 748 patients included (age 59.7+/-11.8 years, diabetes duration 11.4+/-7.3 years, baseline HbA1c 9.1+/-1.6%), 497 were previously using human neutral protamine Hagedorn (NPH) insulin and 245 analogue basal insulin. Overall, major and minor hypoglycaemia rates decreased from baseline to final visit (major: 0.171 to 0.011; minor: 9.70 to 5.89 events/patient-year) and were similar between the subgroups. HbA1c and fasting blood glucose were significantly reduced from baseline (NPH prestudy: -1.6%, -2.4 mmol/l; analogue basal prestudy: -1.8%, -2.4 mmol/l), as was postprandial blood glucose, with 33.8% of patients achieving the HbA1c target < 7% without hypoglycaemia. Insulin dose increased slightly from prestudy (0.33+/-0.21 U/kg), baseline (0.40+/-0.20 U/kg) to final visit (0.52+/-0.26 U/kg); most patients (76%) followed a twice-daily regimen at final visit. Body weight did not change significantly and treatment satisfaction increased.. Patients with type 2 diabetes inadequately controlled on basal insulins may improve their glycaemic control by intensification to BIAsp 30 therapy.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

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

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

To compare blood glucose control when using biphasic insulin aspart (BIAsp) three times a day (using 70/30 high-mix before breakfast and lunch), with biphasic human insulin (BHI, 30/70) twice daily in adults with type 2 diabetes already treated with insulin.. In a 60-day, open-label, crossover study, people with insulin-treated type 2 diabetes [n = 38, baseline haemoglobin A1c 8.3 +/- 0.9 (s.d.) %] were randomized to BIAsp three times a day before meals, as BIAsp 70 (70% insulin aspart and 30% protamine-complexed insulin aspart) before breakfast and lunch and BIAsp 30 (30/70 free and protamine-complexed insulin aspart) before dinner, or to human premix insulin (BHI) 30/70 twice a day before meals. A 24-h in-patient plasma glucose profile was performed at the end of each 30-day treatment period. The total daily insulin dose of BIAsp regimen was 110% of BHI and the doses were not changed during the study.. There was no difference between BIAsp and BHI in geometric weighted average serum glucose over 24 h [7.3 vs. 7.7 mmol/l, BIAsp/BHI ratio 0.95 (95% CI 0.88-1.02), not significant (NS)], but daytime geometric weighted average glucose concentration was significantly lower with the BIAsp regimen than with BHI [8.3 vs. 9.2 mmol/l, BIAsp/BHI ratio 0.90 (0.84-0.98), p = 0.014]. The mealtime serum glucose excursion was also lower with BIAsp than with BHI with statistically significant differences at lunchtime [difference -4.9 (-7.0 to -2.7) mmol/l, p = 0.000); the difference in glucose excursions above 7.0 mmol/l was also significant [-5.8 (-8.3 to -3.2) mmol/l, p = 0.000). The proportion of participants experiencing confirmed hypoglycaemic episodes was similar between regimens (42 vs. 43%, NS).. An insulin regimen using high-mix BIAsp (BIAsp 70) before breakfast and lunch and BIAsp 30 before dinner can achieve lower blood glucose levels during the day through reduced mealtime glucose excursions in particular at lunchtime than a twice-daily premix regimen.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; England; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome; Young Adult

We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(epsilon-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake.. After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-(2)H(2)]glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration.. During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir.. In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counter-regulation are similar.. ClinicalTrials.gov NCT00760448.

Topics: Blood Glucose; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Epinephrine; Glucose; Growth Hormone; Heart Rate; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Liver; Patient Selection; Reaction Time

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

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

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

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

To compare the efficacy and safety of insulin aspart (IAsp) and human insulin (HI) when applied as meal-time insulin with neutral protamine Hagedorn insulin (NPH) at bedtime in diabetics.. A total of 220 Chinese subjects with type 1 or type 2 diabetes from 5 different hospitals were randomized by a ratio of 1:1 into two groups accepting IAsp or HI combined with NPH respectively. The main endpoints were assessed by fasting plasma glucose (FPG), 2 hour postprandial plasma glucose (2 h PPG), HbAlc and hypoglycemia.. A greater reduction in mean 2 h PPG was achieved in the IAsp group [(14.6 +/- 5.3) mmol/L] as compared with the HI group [(8.4 +/- 4.1) mmol/L] (P < 0.01, adjusted for baseline value, center effect and diabetes type). Significantly more IAsp-treated subjects reached the 2 h PPG target (50.0% vs 25.5%, P < 0.01). HbA1c was reduced more in IAsp/NPH group [(9.3 +/- 1.4)% vs (7.7 +/- 1.3)%] than in HI/NPH group [(9.2 +/- 1.2)% vs (7.7 +/- 1.2)%]. HbA1c target was reached by 24.5% (IAsp) vs 14.5% (HI) of subjects (P < 0.05). No major hypoglycemia or serious adverse events were observed for the IAsp group. Lower incidence of nocturnal hypoglycemia (IAsp/NPH: 3% vs HI/NPH: 4%) was reported in the IAsp group. Average daily insulin doses were 0.60/0.23 (IAsp/NPH) and 0.65/0.24 (HI/NPH) IU/kg respectively.. Treatment of IAsp in basal-bolus therapy in combination with NPH provides a superior postprandial glucose control and allows more subjects to reach the glycemic target without elevating the nocturnal hypoglycemic risk or adverse events.

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Protamines; Young Adult

To evaluate the efficacy, safety and treatment satisfaction with biphasic insulin aspart 30 (BIAsp30) in elderly patients with type 2 diabetes.. The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 0 Therapy Korea study was a 6-month, prospective, observational study. No study-specific interventions were involved except the collection of data. All patients with type 2 diabetes not adequately controlled on their previous therapy, and who were prescribed BIAsp30 as monotherapy, or in combination with oral hypoglycaemic agents, were eligible for the study. This subgroup analysis was based on the outcomes in patients > or years (n = 1720).. BIAsp30 treatment was associated with significant mean reductions in haemoglobin A1c, fasting plasma glucose and post-prandial plasma glucose levels of 1.2 +/- 1.6%, 2.3 +/- 3.5 mmol/l and 4.8 +/- 5.3 mmol/l at 6 months (p < 0.0001 for all), from baseline levels of 9.1 +/- 1.7%, 10.7 +/- 3.4 mmol/l and 16.7 +/- 5.0 mmol/l, respectively. The rate of hypoglycaemia declined from 3.02 to 1.31 episodes per patient year, between baseline and study end. The proportion of patients reporting adverse drug reactions was low (0.3 and 0.1% at 3 and 6 months, respectively). Body weight gain was mild at <0.1 kg at 3 months, and 0.3 kg at 6 months. As compared to the previous treatment, >80% of patients were rated as being either 'very satisfied' or 'satisfied' with BIAsp30 treatment.. In this subanalysis of Korean elderly patients with type 2 diabetes inadequately controlled on their previous therapies, treatment with BIAsp30 offered improvements in glycaemic control and was well tolerated. Body weight gain was minimal with BIAsp30, and treatment satisfaction among these patients appeared to be high.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Postprandial Period; Prospective Studies; Treatment Outcome

PRESENT (Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy) is the largest, multinational, open-labelled, uncontrolled and completed observational study of the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) treatment in clinical practice. We present results of 3 months of treatment in Chinese patients with type 2 diabetes mellitus who were inadequately controlled on current treatment.. Patients received BIAsp 30 treatment with or without oral antidiabetic drugs (OADs). Patients were categorized according to their treatment prior to entering the study: drug-naive (n = 3697), OAD (n = 4754), insulin (n = 2392) or OAD + insulin (n = 817).. At 3 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-2.24 +/- 1.67, -2.04 +/- 1.57, -1.82 +/- 1.49 and -1.86 +/- 1.61%), fasting plasma glucose (-3.93 +/- 3.12, -3.51 +/- 2.55, -2.99 +/- 2.93 and -3.38 +/- 3.16 mmol/l) and postprandial plasma glucose (-7.09 +/- 4.92, -6.51 +/- 4.02, -5.20 +/- 4.31 and -5.50 +/- 4.32 mmol/l) in the drug-naive, OAD, insulin and insulin + OAD groups respectively (p < 0.001). The proportions of patients in each group achieving target HbA(1c) of less than 7% were higher at 3 months (49.5, 51.8, 51.0 and 48.3%) compared with baseline (3.2, 4.2, 7.1 and 8.3%). The rates of hypoglycaemic episodes (events per patient-year) were lower at the end of the study in all the groups compared with baseline. Hypoglycaemic episodes were mostly minor and diurnal in nature. A total of 151 adverse drug reactions were reported, of which five were serious adverse drug reaction (SADRs). These SADRs were all symptoms of local hypersensitivity.. The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was efficacious and safe in Chinese patients with poorly controlled type 2 diabetes.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Treatment Outcome

Weight gain often occurs when insulin therapy is initiated. The long-acting insulin analog insulin detemir has been shown to be effective and well tolerated when used in basal-bolus regimens or as an add-on to oral antidiabetic drugs (OADs) and causes less weight gain than other insulins. The aim of this exploratory analysis was to investigate any correlations between weight change and occurrence of hypoglycemia with NPH insulin and insulin detemir.. The analysis was based on a 26-week, randomized, multicenter, open-label, parallel-group trial in which glycemic control, hypoglycemia, and weight change were compared between insulin detemir and NPH insulin. A total of 476 insulin-naive patients with type 2 diabetes treated with one or two OADs added insulin detemir (n=237) or NPH insulin (n=239) morning and evening to their current oral treatment. Weight gain data from this study were analyzed as a function of hypoglycemia frequency.. Both groups achieved excellent glycosylated hemoglobin control (insulin detemir, 6.6%; NPH insulin, 6.5% [difference not significant]). Weight gain with insulin detemir was less than half that of NPH insulin (1.2 vs. 2.8 kg, respectively [P<0.001]), and the overall risk of hypoglycemia was 47% lower with insulin detemir (P<0.001). No significant relationship between hypoglycemia and weight gain was seen with insulin detemir (P=0.2), while a statistically significant correlation was found for NPH insulin (P=0.003).. Hypoglycemia is predictive of weight gain with NPH insulin, but the same relationship is not seen with insulin detemir. It is therefore likely that the weight-sparing effect of insulin detemir involves other mechanisms.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Risk; Weight Loss

The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians' treatment decisions.. Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen.. Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target-setting for postprandial glucose levels was variable. A twice-daily regimen was used to start BIAsp 30 therapy for 80% or more of patients.. The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians' choice of BIAsp 30, this was not consistently reflected in the targets set.

Topics: Biphasic Insulins; Blood Glucose; Cohort Studies; Decision Making; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To assess weight change when once-daily insulin detemir (detemir) or neutral protamine Hagedorn insulin (NPH) are used in already overweight Type 2 diabetes patients requiring intensified insulin therapy.. This 26-week randomized, controlled trial included adults with Type 2 diabetes [glycated haemoglobin (HbA(1c)) 7.5-11.0%, body mass index (BMI) 25-40 kg/m(2)] who had received two daily doses of insulin (at least one a premix) for > or = 3 months. Subjects received either detemir (n = 125) or NPH (n = 146) once daily in the evening and insulin aspart at main meals. Concomitant treatment with metformin was allowed. Basal insulin was titrated to a pre-breakfast plasma glucose target of 6.1 mmol/l without unacceptable hypoglycaemia. Insulin aspart was also titrated (target, postprandial glucose < or = 10.0 mmol/l without unacceptable hypoglycaemia).. At 26 weeks, weight had increased significantly less with detemir (0.4 kg) than with NPH (1.9 kg; difference 1.5 kg, P < 0.0001). BMI increase was also less with detemir than with NPH (difference 0.6 kg/m(2), P < 0.0001). HbA(1c) decreased from 8.9 to 7.8% (detemir) and from 8.8 to 7.8% (NPH; not significant for between-treatment difference). Incidence of hypoglycaemia was lower with detemir [relative risks 0.62 (all events) and 0.43 (nocturnal); P < 0.0001 for both].. PREDICTIVE BMI was the first study to examine the effect of once-daily detemir with weight as the primary endpoint in a large population of overweight Type 2 diabetes patients. Use of once-daily detemir for intensification of insulin therapy resulted in less weight gain, less hypoglycaemia and equivalent glycaemic control compared with NPH.

Topics: Administration, Oral; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Overweight; Weight Gain

To assess the efficacy and safety of twice- and thrice-daily biphasic insulin aspart 30 (BIAsp 30) in Chinese subjects with type 2 diabetes inadequately controlled with oral antidiabetes drugs (OADs).. In this 24-week, multicenter, parallel-group, randomized, treat-to-target study, 321 Chinese insulin-naïve subjects with poorly controlled type 2 diabetes (fasting blood glucose >or=7.8 mmol/l and A1C >or=7.5%) were randomized (1:1) to twice- or thrice-daily (BID and TID groups, respectively) BIAsp 30 without OADs. Initial insulin doses were based on fasting blood glucose at randomization. Insulin dose was adjusted with algorithm-controlled titration to achieve premeal blood glucose of 4.4-6.1 mmol/l.. A1C decreased significantly in both groups (BID group -2.48 +/- 0.07%; TID group -2.81 +/- 0.07%). Thrice-daily BIAsp 30 showed superiority in A1C improvement (-0.33% [95% CI -0.53 to -0.13]; P < 0.01) and helped more subjects achieve A1C targets <7% (BID group 51.3% vs. TID group 65.8%; P < 0.01). Thrice-daily BIAsp 30 was more effective in subjects with baseline A1C >or=9% (<7%: BID group 41.5% vs. TID group 58.3%; P < 0.01). There was no significant difference in rates of overall and nocturnal major and minor hypoglycemia per subject year between groups. No significant differences in weight gain (BID group 3.87 +/- 0.28 kg; TID group 4.09 +/- 0.27 kg) and mean daily insulin doses (BID group 0.82 +/- 0.28 units/kg; TID group 0.86 +/- 0.34 units/kg) were observed.. Twice- and thrice-daily BIAsp 30 were effective in Chinese insulin-naïve subjects with poorly controlled type 2 diabetes. Thrice-daily BIAsp 30 offered greater reduction in A1C without increasing risk of hypoglycemia, insulin dose, and weight gain, especially in subjects with A1C >or=9%.

Topics: Administration, Oral; Adolescent; Adult; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Safety

The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study aims to assess the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice.. This was a 6-month, prospective, multinational, multiethnic observational study involving 21 977 patients from 13 countries (India, Iraq, Jordan, Kuwait, Lebanon, Qatar, Romania, Russia, Saudi Arabia, South Africa, South Korea, Turkey and the United Arab Emirates). The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs) from prior treatment with OAD (n = 8583), insulin (n = 5942), OAD + insulin (n = 4673) or diet (i.e. treatment naive) (n = 1707). One thousand and seventy-two patients had incomplete or no information on previous treatment.. At 3 and 6 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-1.33 and -1.81%), fasting plasma glucose (-3.02 and -3.74 mmol/l) and postprandial plasma glucose (-4.76 and -5.82 mmol/l) (p < 0.001). A significantly greater proportion of patients achieved target HbA(1c) of less than 7% at 3 months (15.3%) and 6 months (27.7%) compared with baseline (4.8%) (p < 0.001). Overall, the mean HbA(1c) at 6 months was lowered in patients regardless of prior treatment: -2.15% (OAD), -1.45% (insulin), -1.47% (OAD + insulin) and -2.35% (treatment naive). In the overall cohort, the rate of total hypoglycaemia was reduced from 5.4 events per patient-year at baseline to 2.2 events per patient-year at study end (p < 0.001). Among prior treatment subgroups, the rates of total hypoglycaemia were reduced from 2.5 to 2.1 events per patient-year in the OAD group, from 9.6 to 2.2 events per patient-year in the insulin group and from 7.6 to 2.5 events per patient-year in the OAD + insulin group but were increased from 1.0 to 1.8 events per patient-year in the treatment-naive group (p < 0.001). There were 444 adverse drug reactions (ADRs), including 13 serious ADRs: lipodystrophy (three events), symptoms of generalized hypersensitivity (two events), acute painful neuropathy (one event), worsening of diabetic retinopathy (one event), oedema (one event) and unspecified ADRs (five events).. The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in patients with poorly controlled type 2 diabetes mellitus.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Family Practice; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Treatment Outcome

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

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

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

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

This study compared the effect of insulin detemir on glycaemic control (HbA(1c), fasting plasma glucose and variability thereof) with that of Neutral Protamine Hagedorn human isophane (NPH) insulin, both combined with insulin aspart, in children with Type 1 diabetes mellitus, and compared the safety of these treatments.. In this 26-week, open-label, randomized (2 : 1), parallel-group study, 347 (140 prepubertal and 207 pubertal) children with Type 1 diabetes, aged 6-17 years, received insulin detemir (n = 232) or NPH insulin (n = 115) once or twice daily, according to the prestudy regimen, plus premeal insulin aspart.. The mean HbA(1c) decreased by approximately 0.8% with both treatments. After 26 weeks, the mean difference in HbA(1c) was 0.1% (95% confidence interval -0.1, 0.3) (insulin detemir 8.0%, NPH insulin 7.9%). Within-subject variation in self-measured fasting plasma glucose was significantly lower with insulin detemir than with NPH insulin (SD 3.3 vs. 4.3, P < 0.001), as was mean fasting plasma glucose (8.4 vs. 9.6 mmol/l, P = 0.022). The risk of nocturnal hypoglycaemia (22.00-07.00 h) was 26% lower with insulin detemir (P = 0.041) and the risk of 24-h hypoglycaemia was similar with the two treatments (P = 0.351). The mean body mass index (BMI) Z-score was lower with insulin detemir (P < 0.001).. Basal-bolus treatment with insulin detemir or NPH insulin and premeal insulin aspart in children and adolescents with Type 1 diabetes mellitus improved HbA(1c) to a similar degree. The lower and more predictable fasting plasma glucose, lower risk of nocturnal hypoglycaemia and lower BMI observed with insulin detemir are clinically significant advantages compared with NPH insulin.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Risk Factors

Rapid-acting insulin analogs in basal-bolus regimens can reduce nocturnal hypoglycemia, so it is conceivable that twice-daily biphasic insulin analogs might reduce hypoglycemia in patients with insulin-treated type 2 diabetes. We used a continuous glucose monitoring system (CGMS) and self-reported episodes to investigate differences in the frequency of low glucose values in patients with type 2 diabetes, using either biphasic insulin aspart 30 (BIAsp 30) or biphasic human insulin 30 (BHI 30).. This was a double-blind, two-period, crossover trial involving 160 subjects. After 8 weeks' run-in, subjects were randomized to the first of two 16-week treatment periods.. No differences in overall incidence of low interstitial glucose (IG) were found. Twenty-four-hour plots of CGMS showed low IG was more frequent at night than during the day and was unrecognized by patients. At night, subjects spent significantly less time (percentage of total CGMS recorded) with IG <3.5 and <2.5 mmol/l during BIAsp 30 than during BHI 30 treatment, respectively (<3.5 mmol/l: 6.36 vs. 7.93% [mean], 0.67 vs. 2.43% [median], P = 0.018; <2.5 mmol/l: 2.35 vs. 2.86% [mean], 0 vs. 0% [median], P = 0.0467). No treatment difference in A1C was observed.. Overall rates of low glucose over 24 h were not different but were twice as frequent at night than during the day in individuals with type 2 diabetes. Compared with BHI 30, BIAsp 30 was associated with similar low IG readings over 24 h but with fewer nocturnal episodes and less self-reported nocturnal hypoglycemia.

Topics: Aged; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Monitoring, Ambulatory; Self Care

To assess the safety and efficacy of insulin aspart (IAsp) versus regular human insulin (HI) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes.. Subjects (n = 322) who were pregnant or planning pregnancy were randomized to IAsp or HI as meal-time insulin in an open-label, parallel-group, multicenter study. Subjects had A1C < or =8% at confirmation of pregnancy. Insulin doses were titrated toward predefined glucose targets and A1C <6.5%. Outcomes assessed included risk of major maternal hypoglycemia, A1C, plasma glucose profiles, and maternal safety outcomes.. Major hypoglycemia occurred at a rate of 1.4 vs. 2.1 episodes/year exposure with IAsp and HI, respectively (relative risk 0.720 [95% CI 0.36-1.46]). Risk of major/major nocturnal hypoglycemia was 52% (RR 0.48 [0.20-1.143]; P = NS) lower with IAsp compared with HI. A1C was comparable with human insulin in second (IAsp-HI -0.04 [-0.18 to 0.11]) and third (-0.08 [-0.23 to 0.06]) trimesters. A total of 80% of subjects achieved an A1C < or =6.5%. At the end of first and third trimesters, average postprandial plasma glucose increments were significantly lower with IAsp than HI (P = 0.003 and P = 0.044, respectively), as were mean plasma glucose levels 90 min after breakfast (P = 0.044 and P = 0.001, respectively). Maternal safety profiles and pregnancy outcomes were similar between treatments.. IAsp is at least as safe and effective as HI when used in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postprandial glucose control and preventing severe hypoglycemia.

Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 1; Drug Administration Schedule; Europe; Female; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Quality of Life

To compare combination use of repaglinide, metformin and bedtime Neutral Protamine Hagedorn (NPH) insulin with conventional approaches of insulin initiation in patients with Type 2 diabetes (T2DM).. Eighty-two patients with T2DM with suboptimal glycaemic control on oral glucose-lowering agents were randomized to one of three treatment regimens for 4 months. Group 1 received metformin and twice daily biphasic 30/70 human insulin mixture (n = 27), group 2 metformin and bedtime NPH insulin (n = 26) and group 3 metformin, bedtime NPH insulin and mealtime repaglinide (n = 25).. Seventy-five patients completed the study. Baseline and end-point mean HbA1c levels fell from 9.0 +/- 1.1 to 7.9 +/- 1.1% in group 1, 10.0 +/- 2.2 to 9.2 +/- 1.4% group 2 and 10.0 +/- 1.7 to 8.1 +/- 1.5% in group 3, respectively. All groups showed improvements in HbA1c. There was no significant difference between groups in the proportions of patients experiencing hypoglycaemia (29.6, 25.0 and 16.7%, respectively; P = 0.55) or in mean weight gain (2.9, 0.7 and 2.2 kg, respectively; P = 0.06). By 4 months, insulin doses were 0.63 +/- 0.32 IU/kg in group 1, 0.58 +/- 0.21 IU/kg in group 2 and 0.37 +/- 0.22 IU/kg in group 3 (group 3 vs. groups 1 and 2: P < 0.002).. The approach using repaglinide, metformin and NPH insulin improved glycaemic control with a similar safety profile to conventional insulin initiation in T2DM and produced final glycaemic control similar to metformin and a twice daily biphasic insulin mixture.

