Abstract
INTRODUCTION: The present study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg) in Japanese patients with type 1 diabetes. MATERIALS AND METHODS: This was a randomized, single-center, double-blind, two-period, crossover, multiple-dose trial. Patients were randomized into two treatment sequences, and received IDeg or insulin detemir for 6 days and a washout period (7-21 days) before switching treatment. Blood samples for pharmacokinetic measurements were obtained before each dose and up to 120 h after the last dose of each treatment period. Pharmacodynamic measurements were obtained using a 26-h euglycemic clamp procedure after the last dose of each treatment period. RESULTS: A total of 22 patients were randomized (14 men, 8 women; mean glycosylated hemoglobin at baseline of 7.5% [based on Japanese Diabetes Society value]). At steady state, total glucose-lowering effect (area under the glucose infusion rate [GIR] curve during one dosing interval [τ, 0-24 h] at steady state [AUCGIR ,τ, SS]) was 1,446 mg/kg and total exposure (geometric mean) of IDeg (AUCID eg,τ, SS) was 81,270 pmol h/L. Both the glucose-lowering effect and the exposure of IDeg were evenly distributed over the dosing interval, with AUC for the first 12-h intervals being approximately 50% of the total (geometric mean; AUCGIR ,0-12h, SS/AUCGIR ,τ, SS = 48%; AUCID eg,0-12h, SS/AUCID eg,τ, SS = 53%). CONCLUSIONS: IDeg has a flat, consistent and ultra-long glucose-lowering effect that is evenly distributed across a 24-h interval and an ultra-long duration of action in Japanese patients with type 1 diabetes. These data support once-daily dosing of IDeg in all patients. Overall, the pharmacodynamic and pharmacokinetic end-points and safety observations are consistent with those previously reported in Caucasian patients.