AIM: This randomized, single-centre, double-blind, crossover study compared the pharmacodynamic and pharmacokinetic properties of two different doses of insulin glulisine (glulisine) and insulin lispro (lispro) in lean to obese subjects. METHODS:Eighty subjects without diabetes, stratified into four body mass index (BMI) classes (<25, >or=25 to <30, >or=30 to <35 and >or=35 kg/m(2)), were randomized to receive single injections of glulisine and lispro (0.2 and 0.4 U/kg) on four study days under glucose clamp conditions. Glucose infusion rates (GIR) and insulin (INS) concentrations were assessed for 10 h postdose. RESULTS:Glulisine showed a greater early metabolic action than lispro [GIR-area under the curve (GIR-AUC) between 0 and 1 h (0.2 U/kg: 102.3 +/- 75.1 vs. 83.1 +/- 72.8 mg/kg, p < 0.05; 0.4 U/kg: 158.0 +/- 100.0 vs. 112.3 +/- 70.8 mg/kg, p < 0.001)], with an earlier time to 10% of total GIR-AUC (0.2 U/kg: 1.4 +/- 0.4 vs. 1.5 +/- 0.4 h; 0.4 U/kg: 1.4 +/- 0.3 vs. 1.5 +/- 0.3 h, p < 0.05). The total metabolic effect was not different between the two insulins. In accordance with these findings, the time to 10% of total INS-AUC was faster with glulisine compared with lispro at either dose (0.2 U/kg: 0.7 +/- 0.2 vs. 0.8 +/- 0.2 h; 0.4 U/kg: 0.8 +/- 0.2 vs. 0.9 +/- 0.2 h, p < 0.001). The faster rise in insulin concentrations and the earlier onset of activity of glulisine vs. lispro was consistently observed in each individual BMI class. CONCLUSIONS:Glulisine shows a faster onset of action than lispro, independent of BMI and dose.
RCT Entities:
AIM: This randomized, single-centre, double-blind, crossover study compared the pharmacodynamic and pharmacokinetic properties of two different doses of insulinglulisine (glulisine) and insulinlispro (lispro) in lean to obese subjects. METHODS: Eighty subjects without diabetes, stratified into four body mass index (BMI) classes (<25, >or=25 to <30, >or=30 to <35 and >or=35 kg/m(2)), were randomized to receive single injections of glulisine and lispro (0.2 and 0.4 U/kg) on four study days under glucose clamp conditions. Glucose infusion rates (GIR) and insulin (INS) concentrations were assessed for 10 h postdose. RESULTS:Glulisine showed a greater early metabolic action than lispro [GIR-area under the curve (GIR-AUC) between 0 and 1 h (0.2 U/kg: 102.3 +/- 75.1 vs. 83.1 +/- 72.8 mg/kg, p < 0.05; 0.4 U/kg: 158.0 +/- 100.0 vs. 112.3 +/- 70.8 mg/kg, p < 0.001)], with an earlier time to 10% of total GIR-AUC (0.2 U/kg: 1.4 +/- 0.4 vs. 1.5 +/- 0.4 h; 0.4 U/kg: 1.4 +/- 0.3 vs. 1.5 +/- 0.3 h, p < 0.05). The total metabolic effect was not different between the two insulins. In accordance with these findings, the time to 10% of total INS-AUC was faster with glulisine compared with lispro at either dose (0.2 U/kg: 0.7 +/- 0.2 vs. 0.8 +/- 0.2 h; 0.4 U/kg: 0.8 +/- 0.2 vs. 0.9 +/- 0.2 h, p < 0.001). The faster rise in insulin concentrations and the earlier onset of activity of glulisine vs. lispro was consistently observed in each individual BMI class. CONCLUSIONS:Glulisine shows a faster onset of action than lispro, independent of BMI and dose.