Topics: Adult; Aged; Aged, 80 and over; Carbamates; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Piperidines; Treatment Outcome; Weight Gain

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

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

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

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

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

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

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

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

Modern premixed insulins offer a flexible approach to the initiation of insulin therapy in patients with poorly controlled type 2 diabetes. A disadvantage of twice-daily regimens of biphasic insulin aspart 30 (BIAsp 30) is that lunchtime control (when no insulin is administered) can be suboptimal. Therefore, it is possible that administering BIAsp 30 thrice daily might further optimize glycemic control and offer an option for patients in whom metformin (MET) is contraindicated.. This study evaluated the efficacy and safety profiles of 2 different regimens of BIAsp 30 compared with a regimen consisting of oral antidiabetic drugs (OADs) alone.. In this multicenter, randomized, open-label, parallel-group trial, insulin-naive patients with poorly controlled type 2 diabetes (baseline glycosylated hemoglobin [HbA(1c) > or =8.0%) who were taking OADs (a sulfonylurea or meglitinide with/without MET or MET only) were randomized to receive BIAsp 30 TID, BIAsp 30 BID + MET, or continuation of their current OAD therapy for 16 weeks. The primary end point was HbA(1c) at the end of the study. Secondary end points included reductions in HbA(1c), mean blood glucose (BG), prandial increment, mean 7-point self-monitored BG profile, weight changes, tolerability (hypoglycemia, adverse events), and satisfaction/quality of life (derived from 2 questionnaires completed at weeks 0, 8, and 16).. The study enrolled 308 insulin-naive patients with type 2 diabetes (78.9% female; mean age, 58.3 years; body mass index, 29.4 kg/m(2); HbA(1c), 10.3%). Both BIAsp 30 TID and BIAsp 30 BID + MET were associated with significantly greater mean (SD) reductions in HbA(1c) relative to OADs alone (absolute percent reduction: 2.9% [1.5%], 3.0% [1.6%], and 2.1% [1.4%], respectively; P < 0.001, both insulin groups vs OAD group) and improved post-prandial glucose control (reduction in mean post-prandial glucose:-6.32 [4.07], -6.44 [4.70], and -3.59 [4.22] mmol/L; P < 0.001, both insulin groups vs OAD group). The mean decrease in the prandial increment was -1.26 mmol/L for BIAsp 30 TID, -2.15 mmol/L for BIAsp 30 BID + MET, and -0.44 mmol/L for OAD. The differences in reduction in the prandial increment were statistically significant for BIAsp 30 TID versus OAD (P = 0.047), BIAsp 30 BID + MET versus OAD (P < 0.001), and BIAsp 30 TID versus BIAsp 30 BID + MET (P = 0.042). Mean body weight increased significantly from baseline with both BIAsp 30 TID and BIAsp 30 BID + MET (+1.71 and +1.50 kg, respectively; both, P < 0.001), and decreased significantly in the OAD group (-0.75 kg; P = 0.003). There were no major hypoglycemic events, and most hypoglycemic events were recorded as symptoms only (144/158 [91.1%]). There were no significant differences in the mean frequency of overall hypoglycemic episodes between BIAsp 30 TID and BIAsp 30 BID + MET (0.73 and 0.69 episodes per patient-year, respectively).. In these patients with type 2 diabetes that was poorly controlled by OADs, BIAsp 30 TID and BIAsp 30 BID plus MET were associated with significantly greater reductions in HbA(1c) and postprandial BG compared with OADs alone. The insulin regimens were associated with significantly more weight gain than OADs alone. There were no differences in rates of hypoglycemia between the insulin regimens.

Topics: Biomarkers; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Quality of Life; Russia; Weight Gain

Insulin aspart has been shown, in medium-term studies, to achieve reductions in HbA(1c) without increasing the risk of major hypoglycaemia compared with pre-meal human insulin. The aim of the present 3-year study was to evaluate the long-term safety and efficacy of insulin aspart in people with type 1 diabetes. This was a 30-month extension of a multinational, multicentre, open-label, parallel-group study of 753 people with type 1 diabetes, originally randomly allocated to treatment with insulin aspart or unmodified human insulin before meals, with NPH insulin as basal insulin. Main outcomes measures were hypoglycaemia (major or minor), adverse events and HbA(1c). As insulin aspart became commercially available in some countries before the end of the trial, analyses of HbA(1c) used 30-month data to maintain statistical power. The relative risk estimate of major hypoglycaemia was similar between treatment groups (relative risk [RR] 1.00 [95% CI 0.72, 1.39]). The risk of having a minor hypoglycaemic episode was higher with insulin aspart than with human soluble insulin (RR 1.24 [1.09, 1.39] p=0.024). Insulin aspart was significantly superior to human insulin with respect to overall glycaemic control, with a baseline-adjusted HbA(1c) difference of -0.16 (-0.32, -0.01)% (p=0.035). Insulin aspart was well tolerated and effective during long-term treatment. The HbA(1c) advantage was maintained with insulin aspart without any adverse impact on the rate of major hypoglycaemia.

Topics: Adult; Body Mass Index; Dose-Response Relationship, Drug; Drug Administration Schedule; Eating; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

This study compared glycaemic control achieved with biphasic insulin aspart 30 (BIAsp 30) monotherapy, BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin.. In this multinational, open-labelled, parallel group, 16-week trial, 341 patients (patients not adequately controlled with metformin for at least 1 month) with type 2 diabetes were studied. Patients were randomized to receive BIAsp 30, twice daily (n = 107 exposed to treatment), or BIAsp 30, twice daily, plus metformin (n = 108) or glibenclamide plus metformin (n = 114). The primary endpoint was HbA(1c) at end of trial; adverse events, hypoglycaemia episodes, blood lipids and weight were also monitored.. In the total population (HbA(1c) 7.5-13.0% at screening), end-of-trial HbA(1c) levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [mean treatment difference (+/-s.e.m), 0.39 +/- 0.15%, p = 0.007]. In a subpopulation (HbA(1c) > or = 9.0% at baseline, n = 193), patients receiving BIAsp 30 plus metformin had significantly lower HbA(1c) levels at the end of the trial compared with those receiving glibenclamide plus metformin (treatment difference, 0.46 +/- 0.21%, p = 0.027). Mean body weight (+/-s.d) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only (84.3 +/- 13.3 kg vs. 88.9 +/- 16.9 kg, p < 0.001). No major hypoglycaemic episodes were recorded during the trial, and incidence rates for minor and symptoms-only hypoglycaemia were low and similar between treatment groups (0.03-0.04 events/patient/week).. BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control, compared with the addition of a second oral agent, particularly where HbA(1c) > or = 9%.

Topics: Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Treatment Outcome

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

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

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

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

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

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

Hypoglycaemia remains a major barrier preventing optimal glycaemic control in Type 1 diabetes due to the limitations of conventional insulin preparations. We investigated whether basal-bolus therapy with insulin detemir (detemir), a new soluble basal insulin analogue, was more effective in reducing the risk of hypoglycaemia compared with NPH insulin (NPH).. In this multinational, open-label, cross-over trial, 130 individuals with Type 1 diabetes received detemir and NPH twice daily in a randomized order in combination with premeal insulin aspart (IAsp) during two 16-week treatment periods. Risk of hypoglycaemia was based on self-measured plasma glucose (SMPG) and self-reported episodes during the last 10 weeks of each period.. Risk of nocturnal and overall hypoglycaemia was, respectively, 50% and 18% lower with detemir than with NPH (P < 0.001). A total of 19 severe hypoglycaemic episodes occurred during treatment with detemir compared with 33 with NPH (NS). HbA(1c) decreased by 0.3% point with both treatments and was comparable at 7.6% (+/- sem 0.06%, 95% confidence interval -0.106, 0.108) after 16 weeks with similar doses of basal insulin. Within-person variation in mean plasma glucose was lower with detemir than with NPH (sd 3.00 vs. 3.33, P < 0.001), as was prebreakfast SMPG (P < 0.0001).. Detemir was associated with a significantly lower risk of hypoglycaemia compared with NPH at similar HbA1c when used in combination with mealtime IAsp. The more consistent plasma glucose levels observed with detemir may allow people to aim for tighter glycaemic control without an increased risk of hypoglycaemia.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

The aim of this study was to compare the effect of multiple mealtime injections of biphasic insulin aspart 30 (30% fast-acting insulin aspart in the formulation, BIAsp30) to traditional basal-bolus human insulin regimen (HI) on glycaemic control in patients with type 1 diabetes.. Twenty-three patients (eight women and 15 men) aged 44.8 (20.6-62.5) years (median and range) with a diabetes duration of 19.5 (1.6-44.6) years completed the study. All eligible patients were randomly assigned to BIAsp30 thrice daily supplied with bedtime NPH insulin when necessary, or basal-bolus HI for 12 weeks and then switched to the alternative regimen for another 12 weeks. The insulin dose adjustments were made by patients on the basis of advice from a diabetes nurse. At end of each treatment period, the patients attended two profile days, 1 week apart for pharmacodynamic and pharmacokinetic assessments. HbA1C was measured at baseline and at the end of each treatment period. A seven-point self-monitored blood glucose (SMBG) was obtained twice weekly.. In comparison with HI, multiple mealtime injections of BIAsp30 resulted in a significant reduction in HbA1C[HI vs. BIAsp30 (%, geometric mean and range): 8.6 (7.4-11.4) vs. 8.3 (6.7-9.8), p = 0.013]. During treatment with BIAsp30, nighttime glycaemic control was significantly improved. Day-to-day variation in pharmacodynamics and pharmacokinetics and the rate of hypoglycaemia were not increased with BIAsp30 compared with HI.. In type 1 diabetics, multiple mealtime administration of BIAsp30 compared with traditional basal-bolus human insulin treatment significantly improves long-term glycaemic control without increasing the risk of hypoglycaemia. Despite a higher proportion of intermediate-acting insulin, thrice-daily injections with BIAsp30 do not increase the day-to-day variations in insulin pharmacokinetics and pharmacodynamics.

Topics: Adult; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

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

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

To show that a thrice daily meal-time biphasic insulin aspart (BIAsp) treatment regimen is as efficacious as a 4 times daily basal-bolus regimen with human isophane insulin (NPH) and insulin aspart (IAsp).. A multinational, randomised, open-label parallel-group trial in 394 patients with type 2 diabetes on a once or twice daily insulin regimen. Patients were randomised 1:1 to BIAsp or IAsp+NPH for 16 weeks. The BIAsp group was treated according to individual needs using BMI as a surrogate index of insulin resistance. Subjects administered BIAsp 70 (BMI< or =30 kg/m (2)) or BIAsp 50 (BMI>30 kg/m (2)) with breakfast and lunch and BIAsp 30 with dinner. The IAsp+NPH group injected IAsp at meals and NPH at bedtime as basal insulin. HbAlc levels after 16 weeks were compared between treatments using a predefined non-inferiority criterion of 0.4%. The incidence of hypoglycaemic episodes and adverse events was evaluated.. Mean HbAlc (+/-SD) decreased from 9.1+/-0.7% to 7.8+/-1.0% with both treatments. Glycaemic control provided by BIAsp was non-inferior to that obtained by the IAsp+NPH (intention to treat ITT) population: diff, HbAlc -0.05%; 95% CI (-0.24; 0.14); per protocol (PP) population: diff, HbAlc -0.03%; 95% CI (-0.23; 0.16). Similar improvements in glycaemic control in both groups were confirmed by self-measured 8-point plasma glucose (PG) profiles, average and fasting PG concentrations, and average prandial PG increments. The incidence of adverse events and hypoglycaemic episodes was similar in the two treatment groups.. A thrice daily meal-time BIAsp regimen is a suitable alternative to an intensified insulin regimen in people with inadequately controlled type 2 diabetes mellitus, and requires fewer daily injections than a basal-bolus therapy without compromising efficacy and safety.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

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

This trial investigated the efficacy and safety of two different administration-time regimens with insulin detemir (IDet) to that of a conventional basal insulin regimen with NPH insulin (NPH).. This multinational, 16-week, open, parallel group trial included 400 people with Type 1 diabetes mellitus (DM) randomized to IDet either morning and before dinner (IDetmorn+din) or morning and bedtime (IDetmorn+bed), or to NPH morning and bedtime (NPHmorn+bed), all in combination with mealtime insulin aspart (IAsp).. HbA1c was comparable between the three groups after 16 weeks (P = 0.64), with reductions of 0.39-0.49% points. Lower fasting plasma glucose (FPG) was observed with IDetmorn+din and IDetmorn+bed compared with NPHmorn+bed (9.8 and 9.1 vs. 11.1 mmol/l, P = 0.006), whereas the IDet groups did not differ (P = 0.15). Within-person variation in self-measured FPG was significantly lower for both IDet regimens (sd IDetmorn+din 2.5, IDetmorn+bed 2.6 mmol/l) than for NPHmorn+bed (sd 3.1 mmol/l, P < 0.001), but was comparable between the IDet groups (P = 0.48). Ten-point plasma glucose profiles were lower between dinner and breakfast in the IDetmorn+din group (P = 0.043), compared with the two other groups. Risk of overall and nocturnal hypoglycaemia was similar for the three groups. Lower mean bodyweight was observed with IDet compared with NPH after 16 weeks (difference: (IDetmorn+din)-1.3 kg, P < 0.001, (IDetmorn+bed)-0.6 kg, P = 0.050).. Both IDet regimens were well tolerated and provided lower and less variable glucose levels with no, or less, weight gain than NPH at comparable HbA1c. IDet can be administered either at dinner or bedtime, with similar glycaemic control according to the need of the individual person.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome; Weight Loss

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

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

Postprandial hyperglycemia contributes to glycation of hemoglobin A1c and has been associated with cardiovascular risk in people with diabetes. We investigated the impact of injection timing of Humalog Mix25 (Mix25, known as Humalog Mix75/25 in the U.S.: 25% insulin lispro and 75% neutral protamine lispro) on glycemia and postprandial blood glucose (BG) excursions in elderly individuals. Seventy-three patients aged 60 to 80 years were randomized to Mix25 (Mix25 group, 37 participants) or a continuation with maximum dose glibenclamide (control group, 36 participants). The Mix25 group was subdivided into a group of 18 patients who were injecting insulin after meals and 19 who were injecting before.. At baseline, the absolute postprandial BG concentrations and postprandial BG excursions after breakfast were high (Mix25 group: 15.3+/-4.8 mmol/l and 3.5+/-2.7 mmol/l, respectively; controls: 15.4+/-3.9 mmol/l and 4.7+/-2.7 mmol/l, respectively). In both groups improvement was observed at the endpoint, but it was greater with Mix25 (Mix25 group: 10.3+/-3.6 mmol/l, p<0.0001 vs. baseline, p<0.003 vs. controls, and 2.0+/-2.5 mmol/l, p<0.008 vs. baseline, p=ns vs. controls; control group: 13.3+/-2.9 mmol/l, p<0.006 vs. baseline, and 4.7+/-2.7 mmol/l, p<0.006 vs. baseline). The two Mix25 subgroups had similar postprandial BG levels and BG excursions after breakfast.. Mix25 improves postprandial BG and yields a greater effect on BG excursions compared with monotherapy with glibenclamide. The timing of Mix25 did not impact the level of BG or BG fluctuations after meals, which may be important for individuals with changing dietary pattern.

Topics: Aged; Aged, 80 and over; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period

Injection of insulin lispro (LP) before meals provides a more physiologic insulin activity profile than regular human insulin, but the relatively short duration of action of LP may allow the blood glucose (BG) level to increase during the late postprandial period (4-7 hours after meals) unless basal insulin is optimally replaced. One approach to basal insulin optimization has been to combine small doses of NPH with LP before meals. When used in a similar fashion, premixed, fixed-ratio insulin preparations containing LP and NPL (an LP-based intermediate-acting insulin) may provide the basis for an optimized basal-bolus insulin regimen.. This study assessed mean late postprandial glycemic control during treatment with a premixed formulation consisting of a high proportion of LP (75% LP/25% NPL; H) and a premixed formulation consisting of a medium proportion of LP (50% LP/50% NPL; M). The H/M formulation was given before meals and was compared with treatment with preprandial LP + NPH (LP + N) in patients with type 1 diabetes mellitus (DM).. This multicenter, randomized, open-label, 2-period crossover study was conducted at 4 centers in Italy and 1 center in France. Patients eligible for the study had type 1 DM, were > or = 18 years of age, and had a glycosylated hemoglobin (HbA(1c)) <150% of the upper limit of normal. Patients were randomly assigned to 1 of 2 treatment sequences: LP self-mixed with NPH before meals plus NPH alone at bedtime for 8 weeks (LP + N) followed by preprandial H or M, plus NPH alone at bedtime for 8 weeks (H/M), or the opposite sequence. Assessments included 8-point self-monitored BG profiles, HbA(1c), and hypoglycemia (any sign or symptom of hypoglycemia or BG < 3.0 mmol/L [<54.0 mg/dL]). The primary outcome measure was the late postprandial BG value, calculated as the mean of the combined prelunch (late postbreakfast), predinner (late postlunch), and bedtime (late postdinner) values.. A total of 89 patients with type 1 DM were enrolled (44 men, 45 women; mean [SD] age, 38.3 [12.8] years; mean [SD] body weight, 70.8 [11.6] kg; mean [SD] body mass index, 24.6 [3.0] kg/m(2); mean [SD] duration of diabetes, 17.8 [10.5] years; mean HbA(1c), 7.9% [0.88%]). The mean (SD) late postprandial BG values were similar between treatments (8.9 [2.1] mmol/L [160.3 (37.8) mg/dL] for H/M vs 9.0 [1.8] mmol/L [162.1 (32.4) mg/dL] for LP + N), as were the end point HbA(1c) values (7.8% [0.9%] for H/M vs 7.9% [0.8%] for LP + N). The rate of hypoglycemia was significantly higher during treatment with H/M, primarily because of episodes occurring between 12 PM and 6 PM, but was relatively low in both groups (mean/median rate per patient per 30 days: 2.87/2.14 for H/M and 2.11/1.07 for LP + N; P < 0.05).. In this population of patients with type 1 DM, preprandial H/M provided an effective alternative regimen for prandial and basal insulin replacement. Late postprandial BG control, an indicator of basal insulin sufficiency, was similar to that achieved with an intensified regimen of LP + N injected separately before meals, and the end point HbA(1c) was similar between the 2 treatments.

Topics: Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Male; Postprandial Period; Time Factors

To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy.. In this multinational, double-blind, randomised, crossover trial, 155 patients with Type 1 diabetes (HbA(1c) < 8.0%) were symmetrically randomised to two 16-week treatment periods on either type of insulin, both injected 0-5 min before meals. NPH insulin was given as basal insulin once or twice daily as needed, and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control. Treatment periods were separated by a 4-week washout.. The rate of major nocturnal (24.00-06.00 h) hypoglycaemic episodes was 72% lower with insulin aspart than with human insulin (0.067 vs. 0.225 events/month; P = 0.001). Total rate of major hypoglycaemia did not differ significantly between treatments (insulin aspart/human insulin relative risk 0.72; 95% CI 0.47-1.09, P = 0.12). The rate of minor events was significantly reduced by 7% with insulin aspart (P = 0.048). Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control: Mean HbA(1c) remained constant, slightly below 7.7% on both treatments.. The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy.

Topics: Adolescent; Adult; Aged; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

The purpose of this trial was to compare the effects of QD basal insulin replacement using insulin detemir versus neutral protamine Hagedorn (NPH) insulin in basal-bolus therapy in combination with regular human insulin (HI) in patients with type 1 diabetes mellitus (DM).. This was a 6-month, prospective, randomized, open-label, controlled, parallel-group trial conducted at 92 sites in Europe and Australia. The trial population included men and women with type 1 DM for at least 1 year aged > or = 18 years with glycosylated hemoglobin (HbA(1c)) <== 12% already taking QD basal-bolus treatment with an intermediate- or long-acting insulin and a fast-acting human insulin or insulin analogue as bolus insulin. Patients were randomly assigned (2:1) to 6 months of treatment with insulin detemir or NPH at bedtime in combination with HI with main meals. Main outcome measures were blood glucose control as assessed by HbA(1c), fasting plasma glucose (FPG), 9-point self-monitored blood glucose (SMBG) profiles, 24-hour continuous blood glucose profiles, hypoglycemia, weight gain, and adverse events.. Of the 749 patients randomized to treatment, 747 were exposed to trial products and included in the intent-to-treat analysis set. Seven hundred patients completed the trial: 465 (94.7%) in the insulin detemir group and 235 (91.8%) in the NPH group. After 6 months, FPG was lower with insulin detemir than with NPH (-1.16 mmol/L difference; P = 0.001), whereas HbA(1c) did not differ significantly between treatments (-0.12% [95% CI, -0.25 to 0.02]; P = NS). Day-to-day variability in self-measured fasting blood glucose was lower with insulin detemir (SD, 2.82 vs 3.60 mmol/L; P < 0.001). The overall shape of the 9-point SMBG profiles differed significantly between treatments (P = 0.006), with lower glucose levels before breakfast with insulin detemir than with NPH (P < 0.001). There was a 26% reduction in the relative risk of nocturnal hypoglycemia with insulin detemir compared with NPH (P = 0.003). Gain in body weight was significantly lower after 6 months with insulin detemir than with NPH (-0.54 kg difference; P = 0.024). The frequency and type of adverse events were similar between treatment groups.. In this study, QD administration of insulin detemir at bedtime resulted in lower fasting blood glucose levels with less day-to-day variability and less fluctuation from ean blood glucose levels over 24 hours than NPH insulin, combined with an overall reduction in the risk of nocturnal hypoglycemia. These findings suggest that evening administration of insulin detemir may provide an opportunity to further improve fasting blood glucose targets.

Topics: Adult; Blood Glucose; Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies

The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin.. In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively.. Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA1c: 7.88% vs 8.11%; mean difference: -0.22% point [95% CI: -0.34 to -0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA1c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001).. Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

Insulin glulisine is a novel analog of human insulin designed for use as a rapid-acting insulin. This study compared the safety and efficacy of glulisine with regular human insulin (RHI) in combination with NPH insulin.. In total, 876 relatively well-controlled patients with type 2 diabetes (mean HbA1c 7.55%) were randomized and treated with glulisine/NPH (n = 435) or RHI/NPH (n = 441) for up to 26 weeks in this randomized, multicenter, multinational, open-label, parallel-group study. Subjects were allowed to continue the same dose of prestudy regimens of oral antidiabetic agent (OAD) therapy (unless hypoglycemia necessitated a dose change).. A slightly greater reduction from baseline to end point of HbA1c was seen in the glulisine group versus RHI (-0.46 vs. -0.30% with RHI; P = 0.0029). Also, at end point, lower postbreakfast (156 vs. 162 mg/dl [8.66 vs. 9.02 mmol/l]; P < 0.05) and postdinner (154 vs. 163 mg/dl [8.54 vs. 9.05 mmol/l]; P < 0.05) blood glucose levels were noted. Symptomatic hypoglycemia (overall, nocturnal, and severe) and weight gain were comparable between the two treatment groups. There were no between-group differences in baseline-to-end point changes in insulin dose.. Twice-daily glulisine associated with NPH can provide small improvements in glycemic control compared with RHI in patients with type 2 diabetes who are already relatively well controlled on insulin alone or insulin plus OADs. The clinical relevance of such a difference remains to be established.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin, Isophane; International Cooperation; Male; Middle Aged; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Single-Blind Method; Treatment Outcome

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

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

This trial compared the long-term safety and efficacy of the basal insulin preparations, insulin detemir and NPH insulin, in basal-bolus therapy for patients with type 1 diabetes.. This multinational open, parallel-group trial randomized patients to receive insulin detemir or NPH insulin twice daily in addition to mealtime human soluble insulin. Doses were titrated towards predefined glycemic targets. After an initial 6-month treatment period, patients were invited to participate in a 6-month extension period. A total of 289 from 421 elected to continue in the trial, of which 252 completed.. Glycemic control as assessed by hemoglobin A1c (insulin detemir, 7.88%; NPH insulin, 7.78%; difference not significant) and fasting plasma glucose (insulin detemir, 10.1 mmol/L; NPH insulin, 9.84 mmol/L; difference not significant) was similar in both treatment groups at end point, with hemoglobin A1c little changed from baseline and fasting plasma glucose slightly decreased. There was some evidence for a risk reduction for hypoglycemia in association with insulin detemir, although this was not statistically significant (relative risk overall hypoglycemia, 0.71, P = 0.139; relative risk nocturnal hypoglycemia, 0.71, P = 0.067), and hypoglycemic events were fewer in each of the 12 months. There was a significant treatment difference with regard to weight outcome; NPH insulin was associated with weight gain (1.4 kg), but there was no mean weight gain (-0.3 kg) in the insulin detemir cohort (baseline-adjusted between-group difference at 12 months, 1.66 kg, P = 0.002). There were no obvious between-group differences in other safety parameters.. Glycemic control is maintained with insulin detemir during long-term treatment. At equivalent glycemic control to NPH insulin, insulin detemir is associated with a lack of weight gain and a trend towards a reduced risk of nocturnal hypoglycemia when used in basal-bolus therapy with mealtime soluble human insulin.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Middle Aged

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

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

Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals.. This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively.. After 6 months, comparable HbA(1c) levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (-0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300-0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P = 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001).. Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.

