SAT-696 A Comparison of Tirzepatide vs Semaglutide for Weight Reduction over 6 Months of Treatment in Adults with Obesity in US Clinical Practice Settings

Abstract Disclosure: C. Le Roux: Novo Nordisk, Roche Pharmaceuticals, Eli Lilly & Company, Johnson &Johnson, Boehringer Ingelheim, AstraZeneca, Amgen Inc, Abbvie, Herbalife, GI Dynamics, Gila, Irish Life Health, Currax, Zealand Pharma, Keyron, Arrowhead Pharma, Metsera, Nymble, Rhythm Pharma, EU Innovative Medicine Initiative, Irish Research Council, Science Foundation Ireland, Anabio, Health Research Board, Irish Society for Nutrition and Metabolism, My Best Weight clinic, Beyond BMI clinic. N. Done: Analysis Group. A.J. Brnabic: Eli Lilly & Company. I. Lipkovich: Eli Lilly & Company. Z. Kadziola: Eli Lilly & Company. A. Zion: Analysis Group. J.P. Dunn: Eli Lilly & Company. U. Desai: Analysis Group. N. Kirson: Analysis Group. G.K. Dimitriadis: Eli Lilly & Company. H. Kan: Eli Lilly & Company. Objective: To compare on-treatment weight reduction after 6 months among adults with obesity and without diabetes receiving tirzepatide (TZP) or semaglutide (SEMA) indicated for weight management in US clinical practice settings. Results are contextualized with clinical trials of SURMOUNT-1 (mean % weight reduction with TZP 5, 10, and 15 mg at 24 weeks was approximately 11%, 14%, and 15%, respectively) and STEP-1 (approximately 11% with SEMA 2.4 mg). Methods: This retrospective cohort study used Truveta electronic health records database linked with drug dispensing information from US healthcare systems (12/13/2024 data cut). Adults with a body mass index (BMI) of ≥30 kg/m2 or BMI ≥27 and <30 kg/m2 with ≥1 weight-related complication initiating TZP or SEMA between December 2023 and July 2024 (first dispense defined as index date) were included. Lack of prior use of glucagon-like peptide-1 receptor agonists and bariatric surgery, available weight records at index and at 6 months, and adherence to initial treatment during the 6-month follow-up (proportion of days covered ≥80%) were required. On-treatment weight changes from index to 6 months were assessed, including mean % weight change and proportion of patients achieving ≥5%, ≥10%, ≥15%, and ≥20% weight reduction. Weight change % was estimated using weighted linear regression model, with propensity score (PS) weights estimated from a generalized boosted model adjusting for baseline demographic, clinical, and socioeconomic factors. Binary outcomes were assessed with logistic regression using the same PS weights. Results are reported as adjusted means, proportions, mean differences, and odds ratios (OR) with 95% confidence intervals (CI). Results: 1,003 TZP and 1,393 SEMA-treated patients were included, with a mean (SD) age of 48.4 (12.2) and 49.1 (11.9) years, 69.9% and 73.2% female, mean (SD) BMI of 38.3 (7.2) and 38.4 (7.1) kg/m2, respectively. Adjusted mean 6-month % weight change (95% CI) was -11.2% (-11.8%, -10.5%) and -8.8% (-9.3%, -8.3%) in patients treated with TZP and SEMA, respectively, with TZP patients showing a greater mean weight reduction of 2.3 percent points (1.5, 3.2). A greater proportion of TZP patients, compared to SEMA, achieved weight reductions of: ≥5% (86.9% [84.6%, 88.8%] vs. 76.5% [73.9%, 78.9%], OR = 2.0 [1.6, 2.5]); ≥10% (59.6% [56.4%, 62.6%] vs. 37.5% [34.7%, 40.4%], OR = 2.5 [2.1, 2.9]); ≥15% (30.8% [27.9%, 33.8%] vs. 13.4% [11.5%, 15.5%], OR = 2.9 [2.3, 3.6]); ≥20% (11.3% [9.5%, 13.5%] vs. 3.8% [2.8%, 5.1%], OR = 3.2 [2.3, 4.6]). Conclusion: Among adults with obesity and without diabetes, TZP treatment in the real world was associated with significantly greater % weight reduction and greater proportion of patients achieving ≥5%, ≥10%, ≥15%, and ≥20% weight reduction compared to SEMA at 6 months. Further research is needed to assess weight reduction when TZP and SEMA achieve peak effectiveness beyond 6 months. Presentation: Saturday, July 12, 2025