Glucose-lowering effects and safety of DS-8500a, a G protein-coupled receptor 119 agonist, in Japanese patients with type 2 diabetes: results of a randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase II study.

OBJECTIVE

DS-8500a is a novel G protein-coupled receptor 119 agonist being developed for the treatment of type 2 diabetes. The study objective was to assess the efficacy and safety of DS-8500a in Japanese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

In this double-blind, parallel-group, phase II study, 99 Japanese patients with type 2 diabetes were randomized to receive placebo, or DS-8500a 10 mg or 75 mg once daily for 28 days. The primary efficacy endpoint was change in the 24-hour weighted mean glucose (WMG) from baseline (day -1) to day 28. Other endpoints included changes in fasting plasma glucose, postprandial glucose, lipids, and safety.

RESULTS

The 24-hour WMG decreased significantly after 28 days of treatment in the 10 mg and 75 mg groups with placebo-subtracted least squares mean differences (95% CI) of -0.74 (-1.29 to -0.19) mmol/L and -1.05 (-1.59 to -0.50) mmol/L, respectively. Reductions in 24-hour WMG in both DS-8500a groups were observed on day 14 and were greater on day 28 than on day 14. The reductions in fasting plasma glucose and 2-hour postprandial glucose were significantly greater in the 75 mg DS-8500a group versus placebo. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides decreased significantly; high-density lipoprotein cholesterol increased significantly in the 75 mg group versus placebo. Both doses of DS-8500a were well tolerated without significant treatment-related adverse events, hypoglycemia, or discontinuations due to adverse events.

CONCLUSIONS

DS-8500a significantly improved glycemic control and lipids and was well tolerated over 28 days of administration in Japanese patients with type 2 diabetes.

TRIAL REGISTRATION NUMBER

NCT02222350; Post-results.