N Engl J Med

SURMOUNT-5: Tirzepatide outperforms semaglutide in obesity treatment

May 13, 2025

Treatment with tirzepatide was superior to semaglutide in reducing body weight and waist circumference at week 72. These findings could influence treatment protocols and enhance patient outcomes in obesity care.

Study details: The phase 3b SURMOUNT-5 trial (NCT05822830) compared the efficacy of tirzepatide (Zepbound) and semaglutide (Wegovy) in adults with obesity or overweight and comorbidities. The trial included a diverse group of 751 participants with obesity but without T2DM who were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg) SC weekly. Percent change in weight from baseline to week 72 was the primary endpoint. Key secondary endpoints included weight reductions of at least 10%, 15%, 20%, and 25% and a change in waist circumference from baseline to week 72.

Results: Tirzepatide resulted in significantly greater weight loss at 72 weeks compared with semaglutide. At the highest dose (15 mg), tirzepatide achieved a mean weight reduction of 20.2% vs. 13.7% with semaglutide. Additionally, a higher proportion of participants on tirzepatide achieved weight reductions of 10%, 15%, 20% and 25%. GI adverse events were common in both groups but were generally mild to moderate in severity.

Source:

Aronne LJ, et al; SURMOUNT-5 Trial Investigators. (2025, May 11). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. https://pubmed.ncbi.nlm.nih.gov/40353578/