Topics: Adult; Blood Glucose; Body Weight; Carrier Proteins; Diabetes Mellitus, Type 1; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Risk Factors

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

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

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

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

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

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

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

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

Nonfasting plasma glucose is claimed to be a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. In this study we compared the efficacy and safety profile of two different intensive insulin treatment strategies in patients with uncontrolled type 2 diabetes despite using a twice-daily insulin regimen.. We studied 60 insulin-treated patients who had uncontrolled type 2 diabetes. The study was a 6-month, open-label, randomised, parallel clinical trial conducted in two diabetes centres. The main end-points for analysis were weekly self-monitored blood glucose readings, HbA1c levels, total daily insulin dose, weight gain and the number of hypoglycaemic episodes.. The breakfast 2-h, lunch 2-h and dinner 2-h postprandial glucose values and pre-dinner glucose values were significantly lower in the Lispro group than the regular insulin group. The HbA1c value at the end of the study was significantly lower in the Lispro group (7.3 +/- 0.7%) compared with the regular insulin group (7.7 +/- 0.7%; P<0.05). Mean insulin doses were similar in the treatment groups initially and at the end. There was a statistically significant increase in insulin dose in both groups from baseline to the end of the study (P<0.05). Overall hypoglycaemia rates were comparably low and similar in both groups during the study.. We have shown that mealtime insulin Lispro plus additional lunch and bedtime NPH insulin is superior to premeal regular insulin plus bedtime NPH insulin for overall glycaemic regulation with similar weight gain and comparable rates of hypoglycaemia.

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Middle Aged; Safety; Time Factors; Treatment Outcome

Biphasic insulin aspart 30 (BIAsp30) is a dual release formulation, containing 30% soluble and 70% protamine-crystallized insulin aspart. This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents (OHAs), NPH insulin or a combination of both.. In this 16-week multinational, parallel-group, double-blind trial, 403 such patients were randomized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals. OHAs were discontinued at randomization. Efficacy was assessed by glycosylated haemoglobin (HbA1c) and self-recorded daily 8-point blood glucose (BG) profiles. Hypoglycaemic and other adverse events were the chosen safety parameters.. HbA1c concentration decreased by >0.6% (p < 0.0001 vs. baseline) in both groups, with metabolic control continuing to improve throughout the trial without reaching a stable level. Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA1c (0.78%) than those randomized to twice daily NPH insulin (0.58%; p = 0.03). BIAsp30 decreased mean daily postprandial glycaemic exposure to a greater extent than NPH insulin (mean difference = 0.69 mmol/l; p < 0.0001), reflecting greater decreases in the postbreakfast and postdinner increments (of 1.26 and 1.33 mmol/l, respectively), although postlunch increment was relatively increased (by 0.56 mmol/l). Despite the greater reduction in overall postprandial glycaemic exposure in the BIAsp30 group, the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with <2% of patients experiencing major hypoglycaemia, and approximately 33% reporting minor hypoglycaemic episodes, in both groups.. Twice daily BIAsp30 reduced postprandial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA1c in patients with type 2 diabetes. Both insulins were well tolerated. In patients poorly controlled on OHAs or NPH alone, glycaemic control can be improved by switching to twice daily BIAsp30, without increasing hypoglycaemic risk.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Treatment Outcome

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

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

This study was performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night.. The study was a 10-month multicenter, randomized, crossover trial. After a 2-month run-in period, subjects injected NPH insulin once (1 x NPH) or twice (2 x NPH) daily for 4 months in a randomized order. Adult patients were included if they had HbA(1c) levels <8.5%. Efficacy measures were HbA(1c) levels, 8-point glucose profiles, and the frequency of hypoglycemia. The statistical analysis included a within-patient comparison for crossover trials.. In all, 104 patients completed the trial. The mean HbA(1c) level before randomization was 7.1 +/- 0.85%. The HbA(1c) levels did not change significantly within patients (t test, mean difference = 0.06%; 95% confidence interval [CI] -0.073 to 0.20). The pre-dinner blood glucose values were significantly lower during the 2 x NPH daily protocol, with a mean difference of 0.76 mmol/l (t test, P = 0.004; CI 0.25 to 1.3). In the evening, the frequency of hypoglycemia increased significantly during the 2 x NPH daily protocol with a median difference of 0.56 mild episodes/30 days (P = 0.001) and 6.9 severe episodes/patient year (P = 0.007), respectively.. Equal HbA(1c) levels and increasing frequencies of hypoglycemia in the evening overshadow the slight improvement of the evening glucose profiles during a regimen with 2 x NPH daily insulin. Therefore, generalized use of a second injection of NPH insulin at lunchtime cannot be recommended to all adult patients with type 1 diabetes using intensive insulin lispro therapy.

Topics: Adult; Blood Glucose; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male

Intensive insulin treatment of type 1 diabetes mellitus increases the risk for nocturnal hypoglycemia.. To demonstrate that splitting the evening insulin regimen reduces the risk for nocturnal hypoglycemia in intensive treatment of type 1 diabetes mellitus.. Randomized, open, two-treatment crossover trial in two 4-month periods.. University research center in Italy.. 22 C-peptide-negative persons with type 1 diabetes mellitus (mean age [+/-SD], 29 +/- 3 years).. Each patient was randomly assigned to one of two insulin regimens for 4 months and then switched to the other regimen for another 4 months. The two treatment regimens were 1) mixed treatment--a mixture of human regular and neutral protamine Hagedorn (NPH) insulin administered before dinner and 2) split treatment--human regular insulin administered at dinner and NPH insulin administered at bedtime.. Frequency of nocturnal hypoglycemia. Secondary end points were levels of fasting blood glucose and hemoglobin A1c and responses to experimental hypoglycemia.. During the split-regimen treatment period, patients had fewer episodes of nocturnal hypoglycemia (mean [+/-SE], 0.10 +/- 0.02 episode/patient-day vs. 0.28 +/- 0.04 episode/patient-day; P = 0.002), a lower fasting blood glucose level (mean [+/-SE], 7.6 +/- 0.2 mmol/L vs. 8.3 +/- 0.5 mmol/L [137 +/- 4 mg/dL vs. 160 +/- 8 mg/dL]; P = 0.030), less variable fasting blood glucose levels (SD range, 2.0 +/- 0.4 vs. 3.5 +/- 0.6; P = 0.001), and lower hemoglobin A1c value (mean [+/-SE], 7.0% +/- 0.11% vs. 7.5% +/- 0.15%; P = 0.004) than during the mixed regimen. Responses to experimental hypoglycemia were better preserved with the split regimen than with the mixed regimen.. When the goal of insulin therapy in type 1 diabetes mellitus is near-normoglycemia, splitting the evening insulin treatment regimen into short-acting insulin at dinner and NPH insulin at bedtime reduces the risks for nocturnal hypoglycemia and hypoglycemia unawareness and decreases the hemoglobin A1c value compared with mixing short-acting insulin and NPH insulin at dinner.

Topics: Adult; Analysis of Variance; Blood Glucose; Circadian Rhythm; Cognition Disorders; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Prospective Studies; Regression Analysis

Topics: Adult; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Prospective Studies

Insulin lispro used in an intensive basal/bolus regimen produces equivalent glycaemic control to human-soluble insulin but reduces rates of hypoglycaemia. We tested the hypothesis that the use of rapid-acting analogues might prevent the development of defective hypoglycaemic counterregulation during intensive insulin therapy.. Ten patients with type 1 diabetes (four female, mean age 33 +/- 3 years, diabetes duration 12 +/- 2 years) participated in an open, randomized cross-over study, with 2 months run-in and 4-month treatment periods using either lispro or human-soluble insulin before meals and human NPH insulin (NPH) at night. The total of reported hypoglycaemic episodes (lispro vs. soluble, 123 vs. 128) and HbA(1c) (6.1 +/- 0.2 vs. 6.6 +/- 0.2%) were similar during both treatments. At the end of each period, we measured symptomatic, counterregulatory and cognitive responses, and glycaemic thresholds during hypoglycaemia, induced with a hyperinsulinaemic clamp (blood glucose of 5, 4.5, 3.5 and 2.5 mmol/l).. We found similar overall responses of adrenaline, cortisol, growth hormone and total symptom score. Glycaemic thresholds for rises in adrenaline (3.1 +/- 0.2 vs. 3.1 +/- 0.2 mmol/l, p = 0.76), cortisol (2.2 +/- 0.1 vs. 2.2 +/- 0.1 mmol/l, p = 0.16), growth hormone (3.3 +/- 0.15 vs. 2.9 +/- 0.2 mmol/l, p = 0.13), symptoms (3.2 +/- 0.2 vs. 3.3 +/- 0.1 mmol/l, p = 0.051) and impaired cognitive function (3.0 +/- 0.2 vs. 3.0 +/-0.2 mmol/l, p = 0.20) were also similar.. Four months of intensive treatment, with insulin lispro used pre-prandially and isophane at night, produced relatively preserved but equivalent physiological responses to hypoglycaemia as those on soluble insulin. Longer periods of treatment or alternative regimens may be necessary to demonstrate beneficial effects on hypoglycaemic physiological responses.

Topics: Adult; Blood Glucose; Cognition; Cross-Over Studies; Diabetes Mellitus, Type 1; Epinephrine; Female; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Norepinephrine; Reaction Time

To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes.. People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level.. BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments.. Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.

Topics: Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety.. This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin.. The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049).. Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.

Topics: Adolescent; Adult; Blood Glucose; Carrier Proteins; Cross-Over Studies; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Kinetics; Middle Aged; Solubility

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

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

Insulin lispro is absorbed more rapidly and has a shorter duration of action than regular human insulin. It improves glycaemic control but large-scale studies are required to identify regimens that optimise efficacy and safety with local dietary habits. This study involved 1184 Italian patients with Type 1 diabetes, randomised to insulin lispro (n=586) or regular human insulin (n=598) as pre-meal bolus for 3 months. Optimisation of basal NPH insulin was carried out in both groups. The number of administrations of NPH insulin was increased when using insulin lispro but, because basal and bolus insulins were mixed before meals, the total number of injections per day was unchanged. Compliance to administration time was significantly (p<0.001) greater with insulin lispro than with regular human insulin. Post-prandial blood glucose levels were lower with insulin lispro after breakfast (p<0.001), lunch (p<0.005) and dinner (p<0.001). The HbA1c level was decreased from baseline by both insulins, but the percent increase in patients with acceptable (<8%) HbA1c was greater with insulin lispro. While frequency of hypoglycaemia was decreased from baseline by both insulins, the proportion of episodes classified as severe was significantly increased from baseline with regular human insulin, but not with insulin lispro. Thus, compared with regular human insulin, improved glycaemic control was achieved with insulin lispro without an increase in severe hypoglyeaemia.

Topics: Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Patient Compliance; Safety; Treatment Outcome

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

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

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

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

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

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

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

To directly compare the rate of hypoglycemia and metabolic control achieved on once-daily ultralente insulin administration with twice-daily NPH insulin administration in patients with type 2 diabetes. Patient treatment satisfaction and quality of life were also examined before and during each treatment.. A crossover study was performed involving five centers and 79 patients with type 2 diabetes (fasting blood glucose > 8 mmol/l) with a 2-month run-in followed by two 6-month periods of either NPH or ultralente insulin administration. Patients were managed by a specialist nurse using a dosage adjustment protocol.. HbA1c was lower with NPH insulin therapy during each of the 6-month periods (9.7 +/- 0.2 vs. 9.1 +/- 0.3 and 9.8 +/- 0.2 vs. 9.0 +/- 0.3 mmol/l; both P < 0.01). The difference was accounted for by higher evening glucose levels with ultralente insulin (fasting 8.2 +/- 0.3 vs. 8.2 +/- 0.3 mmol/l, 6:00 P.M. 11.5 +/- 0.4 vs. 10.6 +/- 0.4 mmol/l). Despite worse control, the total number of hypoglycemic episodes was greater with ultralente insulin (220 vs. 171), and hypoglycemic episodes requiring third-party assistance occurred almost entirely with ultralente (14 vs. 1). Treatment satisfaction scores increased more with NPH insulin compared with ultralente and rose further upon changing to NPH insulin, but fell upon changing to ultralente insulin. These changes were highly significant (P < 0.001). Diabetes quality of life improved on both regimens.. These data clearly demonstrate the lower hypoglycemia rate, better glucose control, and greater treatment satisfaction accompanying therapy for type 2 diabetes with twice daily NPH compared with once daily ultralente insulin.

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

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

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

To evaluate a multiple daily injections (MDI) regimen combining lispro with multiple NPH insulin injections in order to replace basal insulin optimally.. Twenty-five C-peptide negative Type 1 patients already trained to MDI were randomized to lispro (lispro + NPH 5 min before breakfast and lunch, lispro before dinner, NPH at bedtime) or soluble insulin (20-30 min before each meal and NPH at bed-time) for 3 months before crossing over to the other regimen for another 3 months. The mean initial HbA1c level was 8.32+/-1.5%.. The variability of capillary blood glucose values was significantly lower with lispro (MAGE 0.75+/-0.36 g/l vs. 0.99+/-0.50, P<0.01; MODD 0.64+/-0.26 g/l vs. 0.80+/-0.40, P<0.05). There was a nonsignificant reduction in HbA1c with lispro: -0.40+/-0.86 vs. -0.08+/-0.71. Mean daily blood glucose levels were significantly lower with lispro (1.53+/-0.48 g/l vs. 1.82+/-0.57 g/l, P<0.05). The frequency of all hypoglycaemic episodes was the same with both regimens but the number of severe hypoglycaemic events was reduced with lispro, P = 0.048. At the end of the study, 75% of the patients chose the lispro associated with multiple NPH regimen for their own treatment. The total insulin doses was the same with both regimens but the proportion of NPH was higher with lispro (53% vs. 34%).. An MDI regimen using lispro combined with multiple NPH compared to a standard MDI regimen using soluble insulin reduced day-to-day blood glucose fluctuations, was generally preferred by patients and was associated with a reduced incidence of severe hypoglycaemia with no loss of overall control.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Patient Satisfaction; Solubility; Treatment Outcome

Regular insulin given with the evening meal could contribute to the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes using a multiple injection regimen. To test this hypothesis, we compared glucodynamics and free insulin levels on two separate study nights.. A total of 14 adolescents were recruited. On both nights, identical doses of regular insulin or insulin lispro were administered 30 min or 10 min, respectively, before the evening meal, using a double-blind randomized crossover study design. Doses of NPH insulin and carbohydrate content of the evening meal and snack were kept identical. Blood samples were taken every 15 min for blood glucose and every 60 min for free insulin and ketones.. After insulin lispro administration, glucose levels were significantly lower between the evening meal and the bedtime snack (analysis of variance [ANOVA] P = 0.02), and four hypoglycemic episodes were recorded. This corresponded to a higher (458 +/- 48 vs. 305 +/- 33 pmol/l, P = 0.02), earlier (64 +/- 4.6 vs. 103 +/- 12 min, P = 0.01), and shorter-lasting (245 +/- 21 vs. 365 +/- 39 min, P = 0.01) insulin peak in contrast to regular insulin. After the bedtime snack, glucose levels increased dramatically during the lispro night and stayed higher, up to 0300 in the morning (ANOVA P = 0.01), corresponding to lower mean insulin levels (146 +/- 20 vs. 184 +/- 27 pmol/l, P = 0.04). No differences were seen in glucose and insulin levels between 0300 and 0800. Four episodes of nocturnal hypoglycemia were documented after the bedtime snack during the regular insulin night, in contrast to one episode after insulin lispro. No differences in ketone levels were observed.. The replacement of regular insulin with insulin lispro may reduce the risk of late hypoglycemia, but redistribution of the evening carbohydrate may be needed to ensure good metabolic control and prevent early postprandial hypoglycemia.

Topics: Activity Cycles; Adolescent; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Ketones; Life Tables; Male; Postprandial Period

In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean+/-SEM): 16.1+/-3.1 vs 23.6+/-3.3) episodes during the last 6 weeks of treatment, p=0.03 (CSII vs NPH)) with maintenance of good glycaemic control (HbA1c 7.2+/-0.2 vs 7.1+/-0.2 %, p=0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study.

Topics: Adult; Blood Glucose; Circadian Rhythm; Cognition Disorders; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glucose; Glucose Clamp Technique; Hormones; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Infusion Pumps; Injections, Subcutaneous; Insulin; Insulin Infusion Systems; Insulin, Isophane; Male; Middle Aged; Nervous System Diseases; Patient Acceptance of Health Care; Perception

In Switzerland it is still a debatable point whether diabetics whose treatment has been changed from animal to human insulin notice premonitory symptoms of hypoglycemia to a lesser degree and whether this could be hazardous for them. In a prospective study, 18 longstanding type 1 and type 2 diabetics, treated with insulin Lente MC, were selected and observed at frequent intervals for three months. This first period was followed by a transfer to human insulin (Protaphan HM) and a close observation for another three months. Before the transfer, all patients were well informed about a possible change in premonitory symptoms of hypoglycemia. The initial dose of Protaphan HM was 10% lower than in the treatment with Lente MC. During the three month period with human insulin, we observed no change with regard to blood-sugar regulation or Hb-A1. The most important observation was that the number of hypoglycemic episodes did not change after the transfer to human insulin. There were only mild to moderate degrees of hypoglycemia, the average being three episodes per patient. The change to human insulin was without any problems for the patients: they all preferred to stay on Protaphan HM for future treatment. Also, in general practice, patients can be changed without difficulties from animal to human insulin, provided that the above-mentioned precautions are respected.

Topics: Adult; Aged; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Isophane (NPH) and lente insulin preparations have been the basis of insulin-injection regimens for many decades but were never formally compared. After a 2-mo run-in period, 82 patients were randomized to NPH (Protaphane) or lente (Monotard) insulin preparations given together with Actrapid as a twice-daily injection regimen in a double-blind study. Patients were seen monthly and crossed over after 5 mo of treatment. Control as assessed by glycosylated hemoglobin (NPH 9.2 +/- 0.1%, lente 9.3 +/- 0.1%, mean +/- SE) and fructosamine (1.55 +/- 0.02 and 1.57 +/- 0.02 mM) concentrations was identical for the two regimens as were home-collected laboratory-measured fasting blood glucose (BG) (NPH 8.8 +/- 0.5 mM, lente 9.0 +/- 0.5 mM) and mean BG (8.2 +/- 0.3 and 7.6 +/- 0.3 mM) concentrations. For both regimens, the major control problem was the BG concentration before and after breakfast. Total insulin dosage was similar (NPH 56.3 +/- 0.6 U/day, lente 57.2 +/- 0.6 U/day) with no tendency for a difference in the evening intermediate-acting dose (NPH 17.0 +/- 0.3 U/day, lente 17.0 +/- 0.3 U/day) to counter fasting hyperglycemia. Serum lipid concentrations and body weight confirmed the equivalence of control. Hypoglycemic events were recorded in personal diaries and graded by predetermined criteria. Self-treated, relative-assisted, and hospital/doctor-treated hypoglycemic events did not differ in frequency. We conclude that lente- and NPH-based twice-daily human insulin regimens give indistinguishable metabolic control.

Topics: Adult; Blood Glucose; Cholesterol; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Triglycerides

The long-term clinical and biofhemical effects of basal-bolus insulin treatment with lispro and NPH in dogs with diabetes mellitus are undocumented.. To perform a prospective pilot field study of the long-term effects of lispro and NPH on clinical signs and serum fructosamine concentrations (SFC) in dogs with diabetes mellitus.. Twelve dogs received combined lispro and NPH insulins treatment twice a day and were examined every 2 weeks for 2 months (visits 1-4), and every 4 weeks for up to 4 additional months (visits 5-8). Clinical signs and SFC were recorded at each visit. Polyuria and polydipsia (PU/PD) were scored as absent (0) or present (1).. Median (range) PU/PD scores of combined visits 5-8 (0, 0-1) were significantly lower than median scores of combined visits 1-4 (1, 0-1, p = 0.03) and at enrolment (1, 0-1, p = 0.045). Median (range) SFC of combined visits 5-8 (512 mmol/L, 401-974 mmol/L) was significantly lower than SFC of combined visits 1-4 (578 mmol/L, 302-996 mmol/L, p = 0.002) and at enrolment (662 mmol/L, 450-990 mmol/L, p = 0.03). Lispro insulin dose was significantly and negatively, albeit weakly, correlated with SFC concentration during visits 1 through 8 (r = -0.3, p = 0.013). Median duration of follow up was 6 months (range 0.5-6) and most dogs (8, 66.7%) were followed for 6 months. Four dogs withdrew from the study within 0.5-5 months because of documented or suspected hypoglycaemia, short NPH duration or sudden unexplained death. Hypoglycaemia was noted in 6 dogs.. Long-term lispro and NPH combination therapy may improve clinical and biochemical control of some diabetic dogs with comorbidities. Risk of hypoglycaemia should be addressed with close monitoring.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Prospective Studies; Protamines

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group.. Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group.. • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic.. • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

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

To prevent hypoglycemic episodes, the management of insulin therapy against post-transplant diabetes mellitus (PTDM) is important. We compared glargine (long-acting insulin) versus NPH isophane (intermediate-acting insulin) as an armamentarium against PTDM. Indeed, the study evaluated PTDM patients with hypoglycemic episodes treated with isophane or glargine.. We evaluated a total number of 231 living-donor renal transplant recipients with PTDM of age ≥ 18 years admitted to the hospital between January 2017 and September 2021. However, patients taking hypoglycemic agents before transplantation were excluded from this study. Out of 231 patients, 52 (22.15%) suffered from PTDM out of whom 26 were treated with glargine or isophane.. After applying exclusion criteria, out of 52 PTDM patients 23 were included in the study: 13 PTDM patients were treated with glargine, whereas 10 PTDM patients with isophane. Our analysis revealed 12 episodes of hypoglycemia in glargine-treated PTDM patients compared to 3 in isophane-treated PTDM patients (p = 0.056). Clinically, 9 out of 15 hypoglycemic episodes were nocturnal (60%). Furthermore, no other risk factors were observed in our study population. Detailed analysis showed that both groups had equivalent doses of immunosuppressants and oral hypoglycemic agents. The odds ratio for hypoglycemia in the group treated with isophane compared to that treated with glargine was 0.224 (95% CI, 0.032-1.559). Glargine users recorded significantly lower blood sugar levels before lunch, dinner and at bedtime with p-values of 0.001, 0.009 and 0.001 respectively. A better hemoglobin A1c (HbA1c) level was seen in the glargine vs. isophane group (6.98 ± 0.52 vs. 7.45 ± 0.49, p-value 0.03).. The study shows better blood sugar control with long-acting insulin analog, glargine, than with intermediate-actin analog, isophane. Overall, a higher number of hypoglycemic episodes was nocturnal. Long term safety of long-acting insulin analogs needs to be further studied.

