1758-P: Efficacy and Hypoglycemia Outcomes with Once-Weekly IcoSema vs. Comparators in T2D by Baseline BMI: 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 BMI subgroups. Methods: Treatment outcomes were analyzed across baseline BMI subgroups (<25, ≥25-<30, ≥30-<35, ≥35 kg/m2) by trial. Results: Overall, treatment differences for change in A1C (baseline to wk 52) across BMI subgroups were consistent with the individual trial results, with no statistically significant treatment by BMI subgroup interactions (p>0.05). In C1+3, treatment differences for body weight change differed across BMI subgroups, with greater estimated treatment differences in higher BMI subgroups (p<0.05); there was no statistically significant treatment by subgroup interaction in C2. Rates of clinically significant or severe hypoglycemia were lower with IcoSema vs comparators in C1+3, irrespective of baseline BMI. In C1+3, the odds ratios for achieving the composite endpoint were consistent across BMI subgroups (p>0.05); in C2, there was a statistically significant treatment by subgroup interaction (p=0.0081, Figure). Conclusion: Efficacy and hypoglycemia outcomes for IcoSema vs comparators were generally consistent across BMI subgroups. Disclosure 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. R. Maltesen: Employee; Current; Novo Nordisk. V. Mohan: None. L. Pletsch Borba: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. C. Scavenius: Employee; Current; Novo Nordisk. L. Ji: None.