Evaluation of Efficacy, Safety, and Tolerability of Imeglimin Hydrochloride SR Tablets 1000 mg in Participants with Inadequately Controlled Type 2 Diabetes Mellitus: A Phase III, Randomized, Double-Blind, Active-Controlled, Parallel Group, Multicente

Abstract Background: Management of type 2 diabetes mellitus (T2DM) focuses on achieving target HbA1c levels, but poor glycemic control remains prevalent among Indian patients. The approval of imeglimin and its use in India highlight its potential as an effective treatment option, but the lack of phase III clinical trial data emphasizes the need for evidence-based research in this population. Aim: We aimed to evaluate the efficacy, safety, and tolerability of imeglimin hydrochloride sustained release (SR) tablets in participants with T2DM inadequately controlled with diet and exercise. Materials and Methods: This phase III, prospective, randomized, double-blind, active-controlled, multicenter clinical study was conducted (between January 2023 and July 2023) in India for 16 weeks. Treatment-naïve participants (18–65 years) with T2DM and inadequately controlled with diet and exercise for 3 months prior to screening were randomized (1:1) to either imeglimin or metformin SR 1000 mg once daily. Efficacy outcomes were mean change in HbA1c, FPG, and 2-h PPG from baseline to week 16. Adverse events were recorded. Results: Of the 216 randomized participants, 210 [imeglimin ( n = 106); metformin ( n = 104)] completed the study. Reductions in HbA1c (%) (−0.70 vs −0.67; P = 0.6994), FPG (mg/dL) (−17.88 vs −16.32; P = 0.5471), and 2-h PPG (mg/dL) (−26.96 vs −24.32; P = 0.5763) were comparable in both intervention arms. The proportion of participants (i) achieving therapeutic glycemic response was relatively higher (38.89% vs 37.03%; P = 0.7792), and (ii) those requiring rescue medications (6.48% vs 7.41%; P = 0.7890) were relatively less, in imeglimin treatment. Safety and tolerability parameters were comparable in both arms. Conclusion: Imeglimin demonstrated comparable efficacy to that of metformin with a similar safety profile.