2834-LB: Cardiometabolic Outcomes in Adults with T2D Treated with 1 mg Semaglutide Who Titrate to 2 mg Semaglutide vs. Switch to Tirzepatide

Introduction and Objective: Once-weekly (OW) injectable 2 mg semaglutide (SEMA 2mg) and OW tirzepatide (TZP) are superior to OW 1 mg semaglutide (SEMA 1mg) in reducing HbA1c and body weight in adults with T2D. This study assessed whether titration to SEMA 2mg was noninferior and/or superior to a switch to TZP for HbA1c and weight reductions in SEMA 1mg-treated adults. Methods: This retrospective cohort study identified adults with T2D treated with SEMA 1mg who titrated to SEMA 2mg or switched to TZP in Komodo’s Healthcare Map (1/1/18-9/30/25). Baseline characteristics were balanced with IPTW. A Cox proportional hazard model assessed an intention-to-treat analysis with noninferiority and superiority assessments for the primary outcomes—HbA1c <7% and ≥5% body weight loss. Results: HbA1c (n=64,888) and body weight cohorts (n=56,852) had a mean age (SD) of 58 (12) and 59 (12) yrs, were 52% and 60% White, respectively, and had balanced baseline characteristics between treatments. Titration to SEMA 2mg was noninferior (margin: 0.93), but not superior (margin: 1.07), in achieving HbA1c <7% (hazard ratio [HR]: 0.98; 95% CI: 0.94-1.02). Titration to SEMA 2mg showed noninferiority (margin: 0.92) and superiority (margin: 1.09) in the ≥5% body weight loss cohort vs a switch (HR: 1.19; 95% CI: 1.15-1.24). Conclusion: Titration to SEMA 2mg was noninferior in HbA1c goal attainment and superior in body weight reduction vs a switch to TZP in adults with T2D. Disclosure G. Fang: Employee; Current; Novo Nordisk. Employee; Ended; JAZZ Pharmaceuticals Inc. C. Muhammad: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. C. Swift: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. J. Noone: Employee; Current; Novo Nordisk. Y. Liang: Employee; Current; Novo Nordisk. K.S. Tierney: Speaker's Bureau; Current; Novo Nordisk, Dexcom, Inc.