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

To explore details of the incidence and rates of daytime and nocturnal hypoglycaemia, levels of hypoglycaemia, and relationship to glycated haemoglobin (HbA1c), when comparing iGlarLixi versus premixed biphasic insulin aspart 30 (BIAsp 30) in the SoliMix randomized controlled trial.. This exploratory analysis of SoliMix used logistic regression and negative binomial regression analyses to assess between-treatment differences in the incidence and rates of hypoglycaemia by time of day. A negative binomial model was used to derive estimated annualized hypoglycaemia rates as a function of HbA1c.. iGlarLixi was associated with lower incidence and rates of American Diabetes Association Level 2 (<54 mg/dL [<3.0 mmol/L]) hypoglycaemia during both night and day versus BIAsp 30. Incidence and rates of Level 1 (<70 to ≥54 mg/dL [<3.9 to ≥3.0 mmol/L]) hypoglycaemia were also mostly shown to be reduced with iGlarLixi versus BIAsp 30. Severe (Level 3) events were too few for analysis (n = 3). iGlarLixi was associated with lower modelled event rates of Level 2 and Level 1 hypoglycaemia over a wide range of HbA1c levels versus BIAsp 30.. These results show that the lower HbA1c levels and weight benefit seen with iGlarLixi versus premixed BIAsp 30 in people with type 2 diabetes advancing their basal insulin therapy in the SoliMix trial are also accompanied by a lower risk of hypoglycaemia at any time of day and across a broad range of HbA1c levels.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane

Though initiation of insulin results in a significant change in glycemic levels, treating patients without significant hypoglycemic events remains difficult in diabetes patients initiated with different insulin-based regimens. This study assessed the association of hypoglycemic incidence and glycemic control between NPH and premixed insulin regimens in patients with type 2 diabetes mellitus (T2DM).. This was a retrospective observational study in patients with T2DM who were treated with insulin-based therapy from 2015 to 2020 at the University of Gondar Comprehensive Specialized hospital. Average fasting blood glucose (FBG) between NPH and premixed insulin regimens was compared using an independent t-test. The Association of NPH and premixed insulin regimens with hypoglycemic incidences and glycemic control was examined by a logistic regression model. P < 0.05 was statistically significant.. From 405 participants, more than half (55.3%) were males with a mean age of 59.2(±9.1) years. Baseline mean HbA1C and FBG levels were 12.73(±1.1) % and 347.7(±48.5) mg/dl, respectively. Within a one-year follow-up period of insulin initiation, the rate of hypoglycemia was 13.1%. The incidence of hypoglycemia was significantly higher in patients initiated with premixed insulin compared with NPH insulin regimens (P < 0.001). After one year of insulin initiation, HbA1C decreased from 12.7 to 7.6 and from 12.8 to 7.3% and FBG levels decreased from 347.5 to 160.7 and from 348.2 to 147.3 mg/dl following initiation of NPH and premixed insulin, respectively. Patients treated with premixed-based insulin were found more likely to achieve target FBG compared with patients treated with NPH insulin regimens after one year of initiation (P = 0.02).. Premixed insulin-based regimen has found to have a higher hypoglycemic incidence, but a better level of glycemic control compared to NPH insulin-based therapy. Therefore, patients initiated with premixed insulin need to be highly vigilant and motivated to recognize the symptoms of hypoglycemia.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Ethiopia; Female; Glycated Hemoglobin; Glycemic Control; Hospitals; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged

Topics: Comorbidity; COVID-19; COVID-19 Drug Treatment; Dexamethasone; Diabetes Mellitus; Glycemic Control; Humans; Hypoglycemia; Insulin, Isophane; SARS-CoV-2

Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use.. To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings.. This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019.. Insulin glargine, insulin detemir, and NPH insulin.. The primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age.. Of the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use.. In this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.

Topics: Aged; Aged, 80 and over; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Proportional Hazards Models; Retrospective Studies

To determine whether basal insulin analogs reduce the rate of composite neonatal morbidity compared with neutral protamine Hagedorn (NPH) in women with type 2 diabetes mellitus (T2DM).. This was a retrospective cohort study of women with T2DM and singleton pregnancy at a single tertiary center. Primary outcome was a composite neonatal morbidity of any of the following: shoulder dystocia, large for gestational age, neonatal intensive care unit admission, neonatal hypoglycemia, or respiratory distress syndrome. Secondary outcomes were rates of maternal hypoglycemic events, hypertensive disorders, preterm birth, and primary cesarean delivery. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated.. Of 233 women with T2DM that met the inclusion criteria, 114 (49%) were treated with basal insulin analogs and 119 (51%) with NPH. The rate of composite neonatal morbidity was similar between groups (73 vs. 60%; aRR: 1.18; 95% CI: 0.92-1.51). There were no differences in the rates of maternal adverse outcomes between the groups. Basal insulin analog was associated with a lower rate of primary cesarean delivery as compared with NPH (21 vs. 36%; aRR: 0.44; 95% CI: 0.25-0.78).. Among pregnant women with T2DM managed with either basal or NPH insulin regimen, the rates of composite neonatal morbidity and maternal complications were similar.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Infant, Newborn, Diseases; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Logistic Models; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Premature Birth; Retrospective Studies; Young Adult

NPH insulin holds its own against basal insulin analogs-and it's cheaper.

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

To assess the financial consequences of different adoption rate of Biphasic Insulin Aspart (BIAsp) 30 instead of Biphasic Human Insulin (BHI) 30 for people with type 2 diabetes (T2DM) in Thailand from the payer's perspective.. The Excel-based International T2DM Budget Impact Model over a 3-year period was used. The cohort was the T2DM patients who received treatment from government hospitals under the Universal Health Coverage Scheme. Demographic, the adverse events, and the costs were derived from published studies in Thailand. Efficacy was based on meta-analysis. Adoption rates were assumed to increase each year. Net budget impact (NBI) and one-way sensitivity were analyzed.. Hypoglycemia costs were lower in BIAsp 30 compared with BHI 30. The NBI per year was 26,511,269 THB (771,349 USD) for year 1, 52,181,133 THB (1,518,218 USD) for year 2, and 76,189,608 THB (2,216,747 USD) for year 3. The NBI per insulin user per year was 33.45 THB (0.97 USD), 67.27 THB (1.96 USD), 101.49 THB (2.95 USD) from year 1 to year 3, respectively Conclusions: Lower rate of hypoglycemia with BIAsp 30 than those treated with BHI 30 generates cost savings resulting in significant deduction in the additional acquisition cost of BIAsp 30. Therefore, the NBI per insulin user per year has become small.

Topics: Biphasic Insulins; Budgets; Cohort Studies; Cost Savings; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Outcome Assessment, Health Care; Thailand; Treatment Outcome

To compare dipeptidyl peptidase-4 (DPP-4) inhibitors with neutral protamine Hagedorn (NPH) insulin, in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (DM2) not controlled on metformin and sulfonylureas.. A retrospective cohort study of individuals with DM2 newly dispensed with either DPP-4 inhibitors or NPH as third-line therapy, after metformin and sulfonylurea. Treatment discontinuation, macrovascular outcomes, and hypoglycemia were compared using multivariable Cox regression models, adjusted for sex, age, year of cohort entry, place of residence, hypertension, past history of hypoglycemia, diabetic ketoacidosis, comorbidities, and number of visits to emergency departments, outpatient physician, and hospitalizations.. Treatment discontinuation and hypoglycemia occurred more frequently with NPH than with DPP-4 inhibitor users. In the adjusted Cox model, the use of NPH compared to that of DPP-4 inhibitors was associated with a higher risk of discontinuation (HR: 1.33; 95% CI 1.27-1.40) and hypoglycemia (HR: 2.98; 95% CI 2.72-3.28). Risk of cardiovascular events was similar across groups.. This real-world analysis suggests that DM2 patients initiating third-line therapy with NPH have poorer control of diabetes when compared to DPP-4 inhibitor initiators.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Retrospective Studies; Sulfonylurea Compounds; Withholding Treatment

In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ from trial results.. To compare the rates of hypoglycemia-related emergency department (ED) visits or hospital admissions associated with initiation of long-acting insulin analogs vs human NPH insulin in patients with type 2 diabetes.. A retrospective observational study using data from Kaiser Permanente of Northern California from January 1, 2006, through September 30, 2015. Patients with type 2 diabetes who initiated a long-acting insulin analog or NPH insulin were included and censored at death, loss of health plan coverage, change in insulin treatment, or study end on September 30, 2015.. Initiation of basal insulin analogs (glargine or detemir) vs NPH insulin.. The primary outcome was the time to a hypoglycemia-related ED visit or hospital admission and the secondary outcome was the change in hemoglobin A1c level within 1 year of insulin initiation.. There were 25 489 patients with type 2 diabetes who initiated basal insulin therapy (mean age, 60.2 [SD, 11.8] years; 51.9% white; 46.8% female). During a mean follow-up of 1.7 years, there were 39 hypoglycemia-related ED visits or hospital admissions among 1928 patients who initiated insulin analogs (11.9 events [95% CI, 8.1 to 15.6] per 1000 person-years) compared with 354 hypoglycemia-related ED visits or hospital admissions among 23 561 patients who initiated NPH insulin (8.8 events [95% CI, 7.9 to 9.8] per 1000 person-years) (between-group difference, 3.1 events [95% CI, -1.5 to 7.7] per 1000 person-years; P = .07). Among 4428 patients matched by propensity score, the adjusted hazard ratio was 1.16 (95% CI, 0.71 to 1.78) for hypoglycemia-related ED visits or hospital admissions associated with insulin analog use. Within 1 year of insulin initiation, hemoglobin A1c level decreased from 9.4% (95% CI, 9.3% to 9.5%) to 8.2% (95% CI, 8.1% to 8.2%) after initiation of insulin analogs and from 9.4% (95% CI, 9.3% to 9.5%) to 7.9% (95% CI, 7.9% to 8.0%) after initiation of NPH insulin (adjusted difference-in-differences for glycemic control, -0.22% [95% CI, -0.09% to -0.37%]).. Among patients with type 2 diabetes, initiation of a basal insulin analog compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related ED visits or hospital admissions or with improved glycemic control. These findings suggest that the use of basal insulin analogs in usual practice settings may not be associated with clinical advantages for these outcomes.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Emergency Service, Hospital; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Retrospective Studies

Reasonable glycemic control is difficult to achieve in patients with diabetes mellitus (DM) receiving continuous enteral nutrition therapy (CENT). There are no solid evidence-based medicine guidelines regarding this issue in these patients. The purpose of this study was to determine if the use of a basal-bolus insulin regimen is more effective than neutral protamine Hagedorn (NPH) insulin alone in controlling blood glucose in non-critically ill patients with DM receiving CENT. We performed a retrospective, records-based review comparing basal-bolus with NPH insulin regimen in these patients, hospitalized in the internal medicine wards in our hospital. Number of hypoglycemic episodes, mean blood glucose, and time-to-target (time needed to reach 3 successive glucose readings in the appropriate target of 140-180 mg/dL) were evaluated in each regimen. Mean blood glucose was 199.22 mg/dL (95% confidence interval [CI], 179.8-218.5 mg/dL) in the basal-bolus vs 190.73 mg/dL (95% CI, 172.1-209.2 mg/dL) in the NPH insulin regimen ( P = .538). Time-to-target was an average of 3.65 ± 1.75 days in the basal-bolus group and 4.33 ± 2.42 days in the NPH group ( P = .364). There were no statistically significant differences in frequency of hypoglycemia ( P = .364). Rate of death was high (around 40%) in both groups. We conclude that hospitalized hyperglycemic patients receiving CENT can be treated by either basal-bolus or NPH insulin regimens. However, the overall glucose levels remain elevated during hospitalization irrespective of the insulin therapy. There is an urgent need to define glucose targets in this population of patients and to evaluate prospectively head-to-head different insulin protocols.

Topics: Aged; Aged, 80 and over; Blood Glucose; Critical Illness; Diabetes Mellitus, Type 2; Enteral Nutrition; Evidence-Based Medicine; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Middle Aged; Retrospective Studies

To evaluate the impact of 6 month hypoglycemia on treatment discontinuation and hospitalization of patients initiating basal insulin for type 2 diabetes (T2D) in real-world practice.. This was a retrospective cohort study of patient-level data using electronic medical records (EMRs) in the Predictive Health Intelligence diabetes dataset. Data from adult patients with T2D initiating basal insulin glargine, insulin detemir, or Neutral Protamine Hagedorn insulin between January 2008 and March 2014 was analyzed. The date of first basal insulin prescription in an outpatient setting was the index date. A 12 month baseline prior to the index date was established; follow-up was 6-24 months from the index date. Patients were assigned to cohorts by experience of hypoglycemia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code or blood glucose test) in the first 6 months following the index date; with hypoglycemia and without hypoglycemia cohorts were compared for basal insulin treatment discontinuation and hospitalization.. Overall, 49,062 patients were included; 5159 (10.5%) experienced hypoglycemia in the 6 months following basal insulin initiation. In the first 12 months, 68.1% of patients in the with hypoglycemia cohort discontinued basal insulin versus 53.9% in the without hypoglycemia cohort (p < .0001); more patients in the with hypoglycemia cohort had at least one hospitalization in the first year of follow-up (50.1% vs. 14.6%; p < .0001).. Patients with hypoglycemia soon after initiating basal insulin are at greater risk of discontinuation of their basal insulin therapy and hospitalization versus those who did not have hypoglycemic events within the first 6 months of basal insulin initiation. A limitation of this study is that it was a retrospective analysis of EMR data and the study may not be representative of all US patients with T2D on basal insulin and it cannot be assumed that every hypoglycemic event was recorded.

Topics: Aged; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Risk

Investigate contributors to treatment satisfaction in type 1 diabetes (T1D).. Post-hoc analysis using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) in 771 T1D patients from two 28-week trials comparing once-daily insulin glargine 100U/mL (Gla-100) with once- or twice-daily NPH neutral protamine Hagedorn (NPH) insulin.. Gla-100 was associated with a significant improvement in treatment satisfaction versus NPH (overall population adjusted mean [standard error] DTSQs change from baseline: +1.13 [0.30] versus -0.04 [0.31]; p=0.006). In the overall population, treatment satisfaction improvement with all insulin regimens was related to less frequent severe hypoglycemia (coefficient-0.077; p=0.040) and HbA1c reduction (-0.066; p=0.082). By treatment regimen, relationships between treatment satisfaction and these outcomes approached or attained statistical significance for NPH insulin, but not Gla-100. In the overall population, predictors of treatment satisfaction improvement included: Gla-100 treatment (estimate 1.17, p=0.006), lower baseline DTSQs (-0.57, p<0.001), study (-1.01, p=0.019), lower severe hypoglycemia rate (0.17, p=0.012), and higher baseline HbA1c (0.44, p=0.014). By treatment regimen, these predictors remained significant for NPH insulin.. Gla-100 resulted in a significant improvement in treatment satisfaction versus NPH insulin, independent of baseline disease characteristics and clinical outcomes.

Topics: Adult; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Drug Resistance; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index

The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.. All persons aged 18-65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006-2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.. A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040).. Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults. KEY MESSAGES The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear. Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin. Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Topics: Adult; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; Young Adult

To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study.. In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c ≥ 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months.. A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% ± 2.1%) and detemir groups (2.2% ± 2.1%) was higher than that in the NPH group (2.0% ± 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 ± 2.9 kg) compared with the glargine (+0.1 ± 3.0 kg) and NPH (+0.3 ± 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis.. In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

Topics: China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Intention to Treat Analysis; Lost to Follow-Up; Prospective Studies; Registries; Severity of Illness Index; Weight Gain

To identify patient-related characteristics and other impact factors predicting early discontinuation of basal insulin therapy in type 2 diabetes in primary care.. A total of 4837 patients who started basal insulin therapy (glargine: n=3175; NPH: n=1662) in 1072 general and internal medicine practices throughout Germany were retrospectively analyzed (Disease Analyser Database: 01/2008-03/2014). Early discontinuation was defined as switching back to oral antidiabetic drugs (OAD) therapy within 90 days after first basal insulin prescription (index date, ID). Patient records were assessed 365 days prior and post ID. Logistic regression models were used to adjust for age, sex, diabetes duration, diabetologist care, disease management program participation, HbA1c, and comorbidity.. Within 3 months after ID, 202 (6.8%) of glargine patients switched back to OAD (NPH: 130 (8.5%); p<0.05). In multivariable logistic regression, predictors of early basal insulin discontinuation were ≥1 documented hypoglycemia before ID (adjusted Odds ratio; 95% CI: 2.20; 1.27-3.82), diagnosed depression (1.31; 1.01-1.70) and referrals to specialists within 90 days after ID (2.06; 1.61-2.63). Diabetologist care (0.57; 0.36-0.89) and glargine treatment (vs. NPH: 0.78; 0.61-0.98) were related to a lower odds of having early insulin discontinuation.. Less than 10% of type 2 diabetes patients switched back to oral antidiabetic drugs within 90 days after start of basal insulin therapy. In particular, patients with baseline depression and frequent or severe hypoglycemia have a higher likelihood for early discontinuation of basal insulin, whereas use of insulin glargine and diabetologist care are related to an increased chance of continuous insulin treatment.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Chi-Square Distribution; Depression; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Substitution; Female; Germany; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Primary Health Care; Referral and Consultation; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the basal analog insulin degludec and the rapid-acting prandial insulin aspart in a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemia in participants treated twice daily with IDegAsp or biphasic insulin aspart 30 (BIAsp 30).. Hypoglycemia data were analyzed from two similarly designed randomized controlled open-label treat-to-target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal.. Over 26 weeks, the rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between-treatment differences were more pronounced during the maintenance period (≥16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; -31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; -62%; P < 0.0001), and 0.16 (95% CI 0.04, 0.59; -84%; P = 0.0061), respectively.. Compared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin.

Topics: Aged; Biphasic Insulins; Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Maintenance Chemotherapy; Male; Middle Aged; Multicenter Studies as Topic; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Risk Factors

The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs.. Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models.. A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant.. Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.

Topics: Body Mass Index; Body Weight; Comorbidity; Costs and Cost Analysis; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Propensity Score; United Kingdom

Poor glycemic control and the resulting development of complications of type 2 diabetes (DM2T) increase treatment costs. If adequate glycemic control cannot be achieved by lifestyle modifications and oral antidiabetic (OAD) therapy, initiation of insulin therapy is recommended. Cost effectiveness of basal insulins of the type NPH or glargine in combination with OAD for the treatment of DM2T was examined in a number of pharmacoeconomic studies. However, none of these studies were conducted in the Czech Republic. Therefore, the aim of the project POET2 was to compare annual direct medical costs of treating DM2T after addition of insulin NPH or glargine to OAD therapy in a clinical practice setting in the Czech Republic.. Data collected from 1967 patients who met the criteria for inclusion into the non-interventional prospective registry POET2 (DM2T, ongoing OAD therapy, glycated hemoglobin HbA1c > 6 % IFCC) and who were observed for 12 months following the start of insulin therapy (glargine: n = 1061 vs NPH: n = 906) were analysed. Costs of treatment were analysed from the perspective of health insurance companies and included costs of medication, medical devices and medical procedures.. In both treatment groups a reduction of HbA1c (glargine group: by 1.77 % IFCC vs NPH group: by 1.73 % IFCC) and fasting plasma glucose (glargine group: by 3.67 mmol/l vs NPH group: by 3.63 mmol/l) was observed. Insulin glargine therapy was associated with the incidence of a significantly lower number of documented symptomatic hypoglycemic events (glargine group: 0.840 events per patient and year of treatment vs. NPH group: 1.053 events per patient and year of treatment; p < 0.05). Overall annual direct medical costs associated with the initiation of basal insulin treatment were higher on average by 2547.07 CZK among patients treated with insulin glargine (glargine group: 12173.09 ± 4169.44 CZK vs NPH group: 9626.02 ± 3432.79 CZK; p < 0.001) due to higher costs of medication (glargine group: 7992.97 ± 4001.81 CZK vs NPH group: 3784.2 ± 3181.48 CZK; p < 0.001). By contrast, costs of medical devices (glargine group: 2332.08 ± 917.84 CZK vs NPH group: 3893.95 ± 989.79 CZK; p < 0.001) and medical procedures (glargine group: 1848.04 ± 684.89 CZK vs NPH group: 1947.87 ± 685.43 CZK; p < 0.001) were lower among patients treated with insulin glargine.. Addition of basal insulin to OAD therapy was an efficacious therapeutic intervention for the treatment of DM2T in a clinical practice setting in the Czech Republic. Overall annual direct medical costs were higher among patients treated with insulin glargine than among patients treated with insulin NPH. However, costs of medical devices and medical procedures were lower in the insulin glargine group. In addition, incidence of hypoglycemia was significantly lower among patients treated with insulin glargine.

Topics: Adult; Aged; Czech Republic; Diabetes Mellitus, Type 2; Direct Service Costs; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Prospective Studies; Registries

This study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills-based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus.. Retrospective analysis of data from 892 DAFNE participants from 11 UK centres.. Mean HbA1c 12 months after DAFNE was lower in those using twice- rather than once-daily basal insulin after correcting for differences in baseline HbA1c , age and duration of diabetes; difference -2 (95% CI -3 to -1) mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7 to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c  ≥ 58 mmol/mol, who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice-daily basal insulin users. In the group with greatest fall in HbA1c , the estimated relative risk for severe hypoglycaemia in twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88-3.36, P = 0.110).. After structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c , independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.

Topics: Adult; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Logistic Models; Male; Middle Aged; Patient Education as Topic; Retrospective Studies; Self Care; Treatment Outcome

To identify the baseline factors associated with achievement of glycosylated haemoglobin A1c (HbA1c) < 7.0% in Chinese patients receiving biphasic insulin as part 30 (BIAsp 30), who were previously inadequately controlled with oral anti-diabetic drugs (OADs).. A1 chieve was a multinational, prospective, open-label, 24-week non-interventional study in patients with type 2 diabetes initiating insulin analogues in 28 countries. The patients were enrolled to take BIAsp 30 according to physician's clinical judgments, who was also responsible for the treatment regimen and dosage adjustment. Primary safety endpoints were the incidence of serious drug adverse reactions (SADRs) including serious hypoglycaemia. Major efficacy endpoints were change in HbA1c, fasting plasma glucose (FPG), 2h post-prandial plasma glucose (2 hPG) from baseline. Relationships between baseline predictive baseline factors and achievement of HbA1c < 7.0% after treatment were examined using multivariate analysis.. In China, 4 100 patients initiated BIAsp 30 [54.2% males, age (56.2 ± 13.6) years]. No SADRs were reported. Mean HbA1c was reduced from (9.3 ± 2.1)% to (7.0 ± 1.0)%; FPG was reduced from (10.2 ± 3.3) mmol/L to (6.8 ± 1.3) mmol/L. Changes in 2 hPG after breakfast, lunch and dinner were (-5.6 ± 4.7), (-4.9 ± 4.3) and (-4.2 ± 4.1) mmol/L, respectively (all P < 0.001). The proportion of patients achieving HbA1c < 7.0% increased from 9.7% at baseline to 54.2% at week 24. Multivariate analysis revealed a negative relationship between baseline HbA1c, FPG, 2 hPG and HbA1c < 7.0% after treatment.. In the Chinese subgroup of the A1 chieve study, lower baseline HbA1c, FPG, 2 hPG were predictive factors for achieving HbA1c < 7.0% after 24-week treatment of BIAsp 30, indicating that the earlier initiation of BIAsp 30 in patients poorly controlled with OADs, the more helpful for them to achieve treatment target.

Topics: Administration, Oral; Asian People; Biphasic Insulins; Blood Glucose; China; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Prospective Studies

Biphasic insulin aspart 30 allows fewer daily injections versus basal-bolus insulin regimens, which may improve adherence and treatment outcome. This sub-analysis of the observational A1chieve study assessed clinical safety and effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes previously receiving basal-bolus insulin regimens.. A1chieve was an international, open-label, 24-week study in people with type 2 diabetes starting/switching to biphasic insulin aspart 30, insulin detemir or insulin aspart. This sub-analysis assessed patients switching from insulin glargine- or neutral protamine Hagedorn insulin-based basal-bolus insulin regimens to biphasic insulin aspart 30.. 1024 patients were included. At 24 weeks, glycated haemoglobin and fasting plasma glucose were significantly reduced from baseline in both cohorts (all p<0.001). The proportion reporting any hypoglycaemia, major hypoglycaemia or nocturnal hypoglycaemia was significantly reduced after 24 weeks (all p<0.05). No serious adverse drug reactions were reported. Both cohorts had significantly improved health-related quality of life (HRQoL; p<0.001).. 24 weeks after switching from basal-bolus insulin regimens to biphasic insulin aspart 30, glycaemic control and HRQoL were significantly improved, and hypoglycaemia was significantly reduced. This suggests that people with type 2 diabetes inadequately controlled on basal-bolus insulin regimens can consider biphasic insulin aspart 30.

