231-OR: Differences in Weight Reduction Efficacy of Tirzepatide in Adults Without vs. With Type 2 Diabetes with Overweight or Obesity in SURMOUNT 1 and 2

Tirzepatide (TZP), a once-weekly GIP and GLP-1 receptor agonist approved in the US for treatment of type 2 diabetes and obesity, led to significant weight reduction (WR) in participants with overweight or obesity without type 2 diabetes (T2D, SURMOUNT (SM)-1) or with T2D (SM-2). Reasons behind higher WR efficacy with obesity treatment observed in people without T2D compared to people with T2D are unknown. We estimated the WR efficacy with TZP in SM-1 vs SM-2 after matching key baseline characteristics. Propensity score matching was used to create a balanced cohort of participants from SM-1 (excluding TZP 5 mg) and SM-2 (excluding those on sulfonylurea or pioglitazone), matched by age, gender, weight, BMI, antidepressant use or depression, and obesity-related comorbidities (ORCs). MMRM was performed to compare the percent of WR at Week 72 between the groups. At baseline, SM-2 cohort was on average older with more males, lower weight, higher HbA1c and higher comorbidity burden, compared to SM-1. The differences in WR remained after balancing baseline characteristics in the propensity matched sample (mean age 51.6 vs 53.9 yrs, females 55% vs 55%, weight 103.3 vs 99.5 kg and ≥2 ORCs 85% vs 85%) (FIG). The differences in WR efficacy with TZP between the SM-1 and SM-2 studies persisted after matching key baseline characteristics suggesting additional contributing factors. Disclosure R.J. Galindo: Consultant; Abbott. Other Relationship; Dexcom, Inc. Consultant; Bayer Inc. Other Relationship; Novo Nordisk, Eli Lilly and Company. Consultant; Boehringer-Ingelheim, AstraZeneca. W. Garvey: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Boehringer-Ingelheim, Inogen, Zealand Pharma A/S, Alnylam Pharmaceuticals, Inc., Pfizer Inc., Merck Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens, Pfizer Inc. Consultant; Boehringer-Ingelheim, Eli Lilly and Company. L.M. Neff: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Stefanski: Employee; Eli Lilly and Company. D. Cao: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company