Open AccessPharmacokinetic and pharmacodynamic properties of insulin degludec in Japanese patients with type 1 diabetes mellitus reflect similarities with Caucasian patients
Author(s) -
Ikushima Ippei,
Kaku Kohei,
Hirao Koichi,
Bardtrum Lars,
Haahr Hanne
Publication year - 2016
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12399
Subject(s) - medicine , pharmacokinetics , crossover study , pharmacodynamics , area under the curve , dosing , diabetes mellitus , insulin degludec , insulin , type 2 diabetes , gastroenterology , pharmacology , urology , endocrinology , basal insulin , placebo , alternative medicine , pathology
The present study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec ( ID eg) 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 ID eg 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 [ AUC GIR ,τ, SS ]) was 1,446 mg/kg and total exposure (geometric mean) of ID eg ( AUC ID eg,τ, SS ) was 81,270 pmol h/L. Both the glucose‐lowering effect and the exposure of ID eg were evenly distributed over the dosing interval, with AUC for the first 12‐h intervals being approximately 50% of the total (geometric mean; AUC GIR ,0–12h, SS / AUC GIR ,τ, SS = 48%; AUC ID eg,0–12h, SS / AUC ID eg,τ, SS = 53%). Conclusions ID eg 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 ID eg in all patients. Overall, the pharmacodynamic and pharmacokinetic end‐points and safety observations are consistent with those previously reported in Caucasian patients.