Tirzepatide Demonstrates Greater Weight Loss Than Semaglutide in Head-to-Head Study
Full results from the SURMOUNT-5 trial showed tirzepatide achieved 20.2% mean weight loss vs 13.7% with semaglutide in adults with obesity or overweight.
Louis J. Aronne, MD
Photo courtesy of Weill Cornell Medical College
In the phase 3b SURMOUNT-5 trial, tirzepatide (Zepbound) demonstrated significantly greater weight loss compared with semaglutide (Wegovy) in adults with obesity or overweight with at least one weight-related comorbidity and without diabetes. The full results, presented at the 32nd European Congress on Obesity and simultaneously published in The New England Journal of Medicine, confirm the dual GIP/GLP-1 receptor agonist's superiority over the GLP-1 receptor agonist across multiple efficacy measures.1,2
Results showed that over 72 weeks, participants receiving tirzepatide achieved a mean body weight reduction of 20.2% compared to 13.7% for those who received semaglutide—a relative difference of 47% (22.8 kg vs 15.0 kg, respectively). Additionally, a higher proportion of tirzepatide-treated participants reached weight loss thresholds of ≥10% (81.6% vs 60.5%), ≥15% (64.6% vs 40.1%), ≥20% (48.4% vs 27.3%), and ≥25% (31.6% vs 16.1%) compared with those receiving semaglutide. Mean waist circumference reduction was also greater with tirzepatide (−18.4 cm vs −13.0 cm).1,2
"Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before," Louis J. Aronne, MD, principal investigator and director of the Comprehensive Weight Control Center at Weill Cornell Medicine, said in a press release.1 “"The SURMOUNT-5 head-to-head results demonstrated tirzepatide led to greater weight reduction compared to semaglutide, providing further evidence to support tirzepatide as an effective option for obesity management."
The open-label trial randomized 751 participants in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg). Both groups received lifestyle counseling. The safety profile of tirzepatide in this trial was consistent with earlier SURMOUNT studies, with primarily gastrointestinal-related adverse events reported. Treatment discontinuation due to adverse events occurred in 6.1% of tirzepatide recipients and 8.0% of semaglutide recipients. However, the study was not powered to compare safety outcomes between treatments.1,2
"In the SURMOUNT-5 trial, Zepbound demonstrated a significantly higher magnitude of weight reduction compared to Wegovy across all comparisons," Leonard Glass, MD, senior vice president, global medical affairs, Eli Lilly,” said in the May 11, 2025, press release.1 "These data confirm Zepbound as a leading treatment option for people living with obesity and equip healthcare providers with critical insights to make well-informed treatment decisions as part of a comprehensive obesity care plan."
Tirzepatide is approved in the US as Zepbound for chronic weight management and as Mounjaro for type 2 diabetes. Studies evaluating tirzepatide in chronic kidney disease and obesity-related morbidity and mortality are ongoing.1
References:
1. Zepbound (tirzepatide) showed superior weight loss over Wegovy (semaglutide) in complete SURMOUNT-5 results published in The New England Journal of Medicine. News release. Eli Lilly. May 11, 2025. Accessed May 12, 2025. https://investor.lilly.com/news-releases/news-release-details/zepbound-tirzepatide-showed-superior-weight-loss-over-wegovy
2. Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. NEJM. Published online May 11, 2025. doi:10.1056/NEJMoa2416394
