Zepbound vs. Wegovy: Latest Clinical Trial Results
Participants achieved an average weight loss of 20.2% with Zepbound vs. 13.7% with Wegovy.
In key secondary endpoints, