insulin-glulisine and Obesity

A multinational, randomized, double-blind, two-way crossover trial to compare the pharmacokinetic and pharmacodynamic properties of bolus, subcutaneously administered insulin glulisine (glulisine) and insulin aspart (aspart) in insulin-naÏve, obese subjects with type 2 diabetes.. Thirty subjects [9/21 females/males; mean ± SD age: 60.7 ± 7.7 years; body mass index (BMI): 33.5 ± 3.3 kg/m(2) ; duration of diabetes: 6.8 ± 4.6 years; HbA1c: 7.1 ± 0.8%] were included in the analysis. They fasted overnight and then received a 0.2 U/kg subcutaneous dose of glulisine or aspart 2 min before starting a standardized test meal, 7 days apart, according to a randomization schedule. Blood samples were taken every 15 min, starting 20 min before the meal and ending 6 h postprandially.. The area under the absolute glucose concentration-time curve between 0 and 1 h after insulin injection and maximal glucose concentration was significantly lower with glulisine than with aspart (p = 0.0455 and 0.0337, respectively). However, for the total study period, plasma glucose concentration was similar for glulisine and aspart. Peak insulin concentration was significantly higher for glulisine than for insulin aspart (p < 0.0001). Hypoglycaemic events (≤ 70 mg/dl with or without symptoms) occurred in 13 and 16 subjects treated with glulisine and aspart, respectively, but there were no cases of severe hypoglycaemia requiring intervention.. Glulisine was associated with lower glucose levels during the first hour after a standard meal; the remaining glucose profiles were otherwise equivalent, with higher insulin levels observed throughout the study period.

Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Eating; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Male; Middle Aged; Obesity; Treatment Outcome

A comparison of the plasma glucose and insulin day profiles between two prandial rapid-acting insulin analogues, insulin glulisine (glulisine) and insulin lispro (lispro), in 18 obese subjects with Type 2 diabetes. Subjects (body mass index: males, 36.7 [33.2-43.8] kg/m(2); females, 40.0 [35.7-46.5] kg/m(2)) received subcutaneous glulisine or lispro (0.15 U/kg) at 4-h intervals immediately (within 2 min) before three standard test meals during each of two 12-h, randomised, open-label, crossover studies (7+/-2-day interval between each). Overall, preprandial-subtracted glucose concentrations (area under the curve) were similar on the glulisine and lispro study days. However, the mean of the three maximal preprandial subtracted plasma glucose concentrations (DeltaGLU(max)) were lower with glulisine versus lispro (12%; p<0.01). Mean concentrations of insulin analogue were significantly higher post-meal with glulisine (p<0.01 for all). Post hoc analysis showed a significantly faster absorption rate for glulisine versus lispro in the first 30 min post-meal (estimated difference 0.48 microU/min; p<0.0001). Only two cases of hypoglycaemia were reported; both from one subject during the lispro day. When glulisine is injected immediately before a meal in obese patients with Type 2 diabetes, glulisine achieves significantly lower glucose excursions over lispro. Significantly faster absorption with higher and sustained post-meal levels of insulin analogue was achieved at every meal with glulisine versus lispro.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Male; Middle Aged; Obesity

This study compared the pharmacokinetics and pharmacodynamics of insulin glulisine, insulin lispro, and regular human insulin in obese subjects.. In this single-dose, randomized, double-blind, crossover euglycaemic clamp study, 18 non-diabetic subjects (mean body mass index [BMI] 34.7 kg . m (-2)) were randomized to receive subcutaneous injections of each insulin (0.3 U . kg (-1)) in pre-determined sequences.. Insulin glulisine and insulin lispro had more rapid-acting profiles than regular human insulin. Fractional glucose infusion rate (GIR)-area under curves (AUC) of the GIR curve and maximum GIR were greater for insulin glulisine and insulin lispro versus regular human insulin. Total glucose disposal was slightly greater with insulin glulisine than with regular human insulin, and was comparable to insulin lispro, although it decreased with increasing insulin resistance (HOMA index) with all insulins. Time to 20 % (early glucose disposal) and 80 % (bulk of activity) of total GIR-AUC were shorter for insulin glulisine and insulin lispro versus regular human insulin. This was corroborated by more rapid and shorter residing pharmacokinetic profiles of insulin glulisine and insulin lispro versus regular human insulin, evidenced by shorter times to 20 % of total INS-AUC, INS-C (max) (INS-t (max)), and mean residence time. Moreover, time to 20 % of total GIR-AUC demonstrated a less rapid-acting profile for insulin lispro versus insulin glulisine, which was consistent with the slightly less rapid pharmacokinetic profile of insulin lispro. There was no significant correlation between BMI or subcutaneous fat thickness and pharmacokinetic or pharmacodynamic profiles for insulin glulisine, unlike insulin lispro and regular human insulin.. Insulin glulisine and insulin lispro demonstrated substantially more rapid time-action profiles than regular human insulin in obese non-diabetic subjects, which prevailed with insulin glulisine irrespective of BMI and subcutaneous fat thickness.

Topics: Adult; Blood Glucose; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Male; Middle Aged; Obesity; Time

Several studies suggest benefits of insulin analogues detemir or glulisine in overweight and obese patients with type 2 diabetes. The present multicentre study therefore examines, whether these insulin analogues are used more frequently in patients with increased body mass index.. Data of 38 560 adult type 2 diabetic patients using insulin analogues, from 150 centres in Germany, registered in a standardized, prospective, computer-based documentation program (DPV), were included. Patients were classified into body mass index categories according to World Health Organization. Analysis was stratified by 3 time periods. To adjust for confounding effects, multivariable logistic regression models were created.. Detemir was preferentially used in overweight (OR 1.36, 95%-CI 1.20-1.53) and obese patients (OR 2.06, 95%-CI 1.84-2.31) compared to normal-weight patients. These effects remained significant after adjusting for sex, age, new/old federal state of Germany, size of centre, treatment in university clinic and clinic/specialized private practice. Models were additionally adjusted for time period and interaction of BMI category with age or sex. For glulisine, a minor effect was present when comparing obese to normal-weight patients (OR 1.26, 95%-CI 1.06-1.50). After adjustment, this finding was no longer significant. Stratified by obesity grade, class III obese patients more frequently used detemir or glulisine compared to class I obese patients. Comparing time periods, odds ratios did not differ, neither for detemir nor for glulisine..  Detemir is used more often in overweight and obese patients compared to normal-weight patients. For glulisine, the relationship is less pronounced.

Topics: Aged; Body Weight; Databases, Factual; Diabetes Mellitus, Type 2; Drug Prescriptions; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Obesity; Overweight; Practice Patterns, Physicians'; Registries

Topics: Biological Availability; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Approval; Humans; Insulin; Obesity; Postprandial Period; Treatment Outcome