Topics: Adult; Africa, Northern; Aged; Asia; Biomarkers; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Latin America; Male; Middle Aged; Middle East; Quality of Life; Russia; Time Factors; Treatment Outcome

The aim was to observe the effects of switching from neutral protamine Hagedorn (NPH) insulin to insulin glargine on glycaemic control in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice in Italy. This multicenter, observational, retrospective study included 1,011 patients with T2DM who switched from NPH insulin to glargine or were maintained on NPH insulin. The primary outcome was change in HbA1c over 4-8 months. Secondary outcomes included fasting blood glucose (FBG), insulin dose, and hypoglycaemia. The intention-to-treat population consisted of 996 patients (glargine 496; NPH 500). Prior to switching, HbA1c was higher in the glargine than the NPH group [mean (±SD) 8.8 ± 1.4 vs. 7.9 ± 1.2%; p < 0.001]. HbA1c decreased after 4-8 months with glargine (8.2 ± 1.4%; p < 0.001) but not with NPH (8.0 ± 1.4%; p = 0.20). Similar results were observed for FBG. The daily dose of glargine increased from 0.22 ± 0.10 U/kg at the switch to 0.26 ± 0.11 U/kg at study end, while the NPH dose remained stable (0.19 ± 0.09-0.20 ± 0.09 U/kg). While not statistically significant, the percentage of patients with hypoglycaemic episodes during the last month of treatment tended to be less with glargine. No significant change in body weight occurred in either group. Switching patients from NPH insulin to insulin glargine in a real-life setting was associated with significant improvement in glycaemic control. The increase in glargine dose was not accompanied by increased hypoglycaemia or weight gain.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Italy; Male; Retrospective Studies

We performed a comparative analysis of the use of long-acting insulin (analogues) neutral protamine hagedorn (NPH), detemir (Det) and glargine (Gla), and quantified injection frequencies and daily insulin doses in patients with type 1 and 2 diabetes in daily practice.. A total number of 51 964 patients from 336 centres in Germany and Austria with type 1 and 2 diabetes with exclusive insulin therapy were retrospectively analysed.. A total number of 42.1%/75.9% (type 1/type 2) of patients used NPH, 19.9%/6.7% Det and 38.0%/17.4% Gla, with similar glycaemic control and proportion of severe hypoglycaemia for NPH/Det/Gla in type 1 (Mean HbA(1c) 7.98%/7.98%/8.07%; mean proportion of severe hypoglycaemia 11.06%/11.93%/10.86%) and type 2 diabetes (Mean HbA(1c) 7.61%/7.78%/7.61%; mean proportion of severe hypoglycaemia 5.66%/4.48%/5.03%). In type 1 diabetes, the mean daily injection frequencies of NPH versus Det versus Gla were 1.9 vs 1.8 vs 1.1, and total daily insulin injections were 5.3 vs 5.6 vs 5.0. The adjusted mean daily basal insulin doses were 0.36, 0.39 and 0.31 IU/kg, mean daily total insulin dose was lowest for Gla (0.74 IU/kg), followed by NPH (0.76 IU/kg) and Det (0.81 IU/kg). In type 2 diabetes patients, mean daily injection frequencies were 1.6 for NPH, 1.4 for Det and 1.1 for Gla, total daily insulin injections were 4.0 vs 4.1 vs 3.6. The mean daily basal insulin dosages were 0.30 IU/kg (NPH), 0.33 IU/kg (Det) and 0.29 IU/kg (Gla), mean total insulin doses per day were 0.63 IU/kg (NPH), 0.77 IU/kg (Det) and 0.67 IU/kg (Gla).. In a 'real-world' setting, the injection frequencies and doses of basal and total insulin per day are lowest with the use of insulin glargine compared with NPH-insulin or insulin detemir at similar glycaemic control and rates of severe hypoglycaemia.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies

Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM.. Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0-18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 ± 3.8 years; 53% males; diabetes duration 5.6 ± 3.5 years; HbA1c 7.9 ± 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/100 py, respectively. The risk of SH was higher in females (IRR = 1.44; 95%CI 1.04-1.99), in patients using rapid acting analogues as compared to regular insulin (IRR = 1.48; 95%CI 0.97-2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR = 0.40; 95%CI 0.19-0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR = 4.25; 95%CI 1.01-17.86) and increased with insulin units needed (IRR = 7.66; 95%CI 2.83-20.74) and HbA1c levels (IRR = 1.63; 95%CI 1.36-1.95). Mother's age was inversely associated with the risk of both SH (IRR = 0.95; 95%CI 0.92-0.98) and DKA (IRR = 0.94; 95%CI 0.88-0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR = 1.48; 95%CI 0.97-2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect.. The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Infant; Insulin; Insulin, Isophane; Italy; Ketosis; Male; Retrospective Studies

Topics: Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics

The management of type 2 diabetes mellitus in long-term care (LTC) settings can be complex as a result of age-related complications. Despite guideline recommendations, sliding scale insulin remains commonplace in the LTC setting and data on basal insulin use are lacking.. This retrospective study used medical chart data and the Minimum Data Set from elderly LTC facility patients who received basal insulin (insulin glargine, insulin detemir, or neutral protamine Hagedorn insulin) for the treatment of diabetes, to investigate the practice patterns and associated clinical outcomes.. A total of 2,096 elderly, insulin-treated patients in LTC were identified, with 59.5% of them (N=1,247) receiving basal insulin. Of these, more than 50% of patients received sliding scale insulin in co-administration with basal insulin. Despite its ease of use, insulin pen use was very low, at 14.6%. Significant differences were observed between the basal insulin groups for glycated hemoglobin level and dosing frequency. Hypoglycemia was uncommon -17.2% of patients experienced at least one event, and there was no significant difference in the prevalence of hypoglycemia between the groups.. These data suggest the underutilization of basal insulin in the LTC setting and worryingly high combinational use with sliding scale insulin. Differences in glycated hemoglobin and dosing frequencies between types of basal insulin warrant further comparative effectiveness studies.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug Utilization; Female; Glycated Hemoglobin; Homes for the Aged; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Nursing Homes; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors

To describe (i) current bedtime nutritional practices and (ii) the association between post-dinner dietary intake and the occurrence of non-severe nocturnal hypoglycemia (NH) in real-life conditions among adult patients with type 1 diabetes using insulin analogs.. One hundred adults (median [interquartile range]: age 46.4 [36.0-55.8] years, HbA1c 7.9 [7.3-8.6] % (63 [56-70] mmol/mol)) using multiple daily injections (n=67) or insulin pump (n=33) wore a blinded continuous glucose monitoring system and completed a food diary for 72-h.. NH occurred on 28% of 282 nights analyzed. (i) Patients reported post-dinner dietary intakes on 63% of the evenings. They injected rapid-acting insulin boluses on 64 occasions (23% of 282 evenings). These insulin boluses were mostly injected with (n=37) dietary intakes. (ii) Post-dinner dietary intake was not associated with NH occurrence in univariate analyses. In multivariate analyses, the injection of rapid-acting insulin modulated the association between post-dinner dietary intake and NH: with insulin, post-dinner carbohydrate intake was positively associated with NH (odds ratio (OR): 1.16 [95% confidence interval, CI: 1.04-1.29] per 5g increase, p=0.008); without insulin, post-dinner protein intake was inversely associated with NH occurrence (OR [95% CI]: 0.88 [0.78-1.00] per 2g increase, p=0.048).. NH remains frequent in adults with type 1 diabetes. There is a complex relationship between post-dinner dietary intake and NH occurrence, including the significant role of nutrient content and rapid-acting insulin injection that requires further investigation.

Topics: Adult; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Dietary Supplements; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin, Isophane; Male; Middle Aged; Monitoring, Physiologic; Postprandial Period; Quebec; Risk Factors

Early initiation of insulin therapy has widely been associated with numerous benefits, including improved glycaemic control and reduced long-term risk of developing microvascular diseases. Biphasic insulins offer a convenient option for insulin initiation, addressing both basal and postprandial insulin requirements with one injection, making them relatively simple for patients to dose. Development of biphasic insulin aspart (BIAsp) has further offered improved postprandial glycaemic control and lower rates of nocturnal and major hypoglycaemia than biphasic human insulin.. The safety and efficacy of the 30/70 rapid-acting/intermediate-acting formulation of BIAsp (BIAsp 30) in patients with type 2 diabetes was examined in the IMPROVE study, a 26-week, international, observational trial. In this subanalysis, baseline clinical factors that predicted treatment success, defined as HbA1c <7% (<53 mmol/mol) without experiencing hypoglycaemia after 26 weeks on BIAsp 30 therapy, were assessed.. The composite endpoint was defined for 44,010 (77%) patients from the total cohort of 57,478, and 28,696 of these were included in the statistical examination. The results of the analysis suggest that those with lower baseline HbA1c of ≤8% (≤64 mmol/mol), shorter duration of diabetes at baseline (<5 years) and no incidence of major hypoglycaemia at 13 weeks, or minor hypoglycaemia at 4 weeks, before the beginning of the trial were more likely to achieve treatment success.. Lower baseline HbA1c, shorter duration of diabetes and no incidence of hypoglycaemia up to 13 weeks prior to initiation are predictors of achieving HbA1c <7% without hypoglycaemia with a BIAsp 30 regimen. These results suggest that it is easier to reach target without hypoglycaemia with BIAsp 30 when prescribed earlier. As this was an observational study, lack of control groups or randomisation, as well as varying clinical practices in study countries, potentially introduced bias.. ClinicalTrials.gov NCT00659282.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in ASEAN type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) in the non-interventional 24-week A₁chieve study.. Indonesian, Malaysian, Filipino and Singaporean patients switched from BHI to BIAsp 30 at their physicians' discretion were included. The incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia was the primary endpoint. Changes in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), lipids, body weight and systolic blood pressure were also evaluated. Quality of life (QoL) was measured using the EQ-5D questionnaire.. For the 465 patients included (mean ± SD age: 56 ± 10.3 years, diabetes duration: 9.7 ± 7.1 years, baseline HbA1c: 9.4 ± 1.8%), the mean pre-study BHI dose was 0.62 ± 0.28 IU/kg and 63.4% were dosing BHI twice daily (bid). The mean baseline BIAsp 30 dose was 0.65 ± 0.27 U/kg, titrated up to 0.71 ± 0.28 U/kg over 24 weeks, and most patients continued bid dosing. No SADRs or major hypoglycaemic episodes were reported. The proportion of patients reporting overall hypoglycaemia decreased significantly from 10.8% at baseline to 3.4% at Week 24 (p < 0.0001). Significant improvements in glycaemic control were noted (HbA1c: -1.4 ± 1.7%, FPG: -56.7 ± 72.5 mg/dL, post-breakfast PPPG: -84.8 ± 82.8 mg/dL, p < 0.001). Mean QoL improved by +6.6 ± 14.6 points (p < 0.001).. BIAsp 30 was well-tolerated and significantly increased glycaemic control in this ASEAN subgroup poorly controlled on BHI.

Topics: Aged; Asia, Southeastern; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in the ASEAN cohort of the A₁chieve study.. Type 2 diabetes patients from Indonesia, Malaysia, Philippines and Singapore prescribed BIAsp 30 therapy were included. The primary outcome was evaluation of serious adverse drug reactions including major hypoglycaemia over 24 weeks. Secondary outcomes were changes in hypoglycaemic events, serious adverse events (SAEs) and effectiveness parameters.. This sub-analysis included 2798 patients (insulin-naive, 1903; insulin-experienced, 895) with mean age ± SD, 55.3 ± 10.8 years, BMI, 24.9 ± 4.6 kg/m(2) and diabetes duration, 7.5 ± 5.9 years. Baseline HbA1c in the entire cohort was poor (9.9%, 85 mmol/mol). A total of 15 SAEs were reported in 7 insulin-experienced patients (1 moderate event was related to BIAsp 30). Overall hypoglycaemia at Week 24 was 0.88 events/patient-year compared to 1.71 events/patient-year reported at baseline (change in proportion of patients affected, p < 0.0001). No major hypoglycaemia was reported at Week 24. BIAsp 30 significantly improved glucose control (HbA1c, fasting plasma glucose and postprandial plasma glucose, p < 0.001) at Week 24. The proportion of patients achieving HbA1c <7.0% at Week 24 was 35.3% compared to 3.5% at baseline. The lipid profile and systolic blood pressure also improved significantly (p < 0.001). Quality of life was positively impacted (mean change in visual analogue scores from EQ-5D = 10.6 ± 13.8 points, p < 0.001).. BIAsp 30 was well-tolerated and improved glucose control while decreasing the risk of hypoglycaemia.

Topics: Adult; Aged; Asia, Southeastern; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) therapy in Bangladeshi type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) as a sub-analysis of the A₁chieve study.. Bangladeshi patients switched from BHI to BIAsp 30 at the discretion of their physicians were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary outcomes comprised changes from baseline to Week 24 in the number of hypoglycaemic events, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), systolic blood pressure and body weight. Quality of life (QoL) was evaluated at baseline and Week 24 using the EQ-5D questionnaire.. A total of 82 patients (mean age ± SD: 52.3 ± 12.2 years; body mass index: 25.6 ± 3.3 kg/m(2)) with a mean diabetes duration of 9.5 ± 5.5 years and mean duration on insulin of 2.5 ± 2.4 years were included. The mean BIAsp 30 dose was 0.49 ± 0.20 U/kg at baseline and 0.47 ± 0.17 U/kg at Week 24. No SADRs were reported. No events of hypoglycaemia (overall, major, minor or nocturnal) were reported at Week 24. Mean HbA1c, FPG and PPPG levels improved by -2.5 ± 1.3%, -65.0 ± 31.8 mg/dL and -119.3 ± 48.7 mg/dL, respectively, over 24 weeks. QoL also improved (mean change from baseline: +28.5 ± 12.9 points).. Switching from BHI to BIAsp 30 therapy improved blood glucose control and was well-tolerated in this Bangladeshi subgroup.

Topics: Adult; Asian People; Bangladesh; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Prospective Studies; Quality of Life; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Indonesian type 2 diabetes patients switched from biphasic human insulin 30 (BHI 30) as a sub-analysis of the A₁chieve study.. Clinical safety and effectiveness over 24 weeks was evaluated in Indonesian patients who switched from BHI 30 to BIAsp 30 at the discretion of their physician.. A total of 244 patients with mean age ± SD 55.6 ± 9.5 years, BMI 24.6 ± 3.8 kg/m(2), and mean diabetes duration 7.8 ± 5.7 years were included. The mean pre-study BHI 30 dose was 0.56 ± 0.25 IU/kg and the baseline BIAsp 30 dose was 0.60 ± 0.26 U/kg titrated up to 0.65 ± 0.25 U/kg by Week 24. No serious adverse drug reactions were reported throughout the study. Overall hypoglycaemia decreased from 2.18 to 0.06 events/patient-year with a significant decrease in the proportion of patients affected (p < 0.0001). No nocturnal or major hypoglycaemia was reported at Week 24. HbA1c improved from 8.8 ± 1.2% at baseline to 7.3 ± 0.8% at Week 24. A total of 45 patients achieved HbA1c <7.0% as compared to 5 patients with HbA1c <7.0% at baseline. FPG and PPPG improved significantly after 24 weeks (p < 0.001). Quality of life was positively impacted (change in visual analogue scores, 3.0 ± 11.6 points, p < 0.001).. Switching from BHI 30 to BIAsp 30 in this Indonesian cohort was well-tolerated and improved glycaemic control with a decreased risk of hypoglycaemia.

Topics: Aged; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Indonesia; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Filipino patients with type 2 diabetes previously treated with biphasic human insulin 30 (BHI 30).. Safety and effectiveness outcomes were measured in all patients switching from BHI 30 to BIAsp 30 in the Filipino cohort of the 24-week, multinational, prospective, non-interventional A₁chieve study.. A total of 111 Filipino patients (mean age ± SD, 57.4 ± 12.8 years; BMI, 25.8 ± 5.6 kg/m(2)) with mean diabetes duration of 9.9 ± 7.1 years switched therapy from BHI 30 to BIAsp 30. The mean pre-study BHI 30 dose was 0.65 ± 0.28 IU/kg and the baseline BIAsp 30 dose was 0.65 ± 0.26 U/kg titrated up to 0.70 ± 0.26 U/kg by Week 24. No serious adverse drug reactions were reported. Overall hypoglycaemia was reduced from 5.62 to 1.98 events/patient-year. Minor and nocturnal hypoglycaemia decreased and no major hypoglycaemia was reported at Week 24. Glucose control improved from baseline to Week 24 (HbA1c, -2.2 ± 2.1% [24 ± 23 mmol/mol]; FPG, -72.0 ± 71.8 mg/dL; PPPG, -145.5 ± 125.4 mg/dL). A total of 24 patients achieved HbA1c levels <7.0% at Week 24 compared to 6 patients reporting this target at baseline. Quality of life was positively impacted at Week 24 (change in visual analogue scores, 15.3 ± 16.9 points).. Switching from BHI 30 to BIAsp 30 improved glycaemic control without increasing the risk of hypoglycaemia.

Topics: Aged; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Philippines; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Indonesian patients with type 2 diabetes (T2D) as part of the 24-week, international, prospective, non-interventional A₁chieve study.. Indonesian patients who started BIAsp 30 were included. Safety and efficacy was measured as part of routine clinical practice at baseline, Week 12 and Week 24.. Overall, 1324 patients having a mean ± SD age, duration of diabetes and body mass index of 55.2 ± 9.9 yrs, 6.8 ± 5.2 yrs and 24.1 ± 3.6 kg/m(2), respectively, were enrolled. 67% of patients were insulin-naive and 33% were prior insulin users. Glycaemic control was poor at baseline. After 24 weeks, significant reductions from baseline were observed in the mean glycated haemoglobin A1c (HbA1c) (-2.6%), fasting plasma glucose (-93.8 mg/dL) and postprandial plasma glucose (-134.8 mg/dL) levels in the entire cohort (p < 0.001). Significant reductions were also seen in insulin-naive patients and prior insulin users. At Week 24, 29.9% of patients in the entire cohort achieved target HbA1c level of <7.0%, while 26.7% and 39.2% achieved this target among insulin-naive patients and prior insulin users, respectively. The proportion of patients reporting overall hypoglycaemia significantly decreased in the entire cohort after 24 weeks of BIAsp 30 therapy. A small significant increase in body weight was noted in the entire cohort, insulin-naive patients and prior insulin users.. The current study suggests that BIAsp 30 can be considered as a safe and effective option for initiating as well as intensifying insulin therapy in Indonesian patients with T2D.

Topics: Adult; Aged; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Indonesia; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Prospective Studies; Quality of Life; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

The Somogyi effect postulates that nocturnal hypoglycaemia causes fasting hyperglycaemia attributable to counter-regulatory hormone release. Although most published evidence has failed to support this hypothesis, this concept remains firmly embedded in clinical practice and often prevents patients and professionals from optimizing overnight insulin. Previous observational data found lower fasting glucose was associated with nocturnal hypoglycaemia, but did not assess the probability of infrequent individual episodes of rebound hypoglycaemia. We analysed continuous glucose monitoring data to explore its prevalence.. We analysed data from 89 patients with Type 1 diabetes who participated in the UK Hypoglycaemia study. We compared fasting capillary glucose following nights with and without nocturnal hypoglycaemia (sensor glucose < 3.5 mmol/l).. Fasting capillary blood glucose was lower after nights with hypoglycaemia than without [5.5 (3.0) vs. 14.5 (4.5) mmol/l, P < 0.0001], and was lower on nights with more severe nocturnal hypoglycaemia [5.5 (3.0) vs. 8.2 (2.3) mmol/l; P = 0.018 on nights with nadir sensor glucose of < 2.2 mmol/l vs. 3.5 mmol/l]. There were only two instances of fasting capillary blood glucose > 10 mmol/l after nocturnal hypoglycaemia, both after likely treatment of the episode. When fasting capillary blood glucose is < 5 mmol/l, there was evidence of nocturnal hypoglycaemia on 94% of nights.. Our data indicate that, in clinical practice, the Somogyi effect is rare. Fasting capillary blood glucose ≤ 5 mmol/l appears an important indicator of preceding silent nocturnal hypoglycaemia.

Topics: Adult; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Circadian Rhythm; Cohort Studies; Diabetes Mellitus, Type 1; Drug Monitoring; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Monitoring, Ambulatory; Prevalence; Severity of Illness Index; United Kingdom

Topics: Diabetes Mellitus, Type 1; Humans; Hypersensitivity; Hypoglycemia; Insulin; Insulin, Isophane; Male; Middle Aged

To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Algerian patients with type 2 diabetes initiating insulin or switching from prior insulin therapy.. Insulin-naive and insulin-experienced patients, including prior basal insulin users, starting BIAsp 30 were evaluated in this sub-analysis of the 24-week, open-label, non-interventional A₁chieve study. Clinical safety and effectiveness was evaluated as a part of routine clinical care.. A total of 134 insulin-naive patients initiating BIAsp 30 at a mean dose of 0.44 ± 0.23 U/kg and 283 insulin-experienced patients, including 129 prior basal insulin users, switching from a mean pre-study insulin dose of 0.51 ± 0.23 U/kg to BIAsp 30 (0.54 ± 0.20 U/kg) were evaluated. At Week 24, the average BIAsp 30 dose was 0.60 ± 0.25 U/kg and 0.66 ± 0.24 U/kg in insulin-naive and insulin-experienced patients, respectively. No serious adverse drug reactions were reported. From baseline to Week 24, the proportion of patients experiencing overall hypoglycaemia increased in the insulin-naive group (p = 0.0067) and no significant changes were reported in the insulin-experienced group including prior basal insulin users. Glucose control improved significantly in the insulin-experienced group (p < 0.001) and appeared to improve in the insulin-naive patients and prior basal insulin users as well. Body weight increased significantly in all patients (p < 0.001). Quality of life was positively impacted after 24 weeks of BIAsp 30 therapy.. Initiating or switching to BIAsp 30 therapy in this Algerian cohort was well-tolerated and significantly improved glucose control.

Topics: Algeria; Biomarkers; Biphasic Insulins; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Quality of Life; Risk Factors; Treatment Outcome; Weight Gain

To examine the criteria that may influence physicians' choice of starting insulin in type 2 diabetes patients in routine practice in Algeria as a sub-analysis of the A₁chieve study.. A₁chieve was a 24-week international, prospective, non-interventional study conducted to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30), insulin detemir (IDet), or insulin aspart alone or in combination, in real-life clinical settings. We report an analysis of baseline data from insulin-naive patients initiating basal or premix insulin from the Algeria cohort (n = 1494). Demographic and anthropometric data, blood glucose control at inclusion, microvascular complications, and pre-study therapy was compared between the two groups.. A total of 772 insulin-naive patients initiating therapy with IDet or BIAsp 30 were included in this analysis: IDet: 638 (83%), BIAsp 30: 134 (17%). Most IDet-group patients initiated once-daily therapy (n = 636; 99.7%); conversely, most BIAsp 30-group patients started twice-daily therapy (n = 104; 77.6%). Baseline factors influencing regimen choice were microvascular complications (odds ratio [95% CI], yes/no: 0.73 [0.55, 0.98]; p = 0.034) and HbA1c at baseline (%, odds ratio [95% CI] 0.82 [0.72, 0.94]; p = 0.004).. In routine practice, physicians in Algeria are more likely to prescribe basal insulin at initiation of insulin therapy in type 2 diabetes. The prescription of a premix insulin therapy correlated with poor glycaemic control and the incidence of microvascular complications.

Topics: Algeria; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Practice Patterns, Physicians'; Prospective Studies; Treatment Outcome

Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study.. Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables.. The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6-32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5-17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9-55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI -10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2-42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1-25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine.. There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice.

Topics: Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Coma; Female; Finland; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Medical Record Linkage; Poisson Distribution; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk

The intent of this study was to evaluate the efficacy and safety of transitioning from a continuous intravenous (IV) regular human insulin (RHI) or intermittent IV RHI therapy to subcutaneous neutral protamine Hagedorn (NPH) insulin with intermittent corrective IV RHI for critically ill patients receiving continuous enteral nutrition (EN).. Data were obtained from critically ill trauma patients receiving continuous EN during transitional NPH insulin therapy. Target blood glucose concentration (BG) range was 70-149 mg/dL. BG was determined every 1-4 hours.. Thirty-two patients were transitioned from a continuous IV RHI infusion (CIT) to NPH with intermittent corrective IV RHI therapy. Thirty-four patients had NPH added to their preexisting supplemental intermittent IV RHI therapy (SIT). BG concentrations were maintained in the target range for 18 ± 3 and 15 ± 4 h/d for the CIT and SIT groups, respectively (P < .05). Thirty-eight percent of patients experienced a BG <60 mg/dL, and 9% had a BG <40 mg/dL. Hypoglycemia was more prevalent for those who were older (P < .01) or exhibited greater daily BG variability (P < .01) or worse HgbA1C (p < 0.05).. Transitional NPH therapy with intermittent corrective IV RHI was effective for achieving BG concentrations within 70-149 mg/dL for the majority of the day. NPH therapy should be implemented with caution for those who are older, have erratic daily BG control, or have poor preadmission glycemic control.

