1999-LB: The Efficacy of Imeglimin and Metformin on Insulin Sensitivity and Secretion Using Oral Minimal Model—Subanalysis of a Randomized Controlled Trial

Introduction and Objective: Imeglimin shares structural similarities with metformin, prompting investigation into the similarities and differences between the two drugs. We have previously demonstrated the difference in the effects on insulin and incretin secretion; however, the effect on insulin sensitivity during glucose loading requires further exploration. Methods: Patients with type 2 diabetes were randomized to imeglimin group (IME) or metformin group (MET), and OGTT was performed before and after 12 and 24weeks. Insulin sensitivity was assessed by sensitivity index (SI) calculated using the oral glucose minimal model. For beta-cell function, Φb, Φd, Φs, and Φ were calculated using the oral C-peptide minimal model. Results: SI was significantly increased in both IME and MET at 24 weeks and 12 weeks, respectively. In IME, Φs and Φ were significantly increased, while only limited changes were observed in MET. Furthermore, in IME, no correlation was found between change in Φ and baseline parameters. On the other hand, in MET, change in Φ at 24 weeks was negatively corelated with baseline Φ (ρ=-0.54, p=0.01). Conclusion: Imeglimin enhanced both insulin secretion and sensitivity regardless of patients’ background, while metformin primarily improved insulin sensitivity and exerted heterogeneous effects on beta-cell function, highlighting the distinct mechanisms of action between the two drugs. Disclosure R. Usui: Speaker's Bureau; Sumitomo Dainippon Pharma Co., Ltd, Abbott, Novo Nordisk. Y. Hamamoto: Research Support; Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd, Merck Sharp & Dohme Corp. Funding Research grant from Sumitomo Pharma Co.