Efficacy and safety of the G protein‐coupled receptor 119 agonist DS‐8500a in Japanese type 2 diabetes mellitus patients with inadequate glycemic control on sitagliptin: A phase 2 randomized placebo‐controlled study

INTRODUCTION: We evaluated the efficacy and safety of DS‐8500a as add‐on therapy to sitagliptin in Japanese type 2 diabetes mellitus patients. MATERIALS AND METHODS: This multicenter, randomized, double‐blind, placebo‐controlled, phase 2 trial randomized patients aged ≥20 years with hemoglobin A1c ≥7.0% and <9.0%, and inadequate glycemic control with sitagliptin 50‐mg monotherapy to receive 25 or 75 mg DS‐8500a, or a placebo, orally. The primary end‐point was change from baseline to day 28 in 24‐h weighted mean glucose. Secondary end‐points included change from baseline in fasting plasma glucose, 2‐h postprandial plasma glucose and lipid profiles. RESULTS: Overall, 29, 28 and 27 patients in the placebo, 25‐ and 75‐mg groups, respectively, were analyzed. A significant dose‐dependent reduction was observed in 24‐h weighted mean glucose (linear: P = 0.0006, saturated at 25 mg: P = 0.0003, responded from 75 mg: P = 0.0176) when compared with the placebo (25 mg: −13.19 mg/dL [−0.73 mmol/L], P = 0.0044 vs placebo and 75 mg: −16.12 mg/dL [−0.89 mmol/L], P = 0.0006 vs placebo). A significant reduction in fasting plasma glucose at 75 mg vs placebo was observed (P < 0.001). At 25 and 75 mg, significant reductions of 2‐h postprandial plasma glucose (after breakfast), total cholesterol, low‐cholesterol and triglycerides were observed (all P < 0.05), with a (non‐significant) trend towards increased high‐density lipoprotein cholesterol. Both doses of DS‐8500a were well tolerated. There were no significant treatment‐emergent adverse events leading to discontinuation during the study. CONCLUSIONS: DS‐8500a was well tolerated, and showed significant glycemic benefits and favorable changes in lipid profile in Japanese type 2 diabetes mellitus patients with inadequate glycemic control with sitagliptin therapy.