Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes

Aims: Insulin degludec (IDeg) is a new-generation, ultra-long-acting basal insulin that forms soluble multihexamers upon subcutaneous injection, resulting in a depot from which IDeg is absorbed slowly and continuously into circulation. This double-blind, two-period, incomplete block cross-over trial investigated the pharmacodynamic and pharmacokinetic properties of IDeg at steady state (SS) in people with type 2 diabetes. Methods: Forty-nine subjects treated with insulin without concomitant oral anti-diabetic drugs were given IDeg (0.4, 0.6 and/or 0.8 U/kg) once daily for two 6-day periods, separated by an interval of 13-21 days. Following dosing on Day 6, subjects underwent a 26-h euglycaemic glucose clamp (Biostator (R); clamp blood glucose level: 90 mg/dl; 5.0 mmol/l). Pharmacokinetic samples were taken until 120 h after last dosing. Results: For all dose levels, the mean glucose infusion rate (GIR) profiles were flat and stable. The glucose-lowering effect of IDeg was evenly distributed over the dosing interval tau, with area under the curve (AUC) for each of the four 6-h intervals being approximately 25% of the total AUC (AUC(GIR,tau,SS)). Total glucose-lowering effect increased linearly with increasing dose. The blood glucose levels of all subjects stayed very close to the clamp target until end of clamp. The terminal half-life of IDeg was approximately 25 h at steady state. IDeg was well tolerated and no safety concerns were identified. No injection site reactions were reported. Conclusions: IDeg has a flat and consistent glucose-lowering effect in people with type 2 diabetes.