815-P: Performance of Previously Identified Predictors of =15% Body Weight Reduction with Tirzepatide in Participants with Type 2 Diabetes in SURMOUNT-2

Introduction and Objective: In SURPASS-1-4 (SP), baseline factors associated with higher likelihood of achieving body weight (BW) reduction ≥15% at WK 40/42 with tirzepatide (TZP) in participants with T2D were: higher TZP dose, female sex, White or Asian race, metformin use, better glycemic status and lower non-HDL-C. We assessed performance of these predictors in BW reduction ≥15% at WK 48 in SURMOUNT-2 (SM-2), a study of TZP in chronic weight management in adults with T2D with obesity or overweight. Methods: The multivariate model from SP was run in SM-2 participants who were on TZP at WK 48, ≥75% compliance and no rescue medication during the study treatment period. The AUC (area under curve) of the SM-2 model was calculated to determine its accuracy. Results: BW reduction ≥15% was achieved in 41.8% (n = 230) participants on TZP at WK 48 and 91.3% (n = 210) sustained BW reduction ≥15% at WK 72. Factors identified in SP that were replicated with respect to the estimated effect size in SM-2: higher TZP dose, female, and lower HbA1c, FSG and non-HDL-C (Table 1). In SM-2, unlike in SP, Asian race and metformin use were not positively associated with BW reduction ≥15%. The AUC was 65.6%. Conclusion: In the current study there are some consistencies in SM- 2 when applying the SP model. However, the overall performance of the predictors of the model demonstrates a need for refinement. Disclosure I. Lingvay: Consultant; Altimmune, Astra Zeneca, Bayer, Biomea, Boehringer-Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J NovoNordisk, Sanofi, Mylan, Boehringer-Ingelheim. Consultant; TERNS Pharma, The Comm Group, Valeritas, WebMD, and Zealand Pharma. M. Malecki: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott, Dexcom, Inc., Boehringer-Ingelheim. Speaker's Bureau; AstraZeneca, Merck Krka. Speaker's Bureau; Servier Laboratories. I. Benabbad: Employee; Eli Lilly and Company. B. Falcon: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company, Sangamo Therapeutics. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Wang: None. J.P. Dunn: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company