SAT-736 Post-hoc analysis of weight reduction and physical function in participants with obesity or overweight and osteoarthritis in SURMOUNT-1

Abstract Disclosure: T.J. Schnitzer: Eli Lilly & Company, Pfizer, Inc., GlaxoSmithKline, IBSA, Tremeau, Tremeau, Paradigm, Techfields, AstraZeneca, Regeneron Pharmaceuticals, Novartis Pharmaceuticals, Amgen Inc, Taiwan Liposome Company, Vertex, KolonTissueGene, Paradigm, Techfields. H. Hoffman: Eli Lilly & Company. J. Brumm: Eli Lilly & Company. T.D. Forrester: Eli Lilly & Company. R. Mody: Eli Lilly & Company. B. Falcon: Eli Lilly & Company. A. Zakharyan: Eli Lilly & Company. T.M. Gibble: Eli Lilly & Company. Introduction: Treatment with tirzepatide (TZP), a once-weekly dual GIP/GLP-1 receptor agonist, resulted in substantial body weight reduction (16.0-22.5%) compared to placebo (2.4%) in participants with obesity or overweight, without diabetes, in SURMOUNT-1 (SM-1). This post-hoc analysis investigated weight reduction and changes in physical function with TZP treatment in participants with osteoarthritis (OA) at baseline. Methods: SM-1 participants with OA (MedDRA preferred terms osteoarthritis or spinal osteoarthritis) at baseline were included in this analysis (N=268). Weight change (%) from baseline to Week 72 was calculated using the modified intent-to-treat efficacy analysis set (all randomized and treated participants, excluding off-treatment data). Participants treated with different doses of TZP were pooled and analyzed for least square mean change from baseline to Week 72 (LOCF) in the IWQOL-Lite-CT physical function composite scores and norm-based SF-36v2 physical functioning scores by weight reduction targets. Results: Participants with OA at baseline had a mean age of 57 years, weight of 104 kg, BMI of 38.0, waist circumference of 115 cm, duration of obesity of 19.8 years, and 75.3% were female. At week 72, participants with OA treated with TZP displayed a dose-dependent reduction in body weight from baseline, with weight reductions of -3.3% with placebo, and -16.3%, -21.5%, and -22.3% (all doses p<0.001 vs placebo) with TZP 5mg, 10mg, and 15 mg, respectively. Of the pooled TZP treated participants with OA at baseline, those that achieved greater weight reduction targets had larger improvements to both IWQOL-Lite-CT physical function composite scores and SF-36v2 physical functioning scores at week 72. Improvements to mean IWQOL-Lite-CT physical function composite scores of 20.7 (SE: 1.5), 23.2 (1.6), 23.6 (1.8), 24.7 (2.1), and 25.7 (2.4) were observed in participants that achieved weight reduction of ≥5%, ≥10%, ≥15%, ≥20%, ≥25%, respectively. Furthermore, improvements to SF-36v2 physical functioning scores of 5.1 (0.5), 5.7 (0.5), 5.8 (0.6), 5.9 (0.6), and 6.3 (0.8) were observed in participants that achieved weight reduction of ≥5%, ≥10%, ≥15%, ≥20%, ≥25%, respectively. Conclusion: In this post-hoc analysis, greater weight reduction was associated with increasing doses of TZP among SM-1 participants with OA at baseline, similar to the reductions seen in the overall SM-1 population. Furthermore, for participants with OA at baseline, greater reductions in weight were associated with greater improvements in physical functioning scores. Presentation: Saturday, July 12, 2025