Topics: Administration, Intravenous; Adult; Aged; Blood Glucose; Critical Illness; Drug Administration Schedule; Enteral Nutrition; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

Type 2 diabetes mellitus is characterized by hyperglycaemia. Incidence and progression of microvascular complications have been shown to undergo reduction with lowered glucose levels.. This is an open-label, non-randomized, non-interventional, observational study of safety and efficacy of BiAsp 30, enrolling 2223 patients with type 2 diabetes mellitus. Patients previously treated with oral antidiabetic drugs and/or human insulin were recruited, provided they had been hospitalized for at least 3 days. Data were collected during a single multi-stage visit lasting up to 6 days, during the patient's hospitalization period. A mild hypoglycaemic episode was defined as blood glucose measurement < 56 mg/dL (3.1 mmol/L). A severe hypoglycaemia was hypoglycaemic episode requiring assistance of another person.. The total number of hypoglycaemic episodes decreased over time of follow-up. The intensity of severe hypoglycaemic episodes decreased by almost a third from day to day (IRR = 0.64, 95%, p < 0.001). However, intensity of mild hypoglycaemic episodes was the same over the subsequent days of follow-up (IRR = 0.97, p > 0.1). Mean blood glucose concentration decreased from 202.0 mg/dL to 157.8 mg/dL after 3 days and to 138.3 mg/dL after 6 days (p < 0.001).. This study highlights the safety, efficacy and ease of initiation of insulin BiAsp 30 therapy for treatment of type 2 diabetes mellitus.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Treatment Outcome

There are an estimated 1000 children with diabetes in Tanzania. Recently, the first two pediatric endocrinologists, trained in the European Society for Paediatric Endocrinology (ESPE)/International Society for Paediatric and Adolescent Diabetes (ISPAD) program in Nairobi, Kenya, entered practice. The purpose of this study was to prospectively assess the impact of a 6-month diabetes management and education program on glycemic control and acute complications in children and adolescents in Tanzania.. Eighty-one patients aged 3-19 yr were enrolled. All were on split-dose Insulatard (Neutral Protamine Hagedorn) and Actrapid (soluble, regular) insulin, and were given three glucose test strips per week. Children were seen in clinic an average of six times over 6 months and received 3 h of diabetes education. A structured questionnaire evaluated social demographic data and acute complications.. Despite regular clinic attendance, diabetes education, and provision of insulin, hemoglobin A1c (HbA1c) levels did not improve. Four children (5%) had HbA1c 7.5%, 22 (28%) HbA1c 7.5-10%, 9 (24%) HbA1c 11-12.5%, and 36 (44%) HbA1c >12.5%. There was a substantial reduction in severe hypoglycemia, with 17% of subjects experiencing this acute complication compared to 52% in the 6 months prior to study enrolment. Six children were admitted in diabetic ketoacidosis during the study compared to three during the previous 6 months. Twenty-six children (36%) reported missing >6 doses of insulin (but only two lacked insulin).. Diabetes education significantly reduced the risk of severe hypoglycemia, but better glycemic control of diabetes was not attained. Further study is needed to explore factors to improve glycemic control including increased testing, or perhaps different insulin regimens.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Therapy, Combination; Family; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin, Isophane; Insulin, Regular, Human; Insulin, Regular, Pork; Isophane Insulin, Human; Male; Medication Adherence; Outpatient Clinics, Hospital; Patient Education as Topic; Prospective Studies; Tanzania

To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands.. A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€).. Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12,644 (Denmark), € 12,612 (Sweden), € 16,568 (Finland) and € 12,216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin.. Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings.

Topics: Cost-Benefit Analysis; Denmark; Diabetes Mellitus, Type 1; Female; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Netherlands; Pharmacies; Quality-Adjusted Life Years; Sweden

We evaluated the effectiveness of insulin glargine (glargine)-based regimens in patients with type 2 diabetes mellitus (T2DM) in clinical practice in Spain.. This was a retrospective, registry-based study of 1482 patients treated with neutral protamine Hagedorn (NPH) who were either switched to glargine or maintained on NPH at investigators' discretion. The primary outcomes were HbA(1c) change over a period of 4-9 months follow-up and incidence of hypoglycaemia.. Prior to switching treatment, mean ± standard deviation HbA(1c) was worse in the glargine vs. the NPH group (8.3 ± 1.2% vs. 7.9 ± 1.1% respectively; p < 0.0001). After 4-9 months of treatment, mean reductions in HbA(1c) were greater with glargine vs. NPH (-1.0 ± 1.0% vs. -0.2 ± 0.8% respectively; p < 0.0001) and the incidence of hypoglycaemia in the month prior to the study visit was lower (21.8% vs. 47.6% respectively; p < 0.0001). An expected reduction in dosing frequency, as well as in the basal insulin dose was reported for glargine vs. NPH, with 97.3% of glargine-treated patients on once-daily injections and 81.2% on NPH receiving twice-daily therapy. Improvements in treatment satisfaction were significantly higher with glargine (p < 0.0001).. In a Spanish clinical practice setting, patients with T2DM who switched to glargine from NPH experienced significantly greater reductions in mean HbA(1c) and a lower incidence of hypoglycaemia than patients maintained on NPH.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

Glycaemic control is critical to prevent diabetic complications and mortality. This 6-month, open-label, observational study assessed the efficacy and safety of switching Japanese patients with type 2 diabetes from neutral protamine Hagedorn (NPH) insulin to insulin detemir.. Patients with type 2 diabetes (n = 126) receiving basal-bolus insulin therapy with NPH insulin plus rapid-acting insulin analogues were recruited. NPH insulin was replaced with insulin detemir for 6 months. Glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), daily glucose levels and hypoglycaemia were monitored. Nocturnal quality of life was assessed by insulin therapy related quality of life at night questionnaire.. HbA(1c), FPG and body weight were all significantly reduced after treatment with insulin detemir for 6 months, without increasing severe hypoglycaemia. Insulin dose increased significantly over the same time. There were significant improvements in overall nocturnal quality of life, as well as well-being.. Treatment with insulin detemir for 6 months resulted in substantial benefits, including reduced HbA(1c), FPG and body weight, and improvements in nocturnal quality of life, without increasing hypoglycaemia.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Japan; Male; Middle Aged; Quality of Life; Surveys and Questionnaires

To evaluate treatment satisfaction before and after starting biphasic insulin aspart 30 (BIAsp 30) therapy in patients with type 2 diabetes mellitus (T2D) in the IMPROVE study Japan using the Diabetes Medication Satisfaction (DiabMedSat) questionnaire.. The DiabMedSat questionnaire assesses overall satisfaction with drug therapy for diabetes treatment in three domains: burden, efficacy and symptoms. Patients previously treated by oral anti-diabetic drugs in the IMPROVE study Japan answered the DiabMedSat questionnaires at baseline (week 0) and week 26 after starting BIAsp 30 treatment.. The mean scores for each domain at weeks 0 and 26, respectively, were: burden, 64.5 and 67.5 (p = 0.041); efficacy, 55.0 and 61.5 (p < 0.001); and symptoms, 70.9 and 68.1 (p = 0.049). The overall scores were 63.4 and 65.6, respectively (p = 0.079). With regard to burden, bothersome aspects were significantly improved with BIAsp 30 treatment at week 26, compared with treatment with oral anti-diabetic drugs at week 0. Major hypoglycemic episodes were very rare; most hypoglycemic events were minor and occurred during the daytime.. The study results indicate that BIAsp 30 does not adversely affect QOL in Japanese patients at insulin initiation.

Topics: Aged; Algorithms; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Japan; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Time Factors

The objective of this study was to evaluate the short-term and long-term clinical and economic outcomes associated with insulin glargine or NPH insulin in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with oral anti-diabetic drugs in Switzerland, modeling the interaction between hypoglycemia and glycemic control (HbA1c).. A validated discrete event simulation model for T2DM was used to predict incidence of short-term complications (symptomatic, nocturnal and severe hypoglycemic events) and long-term complications (microvascular and macrovascular events), life expectancy, quality-adjusted life years (QALYs) and direct medical costs in patients treated with insulin glargine or NPH insulin. The model was populated with published Swiss patient characteristics with T2DM. Baseline risks of hypoglycemic events, utility decrements of diabetes-related long-term complications and the hypoglycemia fear score were derived from the literature. Relative risk reductions of hypoglycemia adjusted for HbA1c using insulin glargine compared with NPH insulin were based on a published negative binomial meta-regression analysis. Costs of severe hypoglycemia, micro- and macrovascular events were analyzed from literature whenever possible otherwise guideline-projected resource-use estimations were valued with Swiss official prices or tariffs in 2006 CHF. Simulations were run with 1,000 patients per cohort over a time horizon of 40 years. Incremental cost effectiveness ratios (ICERs) were presented as cost per QALY and per life year gained (LYG). Future costs and clinical benefits were discounted at 3.5%. Wide-range one-way sensitivity analyses were performed.. Insulin glargine was associated with an improvement in quality of life (0.098 QALYs per patient) and additional life expectancy (0.05 life years gained per patient) compared to NPH insulin. Incremental costs of CHF 2,578 resulted in an ICER of CHF 26,271 per QALY and CHF 51,100 per LYG. The cost per QALY was most sensitive to changes in costs, utility decrements and relative risk reductions of hypoglycemia.. This study evaluated, for the first time, the cost effectiveness of insulin glargine versus NPH insulin for the treatment of T2DM considering the interaction between glycemic control and hypoglycemia in Switzerland. The base case and sensitivity analyses demonstrated that insulin glargine proved to be cost-effective with respect to accepted willingness to pay thresholds and therefore represents good value for money.

Topics: Aged; Computer Simulation; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Switzerland; Time Factors; Treatment Outcome

To assess the safety and efficacy of insulin analogues versus human insulin in pregnant women with pregestational diabetes.. We collected data on pregnant women with type 1 or type 2 diabetes who were attended at the Diabetes and Pregnancy Unit between January 1998 and April 2008 (N=351). Two hundred and forty one patients were treated with regular insulin and NPH and 110 were treated with different combinations of insulins including an insulin analogue (most of them with NPH and lispro).. There was no significant difference in terms of congenital malformation rate between groups (3.3% and 3.6%). The group on insulin analogue had slightly higher mean HbA1c during the first trimester than the group on human insulin (6.6 [1.0]% vs 6.9 [1.1]%; P=0,022) and needed smaller insulin doses during whole pregnancy. Severe hypoglycaemia was significantly less frequent among women treated with a rapid insulin analogue (2.3 vs 10.0%; P=0,025). Neonatal hypoglycaemia was significantly more frequent in the group treated with a rapid insulin analogue (34.9 vs 23.6%; P=0.043) due to the concomitant use of an insulin pump. Other obstetric and neonatal variables were not different between the two groups.. Our study shows that insulin analogues are safe during pregnancy in women with pregestational diabetes mellitus. Overall, glycaemic control, maternal and foetal outcome were similar to those with human insulin. The main advantage with respect to human insulin was to importantly reduce maternal severe hypoglycaemia.

Topics: Abnormalities, Drug-Induced; Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Insulin, Regular, Human; Logistic Models; Pregnancy; Pregnancy in Diabetics; Retrospective Studies

Premixed, or biphasic, insulins containing varying proportions of rapid- and intermediate-acting insulin components have been developed to limit the number of daily injections for patients who require both prandial and basal insulin injections.. This study was conducted to determine whether there were differences in glycosylated hemoglobin (HbA(1c)), weight change, hypoglycemia occurrence, and treatment discontinuation between patients treated with biphasic insulin aspart 30 (BIAsp-30) or biphasic human insulin 30 (BHI-30) in UK general practice.. Data were from >350 general practices from the United Kingdom. Patients were stratified by treatment regimen, diabetes type, and insulin status (naive or experienced). Changes in HbA(1c) and weight were compared from baseline (the date of the first prescription for either insulin) through 180 days of follow-up using ANCOVA. Hypoglycemia incidence rate ratios were compared, and the adjusted likelihood of hypoglycemia was evaluated by logistic regression. Rates of treatment discontinuation were compared using the Cox proportional hazards model.. The study included data from 7720 patients, of whom 1333 (17.3%) had type 1 diabetes and 4457 (57.7%) were male. Patients' mean (SD) age was 57.9 (19.8) years, and their mean body mass index was 29.5 (6.2) kg/m(2). The difference in HbA(1c) reduction was significant for BIAsp-30 compared with BHI-30 in insulin-naive patients with type 1 diabetes (0.57%; P = 0.045), insulin-naive patients with type 2 diabetes (-0.17%; P = 0.003), and insulin-experienced patients with type 2 diabetes (-0.23%; P = 0.007). The difference between insulins was not significant in insulin-experienced patients with type 1 diabetes. Five hundred ninety-four patients (7.7%) experienced at least one hypoglycemic event. The incidence rate ratio for reported hypoglycemia was significantly lower with BIAsp-30 compared with BHI-30 in insulin-naive patients with type 2 diabetes (0.74; 95% CI, 0.62-0.89; P = 0.001); the difference between insulins was not significant in the other groups. The adjusted hazard ratio for treatment discontinuation was significant for BIAsp-30 versus BHI-30 in insulin-experienced patients with type 2 diabetes (0.693; 95% CI, 0.543-0.884; P = 0.003), whereas the hazard ratios for the other groups did not reach statistical significance. There were no significant differences in weight change between BIAsp-30 and BHI-30 in any of the groups.. In this analysis, BIAsp-30 was associated with improved glycemic control (HbA(1c)) compared with BHI-30 in insulin-naive patients with type 1 or type 2 diabetes and insulin-experienced patients with type 2 diabetes. BIAsp-30 was associated with reduced hypoglycemia in insulin-naive patients with type 2 diabetes and lower rates of treatment discontinuation in insulin-experienced patients with type 2 diabetes. Cambridgeshire Research Ethics Committee: REC 08/H0305/47.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Biphasic Insulins; Body Weight; Child; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United Kingdom; Young Adult

To compare 2-year glycaemic control, hypoglycaemia and healthcare expenditures following insulin glargine (glargine, n = 2105) or neutral protamine Hagedorn (NPH) insulin (NPH, n = 734) initiation in patients with type 2 diabetes (T2D).. Retrospective cohort study using an integrated US health insurance administrative database was conducted. Individuals with a diabetes diagnostic claim and initiated basal insulin therapy with glargine or NPH from 2001 to 2005 dispensed at least one oral antidiabetic drug prescription during 6 months prior to basal insulin initiation and enrolled in the same health insurance plan from 6 months before to 12 months or more after insulin initiation were identified. Repeated measures mixed-effects models evaluated glycaemic and financial outcomes to account for factors potentially contributing to selection of insulin therapy, that is, age, gender, baseline HbA1c level, health expenditures, co-morbidities, healthcare utilization, pharmacy co-payment and follow-up antidiabetic medications.. Adjusted mean HbA1c value in the first year following insulin initiation was significantly lower for glargine versus NPH initiators (Δ = -0.43, p = 0.006); this difference diminished in the second year (Δ = -0.16, p = 0.375). First-year adjusted quarterly hypoglycaemia incidence rates were lower for glargine (2.1%) versus NPH (2.4%) (p = 0.02) as was the second-year quarterly rate (1.8 vs. 2.2%; p = 0.01). Both the first- and second-year adjusted total healthcare expenditures were lower in the glargine versus NPH group (year 1: $18,720 vs. $19,996, p = 0.005; year 2: $15,008 vs. $17,336; p < 0.001).. Glargine therapy may be an effective long-term option for improving glycaemic control, with lower rates of hypoglycaemia and healthcare costs in patients with T2D.

Topics: Blood Glucose; Cohort Studies; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States

Despite a wealth of clinical trial data supporting use of the premixed insulin analogue, biphasic insulin aspart 30 (BIAsp 30) in the treatment of type 2 diabetes mellitus (T2DM), there is limited documentation of its use in primary care-based clinical practice.. An observational study investigating the safety and efficacy of BIAsp 30 in routine clinical practice was conducted. Patients were followed up 3 and 6 months after initiating insulin treatment. Safety and efficacy measures were documented.. During the course of the study, 1154 patients were included (age range 20-95 years), of whom 89% completed the 6-month follow-up period. Mean HbA(1c) at baseline was 8.8% (73mmol/mol), and had improved to 7.2% (55mmol/mol) after 6 months of treatment. The rate of total hypoglycaemia at completion of the study was 4.1 events per patient year. Major hypoglycaemic events were rare (two in total).. BIAsp 30 was initiated safely and effectively in insulin-naïve patients with T2DM. The safety and efficacy profile observed in clinical trials was confirmed in this largely primary care-based setting in Sweden.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Health Services Research; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Primary Health Care; Prospective Studies; Sweden; Time Factors; Treatment Outcome; Young Adult

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin, Isophane; Insulin, Long-Acting; Patient Acceptance of Health Care; Weight Gain

Topics: Blood Glucose; Clinical Trials as Topic; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

To compare total costs and risk of hypoglycemia in patients with type 2 diabetes (T2D) initiated on NPH insulin versus glargine in a real-world setting.. This study used claims data (10/2001 to 06/2005) from a privately insured U.S. population of adult T2D patients who were initiated on NPH or glargine following a 6-month insulin-free period. A sample of 1698 glargine-treated and 400 NPH-treated patients met the inclusion criteria. Total and diabetes-related costs (inflation-adjusted to 2006) were calculated for 6-month pre- and post-index periods and compared between 400 patient pairs matched by a propensity score method.. In the post-index 6-month period, glargine patients incurred higher diabetes-related drug costs than NPH patients ($785 versus $632, p<0.0001) but there were no significant differences in diabetes-related medical or total costs, or all other total cost categories. Compared to the pre-index period, glargine patient costs declined by $2420 (p=0.058) whereas NPH patient costs declined by $4200 (p=0.046), with no statistically significant group differences (p=0.469). Among patients with hypoglycemia-related claims (0.75% in both groups), mean hypoglycemia-related costs were $85 and $202 for NPH and glargine patients, respectively (p=0.564).. Initiation of either NPH or glargine was associated with major cost reductions and infrequent hypoglycemia-related claims.

Topics: Adult; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Therapy; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Selection; Probability; Propensity Score; Retrospective Studies; United States

Insulin and corticosterone signal energy surfeit and deficiency, respectively, to metabolic structures in the brain, including the hypothalamic arcuate nucleus (ARH). This peripheral input may be subject to ovarian control, since ovariectomy (OVX) increases insulin receptor transcripts and decreases glucocorticoid receptor protein in the hypothalamus. The present studies examined the hypothesis that estradiol regulates basal and hypoglycemic patterns of ARH insulin and glucocorticoid receptor mRNA expression, and governs habituation of these gene profiles to recurring intermediate insulin administration. The premise that estrogen receptor-alpha (ERalpha) and beta (ERbeta) gene profiles may be regulated differentially during acute and chronic hypoglycemia in the presence of estradiol was also evaluated. Insulin receptor-beta chain (InsRb), type-II glucocorticoid receptor (GR), ERalpha, and ERbeta mRNA levels in ARH tissue microdissected from estradiol benzoate (EB)- and oil-implanted OVX rats after single or serial sc neutral protamine Hagedorn insulin (NPH) injection were measured by quantitative real-time RT-PCR. ARH InsRb gene profiles were decreased, relative to baseline, after either one or four NPH injections in OVX + EB rats; mean mRNA levels were significantly lower after serial dosing since basal InsRb transcripts were diminished by precedent NPH treatment. InsRb transcription rates did not differ among OVX + oil treatment groups. Acute insulin elevated ARH GR mRNA relative to baseline in both EB- and oil-implanted rats. Prior NPH injections increased basal GR gene expression and suppressed transcriptional reactivity to a fourth dose of NPH in OVX + EB, but not OVX + oil animals. ARH ERalpha and ERbeta mRNA levels were increased or decreased, respectively, after one insulin dose in OVX + EB rats. Baseline expression of these genes was correspondingly augmented or suppressed after precedent NPH treatment, but ERalpha and ERbeta transcripts were not modified relative to these adjusted baselines after a fourth NPH dose. In the presence of estradiol, ARH InsRb and GR gene profiles exhibit divergent modifications during acute NPH-induced hypoglycemia, as well as opposite adjustments in baseline expression after serial NPH dosing. GR transcriptional acclimation to recurring NPH administration was also estrogen-dependent. Further research is needed to characterize potential effects of adjustments in ARH neuronal sensitivity to insulin and corticosterone

Topics: Animals; Arcuate Nucleus of Hypothalamus; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Profiling; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Ovariectomy; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Receptors, Glucocorticoid; RNA, Messenger

It has been reported that adrenalectomy (ADX) and the potent type II glucocorticoid receptor agonist, dexamethasone, exert opposing effects on glucose utilization in specific brain regions, including the hypothalamus. The present study investigated the hypothesis that ADX alters neuronal substrate fuel transporter mRNA levels in characterized hypothalamic and hindbrain metabolic monitoring structures, and adjustments in these gene profiles are correlated with modified transcription of genes encoding the glucose sensor, glucokinase (GCK), and the energy-dependent, inwardly-rectifying potassium channel, K(ATP). The lateral hypothalamic area (LHA), ventromedial hypothalamic nucleus (VMN), and dorsal vagal complex (DVC) were microdissected from ADX and sham-operated male rats 2 h after neutral protamine Hagedorn insulin or vehicle injection, and evaluated by quantitative real-time RT-PCR for neuronal glucose (GLUT3, GLUT4), monocarboxylate (MCT2) transporter, GCK, and sulfonylurea receptor-1 (SUR1) mRNA content. ADX modified basal fuel transporter and energy transducer gene expression in a site-specific manner since this manipulation decreased MCT2 and GLUT3 transcription in the DVC only; increased or decreased GCK mRNA in the LHA and VMN, respectively; and decreased SUR1 gene profiles in the DVC and LHA. Adrenal removal did not alter baseline GLUT4 mRNA in any structure examined. ADX also prevented the following transcriptional responses to insulin-induced hypoglycemia: downregulated DVC MCT2, downregulated DVC and upregulated LHA and VMN GLUT3, upregulated LHA GLUT4, upregulated LHA GCK, and upregulated VMN SUR1. These results show that the adrenals regulate basal GLUT3 gene profiles in the DVC alone; during hypoglycemia, these glands suppress (DVC) or increase GLUT3 (LHA and VMH) mRNA, and selectively elevate GLUT4 transcripts in the LHA. The data demonstrate divergent adrenal control of DVC neuronal monocarboxylate transporter gene expression under basal (stimulatory) versus hypoglycemic (inhibitory) conditions. The current work also reveals contrasting adrenal regulation of baseline GCK mRNA in the LHA (inhibitory) and VMN (stimulatory), as well as adrenal-dependent hypoglycemic enhancement of LHA GCK and VMN SUR1 gene profiles. Additional research is required to characterize the impact of adrenal-sensitive substrate transporter and metabolic transducer function on fuel uptake and metabolic regulatory signaling in these brain sites.

