Efficacy And Safety Of Imeglimin In Japanese Patients With Type 2 Diabetes Mellitus: A 24‐Week, Randomized, Double‐Blind, Placebo‐Controlled, Dose‐Ranging Phase 2b Trial

AIMS The aim of this study was to assess the efficacy and safety of imeglimin monotherapy compared to placebo for 24 weeks in Japanese patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS In this 24-week, randomized, double-blind, placebo-controlled, parallel group, dose ranging, phase 2b clinical trial, Japanese adults (age ≥ 20 years) with T2DM either treatment-naive or previously treated with one oral anti-diabetes agent were eligible for participation. Patients were randomly assigned (1:1:1:1) to receive orally imeglimin 500 mg or imeglimin 1000 mg or imeglimin 1500 mg, or placebo twice daily over a 24-week period. The primary endpoint was the placebo-adjusted change at week 24 in HbA1c. Safety outcomes were assessed in all patients that received at least one dose of study drug. This trial is registered at JAPIC (JapicCTI-153086). RESULTS A total of 299 patients were randomized to receive double-blind treatment with orally twice-daily placebo (n= 75), imeglimin 500 mg (n=75), 1000 mg (n=74) or 1500 mg (n=75). At week 24, imeglimin significantly decreased HbA1c (difference vs placebo: imeglimin 500 mg -0.52% (95% CI: -0.77, -0.27), imeglimin 1000 mg -0.94% (95% CI: -1.19, -0.68), imeglimin 1500 mg -1.00% (95% CI: -1.26, -0.75) (p < 0.0001 for all). Treatment-emergent adverse events (TEAE) were reported for 68.0%, 62.2%, 73.3% and 68.0% of patients receiving imeglimin 500 mg, imeglimin 1000 mg, imeglimin 1500 mg and placebo, respectively. A small increase in gastrointestinal adverse effects (e.g. diarrhea) occurred with the 1500 mg dose level. Hypoglycemia was balanced between groups. CONCLUSIONS Imeglimin as monotherapy in Japanese patients with T2DM was well tolerated and significantly improved glycemic control with no significant increase in hypoglycemic events versus placebo. Given the marginal increase in efficacy with the 1500 mg vs. 1000 mg dose (along with the potential for gastrointestinal tolerability issues), a dose of 1000 mg BID was selected for subsequent Phase III studies. This article is protected by copyright. All rights reserved.