A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects. Methods In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg ( n = 8), 1.0 mg ( n = 8), placebo 0.5 mg ( n = 3) or 1.0 mg ( n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC 0–168h )]. Results Steady-state exposure of semaglutide was similar for both populations: AUC 0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration ( C max ) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC 0–168h ERR 1.11; C max ERR 1.14). Dose-dependent increases in AUC 0–168h and C max occurred in both populations. Accumulation was as expected, based on the half-life ( t 1/2 , ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified. Conclusions The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects. Funding Novo Nordisk A/S, Denmark. Trial registration ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.