Topics: Adrenal Glands; Adrenalectomy; Animals; ATP-Binding Cassette Transporters; Gene Expression Regulation; Glucokinase; Glucose Transporter Type 3; Glucose Transporter Type 4; Hypoglycemia; Hypothalamus; Insulin, Isophane; Male; Monocarboxylic Acid Transporters; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; Receptors, Drug; Rhombencephalon; RNA, Messenger; Sulfonylurea Receptors; Transcription, Genetic

Topics: Diabetes Mellitus, Type 2; Eating; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Middle Aged; Taraxacum

Arcuate neuropeptide Y (NPY)/agouti-related pepide (AgRP) neurones regulate energy homeostasis, and express the putative glucosensor, glucokinase (GCK). The present study performed multi-transcriptional profiling of these neurones to characterise NPY, AgRP and GCK gene expression during intermediate insulin-induced hypoglycaemia, and to determine whether these transcriptional responses acclimate to repeated insulin dosing. We also examined whether these neurones express insulin, glucocorticoid and oestrogen receptor gene transcripts, and whether the levels of these receptor mRNAs are modified by insulin-induced hypoglycaemia. Individual NPY-immunoreactive neurones were laser-microdissected from the caudal arcuate nucleus after single or serial dosing with neutral protamine Hagedorn insulin (NPH), and evaluated by quantitative real-time reverse transcriptase-polymerase chain reaction for the assessment of neurotransmitter and receptor gene expression. Mean NPY and AgRP mRNA in harvested NPY neurones was unchanged or augmented, respectively, by one NPH dose, although repeated NPH administration up-regulated NPY, whereas AgRP gene transcripts were down-regulated. NPH elicited divergent modifications in the ERalpha and ERbeta mRNA content of sampled neurones. ERalpha transcripts were amplified by both acute and chronic NPH-induced hypoglycaemia, whereas ERbeta gene expression was unaltered during a single bout, but suppressed during recurring hypoglycaemia. Glucocorticoid receptor (GR) mRNA levels were increased by a single insulin dose, but unaffected by serial NPH dosing. Insulin receptor-beta chain (InsRb) gene transcripts were insensitive to acute NPH-induced hypoglycaemia, but repeated NPH inhibited this gene transcript. Neither acute nor recurring hypoglycaemia modified GCK mRNA levels in caudal hypothalamic arcuate nucleus (ARH) NPY/AgRP neurones, but baseline GCK transcription was suppressed by the latter. This evidence for the habituation of hypoglycaemic patterns of InsRb, GR and ERbeta gene transcription to serial NPH dosing implies that such treatment may alter reactivity of caudal ARH NPY/AgRP neurones to receptor ligands, and supports the need to determine whether adaptive changes in neuronal sensitivity to insulin, corticosterone and/or oestrogen cause up- versus down-regulation of NPY and AgRP neurotransmission, respectively, by this caudal ARH subpopulation during chronic hypoglycaemia.

Topics: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Base Sequence; DNA Primers; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Hypoglycemia; Insulin, Isophane; Lasers; Neurons; Neuropeptide Y; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley

To compare hypoglycaemic events, glycated haemoglobin (HbA1c) and changes in body weight in Muslim patients with Type 2 diabetes receiving Humalog Mix 50 and human Mixtard 30 twice daily during Ramadan fasting.. Data were collected from Muslim patients with Type 2 diabetes attending primary care practices in North-West London, who were on Mixtard 30 insulin twice daily before Ramadan. Group 1 had their evening insulin changed to Humalog Mix 50 (n = 26) 2 weeks before Ramadan, i.e. taking Mixtard 30 at predawn meal and Humalog Mix 50 at the sunset meal during Ramadan. As the major proportion of the daily caloric intake was consumed at the sunset meal, the rationale of switching the evening dose from human Mixtard 30 to Humalog Mix 50 was to provide more rapid-acting insulin that has shorter time of onset and peak time for the large evening meal to improve the postprandial glucose control without increasing the risk of hypoglycaemia. Group 2 continued on Mixtard 30 twice daily (n = 26). All patients received structured education about how to identify and manage hypoglycaemia during Ramadan.. Group 1 had a mean HbA1c reduction of 0.48% (p = 0.0001) before and after Ramadan, whereas group 2 had a mean HbA1c increase of 0.28% (p = 0.007). Group 1 was associated with a small reduction of 0.04 (p = 0.81) in the mean number of hypoglycaemic events during Ramadan compared with before Ramadan, whereas group 2 was associated with an increase of 0.15 (p = 0.43), although these differences between the groups were not statistically significant following adjustment for baseline factors [LSM difference between groups = 0.135, p = 0.36, 95% confidence limits (-0.16, 0.43)].. Changing to humalog Mix 50 during Ramadan resulted in improvement in glycaemic control without increasing the incidence of hypoglycaemia.

Topics: Aged; Biphasic Insulins; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Islam; Male; Middle Aged; Risk Factors; Young Adult

Understanding treatment satisfaction (TS) for diabetes is increasingly important as treatment options increase. This study examines treatment satisfaction with NovoMix® 30 in an observational study in patients with type 2 diabetes.. The DiabMedSat assesses Overall, Treatment Burden, Symptom and Efficacy Treatment Satisfaction. The impact of type of pretreatment variables on TS was examined by ANOVA at baseline and week 26. Satisfaction at week 26 was examined by t-test and effect size. Linear regression models examined impact of prior treatment factors (age, gender, duration of diabetes, type of prior treatment and diabetes-related comorbidities) and current treatment factors (weight gain, hypoglycemic events, reaching therapeutic goal) on TS.. The data set comprised 17,488 persons. Prior treatment with insulin had a more positive impact on baseline satisfaction. At week 26, there were no differences between type of prior treatment groups in Overall, Symptoms and Burden TS. Current treatment with NovoMix 30 significantly improved TS. Regression analyses examining the combined effect of pretreatment factors and current treatment factors found that all factors except for age-impacted TS although the domains impacted varied.. Patients treated with NovoMix 30 reported improved treatment satisfaction, and the improvement is considered clinically meaningful to patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biphasic Insulins; Child; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Surveys and Questionnaires; Young Adult

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

Weight gain is a significant problem in diabetic patients in terms of worsening glycemic control, increasing diabetic and cardiovascular morbidity and mortality, and contributing to social and psychological problems. In the present study, we evaluated the effects of a biphasic analog and regular NPH insulin mixtures on weight gain in patients with Type 2 diabetes mellitus (T2DM) over 1 year.. Group I consisted of 71 patients (29 men and 42 women) being treated with analog mixtures (insulin lispro 75/25 mix and biphasic insulin aspart 70/30 mix) twice daily; Group II consisted of 69 patients (23 men and 46 women) being treated with a regular insulin mixture (70/30) twice daily. Starting weight, body mass index, HbA1c, and hypoglycemic episodes were evaluated after 6 and 12 months.. Weight gain in Group I at 6 and 12 months was 1.41 ± 2.70 and 2.08 ± 3.74 kg, respectively. In Group II, weight gain at 6 and 12 months was 1.5 ± 3.0 and 2.29 ± 3.85 kg, respectively. Intragroup comparisons indicated that, for both groups, weight gain at 6 and 12 months differed significantly from the starting weight. However, no significant differences in weight gain were found between the two groups (P > 0.05).. The weight-increasing effects of an analog mixture of insulin and the NPH regular mixture of insulin appear to be similar. This should be taken into account when determining the type of insulin to use in treating T2DM patients.

Topics: Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Weight Gain

The IMPROVE study evaluated the safety and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients in the routine practice. Here we present the results for patients from Italy.. Adverse events, hypoglycaemia, glycaemic control, patient treatment satisfaction and physician resource utilisation were assessed at baseline and 26 weeks.. Out of the 1371 patients enrolled, 84.1% (n=1153) were receiving BIAsp 30 at baseline (in accordance with local regulations), and were included in the study. Mean HlbA, reduction was--0.63% after 26 weeks (p < 0.001); 26.5% and 13.5% of patients reached the HbA(1c) targets of < 7% and < 6.5%, respectively. Fasting and postprandial blood glucose significantly decreased; 65% of patients were using BIAsp 30 once daily and 32% twice daily at final visit. Rates of major and minor hypoglycaemic events also significantly decreased. Small weight increase was observed, and total insulin daily dose increased from 0.29 IU/kg pre-study to 0.32 IU/kg at final visit.. In Italy, BIAsp 30 in the routine care improved glycaemic control and reduced hypoglycaemia; however, there was little intensification and titration. This may partly explain the relatively small improvement in glycaemic control in Italy compared with other countries in the IMPROVE study.

Topics: Aged; Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; International Cooperation; Italy; Male; Middle Aged; Patient Satisfaction

We compared maternal and neonatal outcomes in diabetic pregnancies treated with either insulin glargine or neutral protamine Hagedorn (NPH) insulin. We performed a retrospective chart review of diabetic pregnant patients using the Diabetes Care Center of Wake Forest University during the years 2000 to 2005. Outcomes of interest included maternal hemoglobin A1C, average fasting and 2-hour postprandial blood sugars, mode of delivery, birth weight, 5-minute Apgar score < 7, umbilical artery pH < 7.20, incidence of neonatal hypoglycemia, and pregnancy complications. A total of 52 diabetic pregnant patients were included in this study. Twenty-seven women used insulin glargine. A total of 13 women used insulin glargine during the first trimester. Glycemic control was similar in women who used NPH insulin and insulin glargine, as determined by hemoglobin A1C levels and mean blood sugar values. There were no differences in mode of delivery, average birth weight, or neonatal outcomes. Maternal and fetal/neonatal outcomes appear similar in pregnant diabetic women who use either NPH insulin or insulin glargine in combination with a short-acting insulin analogue to achieve adequate glycemic control during pregnancy. Insulin glargine appears to be an effective insulin analogue for use in women whose pregnancies are complicated by diabetes.

Topics: Adult; Apgar Score; Birth Weight; Blood Glucose; Carbon Dioxide; Delivery, Obstetric; Diabetes, Gestational; Eating; Fasting; Female; Gestational Age; Glycated Hemoglobin; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Oxygen; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pregnancy Outcome; Retrospective Studies; Umbilical Arteries; Young Adult

Insulin glargine (glargine) and insulin NPH (NPH) are two basal insulin treatments. This study investigated the effect on glycaemic control of switching from a NPH-based regimen to a glargine-based regimen in 701 patients with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care data.. Data for this retrospective observational study were extracted from a UK primary care database (The Health Improvement Network). Patients were required to have at least 12 months of data before and after switching from NPH to glargine. The principal analysis was the change in HbA(1c) after 12 months treatment with glargine; secondary analyses included change in weight and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable reporting of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables.. After adjustment, both diabetic cohorts showed statistically significant reductions in mean HbA(1c) 12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with baseline HbA(1c); patients with baseline HbA(1c) > or = 8% had reductions of 0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant change in weight or total daily insulin dose while on glargine. The majority of patients received a basal-bolus regimen prior to and after the switch (mean 79.3% before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%, respectively in type 2 patients, p > 0.05).. In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.

Topics: Adult; Body Weight; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Young Adult

Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts.. The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE (a large, multinational, observational) study. The children investigated were using basal-bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians.. Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7-8.9%, p < 0.001) and mean fasting glucose [185-162 mg/dL (10.3-9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged.. Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.

Topics: Adult; Blood Glucose; Child; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Tolerance; Europe; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Safety; Turkey

Activation of central type II glucocorticoid receptors (GR) during neutral protamine Hagedorn insulin (NPH) administration exacerbates recurring hypoglycemia. The hypothalamic paraventricular nucleus (PVN) integrates metabolic sensory input, controls autonomic and neuroendocrine motor outflow, and is characterized by abundant GR expression. The present studies investigated the hypothesis that PVN GR mediate intensification of hypoglycemia by serial NPH dosing, and that PVN glucokinase (GCK) and glucoregulatory neuropeptide genes acclimate to this treatment paradigm through GR-dependent mechanisms. Groups of adult male rats were injected subcutaneously with one or four doses of NPH, on as many days, while controls received vehicle. Bilateral administration of the selective GR antagonist, CP-472555, into the PVN prior to the first three NPH injections prevented amplification of hypoglycemia in response to the final insulin dose, while intra-PVN delivery of the GR agonist, dexamethasone, to euglycemic rats did not modify ensuing NPH-induced hypoglycemia. Quantitative real-time RT-PCR analysis of microdissected PVN tissue revealed that GCK, corticotropin-releasing hormone (CRH), oxytocin (OT), and vasopressin (VP) mRNA levels were unchanged in response to acute NPH, and baseline gene profiles measured 24 h after antecedent injections were similar to vehicle controls. In contrast, serial dosing with NPH elevated CRH and GCK, diminished OT, but did not alter VP gene transcripts. Intracerebroventricular CP-472555 delivery in conjunction with antecedent NPH dosing prevented transcriptional habituation of GCK and OT genes, but did not modify CRH or VP mRNA profiles. The present data show that activation of PVN GR during antecedent intermediate insulin-induced hypoglycemia is required for exacerbation of recurring hypoglycemia, and receptor stimulation in the absence of hypoglycemia and/or its sequelae does not intensify the effects of subsequent NPH administration. The results also provide evidence for acclimation of PVN CRH, GCK, and OT gene profiles to serial NPH dosing, and demonstrate that GR may be involved in GCK and OT transcriptional adaptation to ongoing intermediate insulin-induced hypoglycemia.

Topics: Animals; Corticotropin-Releasing Hormone; Dexamethasone; Gene Expression Profiling; Gene Expression Regulation; Glucokinase; Hypoglycemia; Injections, Intraventricular; Insulin, Isophane; Male; Neuropeptides; Oxytocin; Paraventricular Hypothalamic Nucleus; Phenanthrenes; Pyridines; Rats; Receptors, Glucocorticoid; RNA, Messenger; Transcriptional Activation; Vasopressins

The insulin analogs, glargine and detemir, are associated with reduced hypoglycemia incidence compared with NPH insulin. We assessed the impact of changing basal insulin from NPH to glargine or detemir in patients with type 1 diabetes mellitus who experienced severe hypoglycemia.. A retrospective chart review was conducted that included 73 (31 female) patients (mean age 48 years, diabetes duration 19 years) treated for 12 to 24 months with insulin glargine (n = 43) or detemir (n = 30).. There were no patients who withdrew from treatment due to side effects. The mean treatment duration in both groups was 18 months. Changing from NPH insulin was associated with a -0.3% (p = 0.036) reduction in HbA1c for glargine (baseline 8.8%) and -0.4% (p = 0.040) for detemir (baseline 8.3%) treated patients; insulin dosages increased, respectively by 4.1 (p = 0.045) and 4.3 units (p = 0.004) (mean values). Weight did not increase significantly and the 1-year rate of serious hypoglycemia was 0.25/person/year.. Switching from NPH-insulin to insulin detemir or glargine in type 1 diabetes mellitus patients with previous serious hypoglycemia was associated with a reduction in HbA1c. However, severe hypoglycemia was not completely eliminated, and few patients reached internationally accepted glycemic treatment goals.. We searched Medline, PubMed (with key search terms type 1 diabetes, NPH insulin, detemir, glargine and serious hypoglycemia), reference lists and databases of ongoing and completed trials (through July 2008) provided from the manufacturers of the drugs to identify relevant literature.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Long-term studies involving large number of type 2 diabetic patients supplied evidence that constant adequate metabolic control may prevent the late (micro- and macrovascular) diabetic complications. In the present non-interventional, retrospective study, authors performed an analysis of type 2 diabetic patients who had been previously treated with biphasic human insulin (BHI) and their therapy was changed to biphasic analog insulin aspart 30/70 (BIAsp = NovoMix 30). The switch of the insulin therapy was carried out in years 2007 and 2008 with the cooperation of 50 accredited diabetes centers. Data were obtained at the time of therapeutical change and six months later. The number of suitable patients was 2898 with an age of 66.20 +/- 10.10 year, and the duration of diabetes was >10 years in 43% of the patients. After the six-month therapy with NovoMix 30, the mean HbA 1c level decreased statistically significantly from the initial value of 9.10 +/- 1.44% to 7.62 +/- 1.00% ( p < 0.001). The lipid profile also improved although target values were not always attained. A reduction was also observed in both systolic and diastolic blood pressure. Mean body weight decreased from 84.2 +/- 14.9 kg to 82.6 +/- 13.9 kg ( p < 0.01). All these changes occurred in spite of a significantly reduced daily insulin dose (48.4 +/- 17.6 IU) as compared with the initial value (49.0 +/- 17.4 IU, p < 0.001). A marked decrement was also observed in the frequency of hypoglycemic reactions. These results confirm that treatment with NovoMix 30 insulin leads to a significant amelioration of glycemic control as reflected by the decreased level of HbA 1c and the higher proportion of patients attaining the target value, as well as the lower frequency of hypoglycemic episodes. The significant improvements in cardiovascular risk factors are also important, but the explanation is still missing and would require the accomplishment of prospective, controlled studies.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hungary; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Risk Factors; Time Factors; Weight Gain

This article reevaluates the hypoglycemic episodes reported as severe in the Treat-to-Target Trial comparing insulin glargine and NPH insulin use in patients with inadequately controlled type 2 diabetes.. Case report forms from the Treat-to-Target Trial were reviewed to identify additional severe hypoglycemic events and to further characterize those events already identified. Severe hypoglycemia was defined as symptoms consistent with hypoglycemia requiring assistance of another person and associated with either glucose levels < or =56 mg/dL or prompt recovery after oral carbohydrate intake, intravenous glucose administration, or glucagon injection.. This analysis confirmed that severe hypoglycemia was similarly uncommon with both insulins (insulin glargine [n = 367], nine patients, 14 events; NPH insulin [n = 389], nine patients, 13 events); all hypoglycemic events for glargine and nine for NPH were treated effectively at home. All severe hypoglycemic episodes were associated with sulfonylurea use. A review of case report forms demonstrated inconsistencies in identification of severe hypoglycemia (seven of 14 severe events for glargine and three of 13 severe events for NPH were coded as moderate).. The rate of severe hypoglycemia in this trial was low. Difficulties in gathering and interpreting hypoglycemia data highlight the need for more objective methods.

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

The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs).. IMPROVE is a 26-week, open-label, non-randomised, international observational study in type 2 diabetes patients prescribed BIAsp 30 in routine clinical practice. The total cohort comprised 52 419 patients from various pre-study therapies. Here results from the subgroup of previously insulin-naïve patients are reported. Changes in glycated haemoglobin (HbA(1c)), fasting blood glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of patients achieving HbA(1c) < 7.0%, and rates of major and minor hypoglycaemic events were recorded. Treatment satisfaction was assessed using a validated questionnaire.. A total of 29 160 insulin-naïve patients were included; mean age 55.6 years, diabetes duration 7.3 years, baseline HbA(1c) 9.24%. Significant reductions were seen for HbA(1c) (-2.12%; p < 0.0001), FBG (-4.07 mmol/L; p < 0.0001) and PPBG after all meals (mean: -5.27 mmol/L; p < 0.0001); 39.2% of patients achieved HbA(1c) < 7.0% without hypoglycaemia. Better glycaemic control was seen in patients treated with BIAsp 30 twice-daily (BID) both at baseline and final visit, or BID at baseline and three-times daily at final visit, compared with other regimens. The rate of major hypoglycaemic events decreased significantly, while the rate of minor hypoglycaemic events increased. Better glycaemic control and a lower rate of minor hypoglycaemia were observed in patients using BIAsp 30 without OADs than with OADs. There was no clinically relevant change in weight (-0.07 kg; p < 0.0001). At final visit, 59.7% of patients were extremely/very satisfied with treatment, compared with 10.2% at baseline.. This open-label, non-randomised, observational study demonstrated that initiating insulin therapy with BIAsp 30 significantly improved glycaemic control in insulin-naïve patients previously poorly controlled on OADs. The rate of major hypoglycaemia was reduced and treatment satisfaction increased after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved with BIAsp 30 without OAD compared to with OAD.

Topics: Administration, Oral; Adult; Aged; Biphasic Insulins; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Retrospective Studies; Surveys and Questionnaires; Treatment Failure; Treatment Outcome

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

The PRESENT study was a 6-month multinational observational study in patients with type 2 diabetes receiving biphasic insulin aspart 30 (BIAsp 30). Data from PRESENT were analysed according to predefined subgroups stratified by age, body mass index (BMI) and ethnic origin. Achieved HbA1c levels were similar in each of: four age subgroups (<40 years 7.82%, 40-50 years 7.70%, 50-60 years 7.75%, >or=65 years 7.75%); five BMI subgroups (<25 kg/m(2): 7.78%, 25-30 kg/m(2): 7.58%, 30-35 kg/m(2): 7.57%, 35-40 kg/m(2): 7.74%, >or=40 kg/m(2): 7.93%); and Asian/Pacific Islander, Middle Eastern/Asian, White ethnic-origin subgroups (7.78%, 7.40%, 7.59%, respectively). The Black ethnic-origin subgroup had a higher baseline HbA1c of 11.61% (other groups 9.29-9.63%) and achieved a final HbA1c of 8.59%. Major hypoglycaemia was reported by fewer than 1% of subjects in any subgroup at end of study; overall end of study hypoglycaemia rates were less than four events/subject year (all subgroups). In conclusion, data from subgroups in the PRESENT study indicate that BIAsp 30 can be initiated and titrated effectively to help patients of all ages, of all degrees of obesity, and from a variety of ethnic origins, to achieve clinically relevant improvements in glycaemic control with low rates of hypoglycaemia.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Ethnicity; Female; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Multicenter Studies as Topic

The PREDICTIVE study is a multinational observational study designed to follow up patients with diabetes who started insulin detemir (IDet) in routine care. Recruitment started in June 2004 and is ongoing in some countries.. We report 12-week follow-up data for patients with type 1 (T1D) or type 2 diabetes (T2D) in the European cohort who, as part of basal-bolus therapy, switched from once- (qd) or twice-daily (bid) neutral protamine Hagedorn insulin (NPH) to qd IDet. End-points - evaluated from patients' records and diaries - were incidence of serious adverse drug reactions, glycaemic parameters, hypoglycaemia and weight change.. A total of 3637 patients were included, n = 1500 T1D [mean age 40.9 years, body mass index (BMI) 25.0 kg/m(2), glycosylated haemoglobin (HbA(1c)) 7.9%] and n = 2137 T2D (mean age 60.5 years, BMI 31.9 kg/m(2), HbA(1c) 8.0%). IDet was well tolerated. Lower overall, major and nocturnal rates of hypoglycaemia were observed in T1D and T2D patients switching from NPH to IDet (overall, T1D: 38.2-18.56 episodes/patient year, p < 0.001; T2D: 13.8-3.3 [corrected] episodes/patient year, p < 0.001). Switching from bid NPH to qd IDet resulted in significant 12-week reductions in HbA(1c) (T1D: -0.40%; T2D: -0.56%; both p < 0.001). Switching from qd NPH to qd IDet, resulted in HbA(1c) reductions of: T1D -0.52%; T2D -0.56%; both p < 0.001. Fasting blood glucose levels were also significantly reduced in patients with T1D or T2D. Overall mean weight changes were: T1D: 0.0 kg, T2D: -0.2 kg after 12 weeks.. In routine care, patients with T1D or T2D may be switched from NPH to IDet qd as part of a basal-bolus regimen.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study was done to assess the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice.. This was a prospective, multicentric, multinational, observational study in type 2 diabetes patients. The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs). We present the results of 6 months of treatment in the Indian cohort (n = 3559) with type 2 diabetes mellitus who were inadequately controlled on current treatment.. At three and six months, significant reductions from baseline were observed in the mean glycated haemoglobin (HbA1c) (-1.32% and -1.94%), fasting plasma glucose (-56.16 mg/dl and -75.24 mg/dl) and post-prandial plasma glucose (-88.74 mg/dl and -119.16 mg/dl) (p < 0.001). A significantly greater proportion of patients achieved target HbAlc of less than 7% at six months (31.1%), compared with baseline (3.1%), of which 70.4% did not report hypoglycaemia. The rate of total hypoglycaemia was reduced from 3.1 events per patient-year at baseline to 1.5 events per patient-year at end of the study. Episodes were mostly minor and diurnal. Except for two serious adverse drug reactions (ADRs) reported by one patient at 3 months, there were no reports of ADRs during the treatment period. More than 95% of patients and doctors were "very satisfied" or "satisfied" with BIAsp 30 treatment, compared to previous treatment.. The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in poorly controlled Indian type 2 diabetes patients. Both patients and doctors showed a high degree of treatment satisfaction.

Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin, Isophane; Prospective Studies; Racial Groups; Treatment Outcome

Hypoglycemia is a common consequence of achieving tight glycemic control for patients with type 2 diabetes, with clinical effects ranging from occasional mild discomfort to incapacitation, coma, or in rare cases, death. Severe hypoglycemic events, particularly those resulting in emergency medical intervention or hospitalization, incur substantial medical costs for patients and the healthcare system. Although vigilance is needed for the possibility of severe events, hypoglycemia need not be a barrier to effective glycemic control in type 2 diabetes. Data from clinical trials and meta-analyses have demonstrated that the basal insulin analog insulin glargine results in a reduced rate of severe hypoglycemic events compared with conventional insulin therapy such as neutral protamine Hagedorn (NPH) insulin. Overall, use of insulin glargine compared with NPH insulin appears to reduce the risk of nocturnal and severe hypoglycemia by 40% to 60% and may result in cost savings. Analyses of hypoglycemia rates from "real-world" clinical practice databases and retrospective analyses of medical claims data also have revealed reduced rates with insulin glargine, consistent with the findings from clinical trials.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insurance Claim Review; Medical Records Systems, Computerized; Meta-Analysis as Topic; Randomized Controlled Trials as Topic

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

To determine how young adults with insulin therapy manage daily care of diabetes during the physically demanding conditions of conscript military service, and to evaluate the effects of military service on glycaemic control and on the incidence of acute diabetic complications.. An observational study of 47 young male volunteer conscripts receiving insulin therapy was carried out at the Signal Regiment in Riihimäki from January 2001 to July 2005. Outcome measures were drop-out rate from service, management of diabetes care, glycaemic control, and occurrence of severe hypoglycaemia or ketoacidosis during service.. Forty (85%) diabetic conscripts completed service, with service time ranging from 180 to 362 days, and seven (15%) interrupted service. One-third of conscripts reported difficulties during military training with insulin injections and blood glucose testing. The mean HbA(1c) during service increased by 0.6% units (P = 0.007) from baseline. Five events of severe hypoglycaemia in three conscripts (overall incidence rate 0.15 per patient-year) and one ketoacidosis event occurred. Diabetic conscripts were chosen for leadership training more often than non-diabetic conscripts.. Our data suggest that selected and motivated adolescents on insulin therapy can manage the daily care of diabetes and maintain appropriate glycaemic control during service, although the risk of severe hypoglycaemia exists.

Topics: Adolescent; Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Male; Military Personnel; Risk Factors

The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation (PREDICTIVE) Study is a large, multi-centre, observational study assessing the safety and efficacy of insulin detemir in everyday clinical practice.. This subgroup analysis of the German cohort of PREDICTIVE evaluates over 3 months, patients with type 2 diabetes who were transferred to insulin detemir +/- oral antidiabetic drugs (OADs) from an OAD-only regimen (n = 1321), NPH insulin +/- OADs (n = 251) or insulin glargine +/- OADs (n = 260).. Among all groups, 3 months after starting treatment with insulin detemir, total, daytime and nocturnal hypoglycaemic events/patient were reduced by 84, 80 and 90%, respectively, from baseline. No major hypoglycaemic events were reported during treatment with insulin detemir. HbAlc was significantly reduced from baseline in each of the subgroups (-1.29,-0.60 and-0.59% for patients previously taking OADs only, NPH insulin +/- OADs and insulin glargine +/- OADs respectively; p < 0.0001), as was fasting blood glucose (FBG) (-58.1,-29.1 and-24.6 mg/dl; p < 0.0001) and FBG variability-8.2 mg/dl,-5.7 mg/dl; p < 0.0001 and -5.1 mg/dl; p = 0.0008). All subgroups combined lost an average of 0.9 kg of body weight (p < 0.0001) during the study. Total daily basal insulin dose increased slightly from baseline for those patients on a prior insulin regimen, and in this study 79% of patients used insulin detemir once daily.. These data confirm the short-term safety and efficacy of insulin detemir +/- OADs in a real-world scenario and support the findings of randomized controlled clinical trials with insulin detemir, including its limited effects on body weight.

Topics: Administration, Oral; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Loss

This observational study in patients with type 2 diabetes failing oral agent therapy with or without basal insulin was conducted to assess whether addition and self-titration of biphasic insulin aspart 70/30 (BIAsp 30) could achieve American Association of Clinical Endocrinologists (AACE)/International Diabetes Federation (IDF) and American Diabetes Association (ADA) glycemic targets (HbA(1c)< or =6.5 and <7%).. Enrolled patients (n = 100, HbA(1c)> or =7.5 and < or =10%) were > or =18 years of age, had diabetes > or =12 months and had received a stable antidiabetic regimen for at least 3 months [minimum of two oral antidiabetic drugs (OADs) or at least one OAD plus once-daily basal insulin < or =60 U]. Patients discontinued prior basal insulin and added one injection of BIAsp 30 (12 U or 70-100% of prior basal insulin dose within 15 min of dinner initiation). Patients self-titrated their BIAsp 30 dose with investigator guidance every 3 or 4 days to achieve pre-breakfast fasting blood glucose (FBG) of 80-110 mg/dl. At 16 weeks, a pre-breakfast injection of 6 U of BIAsp 30 was added if week 15 HbA(1c) exceeded 6.5%; the added dose was titrated to achieve pre-dinner BG of 80-110 mg/dl. After an additional 16 weeks, 3 U of pre-lunch BIAsp 30 was added if HbA(1c) exceeded 6.5%. This added dose was adjusted based on 2-h post-lunch BG to achieve postprandial glucose of 100-140 mg/dl. Subjects achieving an HbA(1c)< or =6.5% at 15 and 31 weeks completed the study at weeks 16 and 32 respectively.. Addition of once-daily BIAsp 30 before dinner enabled 21% of the patients to achieve AACE and IDF targets (HbA(1c)< or =6.5%) and 41% to achieve ADA targets (HbA(1c) <7%). With two daily injections of BIAsp 30, these glycaemic goals were achieved by 52 and 70% of subjects. With three daily BIAsp 30 injections, 60% of patients achieved HbA(1c)< or =6.5%, and 77% achieved HbA(1c) <7.0%.. This clinical trial demonstrates that initiation of once-daily BIAsp 30 to type 2 diabetes patients poorly controlled on various OAD regimens was an effective treatment approach for achieving glycaemic goals. Additional patients safely achieved these goals by increasing the number of BIAsp 30 injections from one to two, and then, if uncontrolled, from two to three doses per day. Eventually, most patients previously uncontrolled on OADs with or without basal insulin were controlled by the addition and vigorous titration of BIAsp 30 to oral agent therapy.

Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Cholesterol; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Treatment Outcome

Neurons that synthesize the potent orexigenic neuropeptide, orexin-A (ORX-A) are confined to the lateral hypothalamic area (LHA) and adjacent structures, and project throughout the central neuroaxis to structures that govern central nervous system responses to energy imbalance. Insulin-induced hypoglycemia (IIH) upregulates prepro-orexin mRNA and Fos immunostaining of LHA ORX-A neurons. These neurons apparently become desensitized to this metabolic challenge, since both responses are diminished by recurrent insulin-induced hypoglycemia (RIIH). Recent studies implicate central type II glucocorticoid receptors (GR) in RIIH-associated glucose counterregulatory collapse and decline in Fos labeling of central metabolic loci, including the LHA. The present studies evaluated the role of GR in patterns of LHA ORX-A neuronal transcriptional activation during RIIH. Groups of adult male rats were injected subcutaneously with one or four doses of the intermediate-acting insulin, Humulin NPH, on as many days, or with diluent alone. Rats injected with four doses of insulin were pretreated by intracerebroventricular (icv) administration of the selective GR antagonist, CP-472555, or the vehicle, propylene glycol, prior to insulin administration on days 1-3. All animals were sacrificed by transcardial perfusion 2h after injections on day 4. Processing of LHA tissue sections for dual-immunoperoxidase staining of ORX-A- and Fos-immunoreactivity (-ir) showed that colabeling of ORX-A neurons for Fos was increased by a single injection of NPH, whereas this genomic response was diminished by RIIH. Icv administration of CP-472555 during antecedent hypoglycemia prevented RIIH-associated reductions in Fos expression by these neurons. Antagonist treatment of diluent-injected controls did not alter mean numbers of ORX-A- plus Fos-ir neurons. Total numbers of ORX-A-immunopositive neurons were not different among treatment groups. These data demonstrate that precedent central GR blockade prevents adaptation of LHA ORX-A neuronal reactivity to RIIH. These results provide unique pharmacological evidence that hypoglycemic hypercorticosteronemia diminishes activation of this neurotransmitter phenotype in this critical metabolic structure to subsequent hypoglycemia via central GR-dependent mechanisms.

Topics: Animals; Behavior, Animal; Drug Interactions; Hypoglycemia; Hypoglycemic Agents; Hypothalamic Area, Lateral; Immunohistochemistry; Insulin; Insulin, Isophane; Intracellular Signaling Peptides and Proteins; Male; Neurons; Neuropeptides; Oncogene Proteins v-fos; Orexins; Phenanthrenes; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid; Time Factors

The purpose of this study was to compare the effect of insulin glargine (glargine) and NPH insulin (NPH) on long-term outcomes in type 2 diabetes patients using the Diabetes Mellitus Model (DMM).. The DMM predicts short- and long-term complications over ten years using data in studies published previously. The main effect on outcome is the influence of the treatment on the HbA1c level which is simulated over time. The simulation was based on a cohort size of 10,000 type 2 diabetes patients taking either glargine or NPH. The best scenario, baseline scenario and worst case scenario were simulated based on differences of 0.13%, 0.44% and 0.85%, respectively, in HbA1c values and corresponding to potentially attainable improvements with comparable or lower hypoglycemia rates in glargine-treated patients and NPH-treated patients. Assumptions for scenarios 1, 2 and 3 were based on a regression analysis of clinical trial data (pooled data clinical trials comparing glargine and NPH) in which the effect of glargine on the HbA1c/hypoglycemia incidence ratio was superior to that of NPH.. The relative risks (RR, glargine/NPH) obtained for scenarios 1, 2 and 3 were 0.97, 0.89 and 0.81, respectively, for long-term microvascular complications and 0.99, 0.95 and 0.91, respectively, for long-term macrovascular complications. RR reductions ranged from 1% in the less optimistic scenario to > 20% in the "best case" scenario. Sensitivity analyses showed that variations in the mean baseline HbA1c values and duration of the diabetes were without effect on these outcomes.. Although there is a need to corroborate the results of these simulations with real, long-term clinical data, they have demonstrated that, assuming comparable or lower rates of hypoglycemia, a better glycemic control (HbA1c reduction) can be expected with glargine when compared to NPH together with a reduction in long-term complications, mortality and associated costs.

Topics: Computer Simulation; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sensitivity and Specificity

In a prospective study on 11 patients with Type 1 diabetes we evaluated the glycaemic control and hypoglycaemic episodes on a combination therapy of pre-mixed and glargine insulin. Glycosylated hemoglobin (HbA1C), fasting (FPG) and Post Prandial blood glucose (PPG) levels were recorded at baseline and three monthly intervals for a period of 6 months. The mean HbA1C reduced from 9.5 to 7.3 %, incidence of hypoglycemias from 1.6 to 0.8, mean FPG from 146.5 to 90.4 and mean PPG from 258.4 to 184 over a six-month observation period. This regimen also helps to avoid injection of insulin before lunch so that child's school schedule is minimally disturbed and yet the incidence of hypoglycemia is not increased.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies

Glargine (Lantus) is a recently approved, long-acting insulin analog that is increasingly being used in children with diabetes. The aim of this retrospective chart review was to summarize our experience in starting glargine in children and adolescents with diabetes. SUBJECTS AND STUDY METHODS: We reviewed the medical records of 71 children with type 1 diabetes (29 boys and 42 girls) who initiated glargine therapy to improve glycemic control between 1 June 2001 and 30 June 2002. Data were collected for 6 months before and 6 months after adding glargine.. Subjects' mean age [+/-standard deviation (SD)] at diagnosis of diabetes was 7.5 +/- 4.1 yr. Mean age at initiation of glargine therapy was 11.5 +/- 4.9 yr. The total daily long-acting insulin dose decreased by about 20% after initiating glargine therapy. There were no significant differences in hemoglobin A1c (HbA1c) and blood glucose control prior to and after initiating glargine therapy (HbA1c at baseline 8.9 +/- 1.6% and HbA1c after 6 months of glargine therapy was 8.9 +/- 1.5%). Overall, blood glucose concentrations did not differ significantly throughout the study. Patients who switched to glargine because of nocturnal hypoglycemia had a 65% decrease in nocturnal blood glucose reading less than 50 mg/dL. There were three seizures in the first week after initiating glargine therapy.. This retrospective study suggests that glargine is at least as effective as other long-acting insulins but that care must be taken during the conversion process to avoid hypoglycemia.

Topics: Adolescent; Blood Glucose; Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Osmolar Concentration; Retrospective Studies; Seizures; Treatment Outcome

In the last few years short-acting insulin analogs have become increasingly popular. Their introduction has unmasked serious deficiencies in the capacity of isophane insulin to provide a stable basal insulinaemia. The long-acting insulin analogs, insulin glargine and insulin detemir, have been developed as alternatives to isophane insulin. Insulin glargine has a long duration of action and has demonstrated its usefulness in diabetes type 2, specifically a lower incidence of (nocturnal) hypoglycaemia compared to isophane insulin, in clinical practice. Insulin detemir has a very low variability in absorption and also seems to reduce the risk of nocturnal hypoglycaemia in diabetes type 1. More studies are, however, needed. Because of the higher costs of these novel insulins, the decision to switch a patient from isophane insulin to an insulin analog has to be made on an individual basis.

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

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

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane

Patients with diabetes mellitus type I usually are treated with a multiple injection regimen comprising rapid-acting insulin before meals and intermediate-acting insulin at bedtime. Recently, the rapid-acting insulin analogue insulin LISPRO was introduced on the Dutch market. This form of insulin is very rapidly taken up into the bloodstream from the subcutaneous tissue. The advantages of the use of insulin LISPRO are the comfort of injecting the insulin just before a meal, the more rapid correction of incidental hyperglycaemia and the slightly lower incidence of (nocturnal) hypoglycaemia in comparison with conventional rapid-acting insulin. There is no argument in favour of switching diabetics to insulin LISPRO if they are well-controlled with normal rapid-acting insulin and have few episodes of hypoglycaemia. In some persons the duration of action of insulin LISPRO may be too short, leading to preprandial hyperglycaemia. This can be avoided by using a second injection of intermediate-acting insulin, either before breakfast or before lunch.

Topics: Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane

Topics: Adrenergic beta-Antagonists; Aged; Angina Pectoris; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diet, Diabetic; Fatal Outcome; Female; Humans; Hypertension; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Propranolol

To determine the incidence of significant nocturnal hypoglycemia occurring at home in young children with insulin-dependent diabetes mellitus using conventional therapy.. Sixty-one children (aged 2.6 to 8.5 years) were studied on one night, at home, with blood collection occurring at dinner, bedtime/supper, 11 PM, 2 AM, and breakfast, with subsequent laboratory analysis.. The proportion of subjects with blood glucose levels less than 64, 55, 45, and 36 mg/dl (3.5, 3.0, 2.5, and 2.0 mmol/L) was 37.8%, 17%, 13%, and 8%, respectively. Nocturnal hypoglycemia was associated with younger age (< 5 years 57% vs 5 to 8.5 years 36%; p < 0.001) and lowered glycosylated hemoglobin levels (HbA1c) with a greater than 50% incidence of hypoglycemia seen in subjects with HbA1c levels of less than 8.5%. The average HbA1c concentration was lower in the hypoglycemic group than in the nonhypoglycemic group (7.8 vs 8.3%; p < 0.02). Nocturnal hypoglycemia occurred with increasing frequency throughout the night in subjects less than 5 years of age (dinner, supper, 11 PM, 2 AM, and breakfast incidences being 0%, 12.5%, 26%, 33%, and 30%, respectively) but not in those older than 5 years. Carbohydrate intake at supper did not prevent subsequent hypoglycemia. Blood glucose levels at 11 PM were poor predictors of subsequent hypoglycemia at 2 AM in either the group as a whole or in the children less than 5 years of age. Symptom recognition of nocturnal hypoglycemia was decreased in younger children (< 5 years (36%) > 5 years (58%)), in those with a lower HbA1c, and when hypoglycemia occurred at breakfast rather than at dinner (0% vs 50%).. The incidence of nocturnal hypoglycemia in young children with insulin-dependent diabetes mellitus receiving conventional therapy is unacceptably high and is increased with lowered age and HbA1c concentration; the condition is often asymptomatic. Early-morning hypoglycemia is poorly predicted by a blood glucose determination at 11 PM and is not prevented by carbohydrate intake at supper. In younger children, blood glucose profiles should include early-morning measurements.

Topics: Age Factors; Blood Glucose; Child; Child, Preschool; Circadian Rhythm; Diabetes Mellitus, Type 1; Dietary Carbohydrates; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin, Isophane; Male; Predictive Value of Tests

Topics: Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Feeding Behavior; Glycated Hemoglobin; Humans; Hyperinsulinism; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane

The aim of the study was to determine the appropriate dose of subcutaneous insulin to induce "beta-cell rest" without any hypoglycemic risk, as the first stop in the investigation of its potential effect in preventing or delaying clinical diabetes mellitus onset in high-risk subjects. Four subjects at high risk for type I diabetes mellitus (first-degree relatives, islet cell antibodies (ICA)-positive, and with diminished first-phase insulin secretion) were compared with four healthy individuals. After hospitalization, urinary C-peptide excretion (UCP) and 24-hour serum profiles for glucose were measured before and after administration of NPH insulin 0.1, 0.2, and 0.3 U x kg body weight per day subcutaneously in a single dose on 4 consecutive days. After insulin 0.1 U x kg body weight, a significant inhibition of endogenous insulin secretion was observed in high-risk subjects, but not in control subjects. There was no further inhibition when a higher insulin dose (0.2 and 0.3) was administered. A sustained beta-cell rest was obtained after 3, 6, and 12 months of treatment with 0.1 U x kg body weight per day as outpatient therapy in high-risk subjects. With this dose, no subject developed hypoglycemia (plasma glucose <50 mg/dL), whereas this adverse effect was detected after 0.2 and 0.3 U x kg body weight in both groups. In conclusion, our results indicate that administration of NPH insulin 0.1 U x kg bodyweight per day induces beta-cell rest without the undesirable effect of hypoglycemic episodes. This is a preliminary study to investigate the potential beneficial effect of insulin in preventing or delaying type I diabetes mellitus in subjects at high risk for the disease.

Topics: Adolescent; Adult; Case-Control Studies; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Secretion; Insulin, Isophane; Islets of Langerhans; Middle Aged; Prediabetic State; Risk Factors; Safety; Time Factors

A clinical transfer trial was conducted to ascertain whether semisynthetic human NPH insulin has a full 24-hour duration of therapeutic effect comparable to that of NPH insulin from animal sources. Diabetic patients requiring insulin and stabilized on a once-a-day (QD) regimen of animal NPH insulin were enrolled and entered a two-week run-in period during which the constancy of their insulin requirements and the stability of their glycemic control were assessed. At the end of the run-in phase, baseline measurements were made of fasting blood glucose (FBG), hemoglobin A1 C, C-peptide, and insulin antibodies. Patients then were transferred to a QD regimen of semisynthetic human NPH insulin (Novolin N) in the same dose as the animal insulin. Glycemic control was reassessed after 1, 4, and 8 weeks of therapy, and a global assessment of overall glycemic control was made at the conclusion of the study. Efficacy variables were analyzed for 39 patients. Most had non-insulin-dependent diabetes mellitus (NIDDM) and most were transferred from mixed beef/pork insulin. Six (15%) patients required significant adjustments in insulin dose or regimen; the remaining 85% completed the eight weeks of treatment with minimal changes in insulin dose. Mean values for FBG and hemoglobin A1 C did not change significantly between baseline and the end of the study. The only statistically significant change was an increase in mean body weight (P less than or equal to 0.01). Results of the investigators' global assessments showed that 74% of the patients had unchanged or improved control of glycemia after transferring to semisynthetic human NPH insulin. The average frequency of hypoglycemic events was not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus; Humans; Hypoglycemia; Immunoglobulin G; Insulin Antibodies; Insulin, Isophane; Time Factors

The course of a diabetic patient who self-administered 2500 U of NPH insulin subcutaneously was examined in detail. Despite resumption of oral intake on day 3, she required iv glucose for 6 days, during which time serum free insulin levels remained elevated. Glucose requirements closely matched those calculated from published euglycemic clamp data on maximal glucose disposal rates during insulin infusion. We postulate that her prolonged course was due to delayed absorption of the subcutaneous insulin. This is the first case of massive insulin overdose studied in such detail, and the results may facilitate management of future cases.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Overdose; Female; Glucose; Humans; Hypoglycemia; Injections, Intravenous; Insulin, Isophane; Suicide, Attempted

While fibrocalculous pancreatic diabetes (FCPD) has long been recognized in neighboring Indonesia, there has been only one single case reported from Papua New Guinea. Over an eighteen month period, four new cases of FCPD were seen at this hospital, making FCPD the predominant form of diabetes seen in Papua New Guinea highlanders. Abdominal pain was prominent in only one patient. Cassava formed a small part of the diet of all patients. Control with tolbutamide alone was possible in two patients and the addition of a small dose of isophane insulin gave satisfactory control in the other two. Two patients were particularly sensitive to low doses of insulin.

Topics: Adult; Calcinosis; Diabetes Mellitus; Female; Humans; Hypoglycemia; Insulin, Isophane; Male; Middle Aged; Nutrition Disorders; Pancreatic Diseases; Papua New Guinea; Patient Compliance; Radiography; Tolbutamide

Suicide attempts using hypoglycemic agents are uncommon but are associated with a high level of morbidity and mortality. Their recognition is sometimes difficult and the duration of hypoglycemic effect is often prolonged. Two cases that illustrate the difficulties encountered in recognition and therapy are described. Effective therapy depends on adequate glucose supplementation to maintain euglycemia. Therapeutic intervention often must be maintained for several days. Glucocorticoids may be useful in difficult cases. Other modes of therapy, including glucagon, are unproven or controversial.

Topics: Adolescent; Adult; Female; Glucagon; Glucose; Humans; Hypoglycemia; Insulin, Isophane; Suicide, Attempted; Sulfonylurea Compounds; Tolbutamide

Topics: Child; Diabetes Mellitus, Type 1; Enuresis; Glycosuria; Home Nursing; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Patient Compliance; Self Medication

Topics: Adult; Age Factors; Aged; Body Weight; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hospitalization; Humans; Hypoglycemia; Insulin; Insulin Resistance; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood Glucose; Boston; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Haptoglobins; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Male; Middle Aged; Regression Analysis

Topics: Adolescent; Attitude to Health; Child; Child Behavior Disorders; Child, Preschool; Diabetes Mellitus, Type 1; Diet, Diabetic; Female; Humans; Hypoglycemia; Infant; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male; Outpatient Clinics, Hospital; Parents

Topics: Acidosis; Animals; Blood Glucose; Fasting; Fatty Acids, Nonesterified; Female; Glucagon; Glycerol; Hypoglycemia; Insulin, Isophane; Ketones; Lipids; Phlorhizin; Sheep; Sheep Diseases

Topics: Blood Glucose; Diabetes Mellitus; Diet Therapy; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting

Topics: Animals; Appetite; Behavior, Animal; Blood Glucose; Body Weight; Central Nervous System Diseases; Chickens; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Liver; Organ Size; Ovulation; Pharmacology; Poultry; Protamines; Research

Topics: Diabetes Mellitus; Diabetic Angiopathies; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Protamines

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting

Topics: Adrenal Cortex; Blood Chemical Analysis; Blood Glucose; Corticosterone; Hyperinsulinism; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Long-Acting; Pharmacology; Pituitary-Adrenal Function Tests; Protamines; Rats; Research

Topics: Administration, Intravenous; Blood Glucose; Coma; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane

Topics: Biphasic Insulins; Globins; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Zinc