Dose-response relationship of insulin glulisine in subjects with type 1 diabetes

Aim: Little is known about the dose–response relationships of rapid-acting insulin analogues in subjects with diabetes. This study compared the dose–exposure and dose–response relationships of insulin glulisine and regular human insulin (RHI) in subjects with type 1 diabetes. Methods: Eighteen male subjects with type 1 diabetes (mean glycosylated haemoglobin, HbA1c, 7.7%; body mass index 24.5 kg/m2) received subcutaneous injections of insulin glulisine followed by RHI (both at doses of 0.075, 0.15 and 0.3 U/kg) in the same three-way crossover, randomized order in a euglycaemic glucose-clamp study. Results: Insulin glulisine and RHI showed dose-proportional increases in exposure (INS-AUCtotal) and maximum serum concentration (INS-Cmax) in the dose ranges 0.075, 0.15 and 0.3 U/kg. At all doses, within 2 h after injection, about twice as much insulin glulisine was absorbed as RHI (INS-AUC0–2h: 3855, 6832 and 13237 vs. 2356, 3630 and 6231 μU.min/mL; p