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 & Co., Inc., Fractyl Health, Inc., Allurion. Research Support; 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

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.