1816-P: Clinical Characteristics Associated with Secondary Failure of Imeglimin: Insights from Randomized Controlled Trials

Introduction and Objective: To assess the incidence of secondary failure (SF) in patients receiving imeglimin either as monotherapy or as add-on to insulin, and to characterize factors associated with SF. Methods: Data were derived from randomized, placebo-controlled, double-blind trials of imeglimin in Japanese patients with type 2 diabetes. The duration of trial was 24 weeks for the monotherapy and 16 weeks for the add-on to insulin therapy. For the imeglimin 1,000 mg bid arm, the time point of maximal HbA1c reduction and its value were identified for each patient. SF was defined as an HbA1c increase >0.3% from this nadir. Results: Among patients on imeglimin monotherapy, 25.7% met SF criteria. Compared with non-SF patients, SF patients were younger (57.2 vs 62.6 years) and more frequently had CKD stage 3a (26.1% vs 12.0%). HbA1c reduction began to wane at week 16 in SF, with significant differences from non-SF at weeks 20 and 24. Multivariable logistic regression showed age and eGFR were independently associated with SF (OR=0.93, 95% CI: 0.893-0.967, p<0.001; OR=0.969, 95% CI: 0.941-0.998, p=0.037). For imeglimin add-on to insulin, 18.5% met SF criteria. SF patients were younger (55.9 vs 60.0 years), less likely to have CKD stage 1 (5.0% vs 17.0%), and less likely to use basal insulin (55.0% vs 70.5%). In non-SF, imeglimin consistently improved HbA1c versus placebo at all time points. In SF, no significant difference from placebo was observed beyond week 12, with significant differences versus non-SF at weeks 12 and 16. Conclusion: A subset of patients with type 2 diabetes exhibits attenuated response to imeglimin over time. Early identification of SF may optimize therapeutic strategies. Further evaluation of imeglimin efficacy trajectories using real-world data is warranted. Disclosure K. Hagi: Employee; Current; Sumitomo Dainippon Pharma Co., Ltd. K. Kaku: Speaker's Bureau; Ended; Astellas Pharma Inc. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. Speaker's Bureau; Ended; Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation. Consultant; Current; Sanwa Kagaku Kenkyusho. Speaker's Bureau; Ended; Novo Nordisk, Taiho Pharmaceutical Co. Ltd. Speaker's Bureau; Current; Sumitomo Dainippon Pharma Co., Ltd. H. Watada: Research Support; Current; Sumitomo Pharma Co. Ltd., Sanwa Kagaku Kenkyusho, Kowa Company, Ltd., Taiho Pharmaceutical Co. Ltd., SBI pharma, Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Novo Nordisk, Boehringer Ingelheim International GmbH, Sumitomo Pharma Co. Ltd., Lilly, Roche Diagnostics, Merck Sharp & Dohme Corp., Daiichi Sankyo, Kyowa Kirin Co., Ltd., Bayer AG, Abbott Japan Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Teijin Pharma Limited, GlaxoSmithKline plc., Sanofi K.K., embecta. K. Ueki: Speaker's Bureau; Current; Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim International GmbH, AstraZeneca. Advisory Panel; Current; Abbott Japan Co., Ltd. Speaker's Bureau; Current; Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd.