1738-P: Efficacy and Hypoglycemia Outcomes with Once-Weekly IcoSema vs. Comparators in T2D by Baseline A1C: COMBINE 1–3

Introduction and Objective: This post hoc analysis assessed efficacy and hypoglycemia outcomes of IcoSema (a once-weekly combination of insulin icodec + semaglutide) vs comparators (COMBINE 1 [C1]: icodec; COMBINE 2 [C2]: semaglutide 1.0 mg; COMBINE 3 [C3]: basal-bolus therapy) in insulin-experienced (C1+3) or GLP-1 RA-experienced (C2) adults with T2D by baseline A1C subgroups. Methods: Treatment outcomes were analyzed across baseline A1C subgroups (<8.5% and ≥8.5%) by trial. Results: In C1, a greater treatment difference for change in A1C in favor of IcoSema was seen in the subgroup with baseline A1C ≥8.5% (p value for treatment by subgroup interaction 0.0018). In C2+3, treatment differences for change in A1C was comparable between baseline A1C subgroups (p value for treatment by subgroup interaction >0.05). Treatment differences for body weight change (baseline to wk 52) was consistent across A1C subgroups in C1-3, with no statistically significant treatment by subgroup interactions. For C1 + 3, rates of clinically significant or severe hypoglycemia were overall numerically lower with IcoSema vs comparators, irrespective of baseline A1C. The odds ratios for achievement of the composite endpoint were comparable between subgroups in C1-3 (p value for treatment by subgroup interaction >0.05, Figure). Conclusion: Efficacy and hypoglycemia outcomes for IcoSema vs comparators were generally consistent across A1C subgroups. Disclosure V. Mohan: None. R. Maltesen: Employee; Current; Novo Nordisk. L. Pletsch Borba: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. C. Scavenius: Employee; Current; Novo Nordisk. D. Yabe: Speaker's Bureau; Current; Abbott Japan Co., Ltd. Advisory Panel; Current; AstraZeneca, Amgen K.K., Eli Lilly KK, Dexcom, Inc., Kowa Company, Ltd., Sanofi. Speaker's Bureau; Current; Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Current; Boehringer Ingelheim International GmbH, Novo Nordisk. L. Ji: None.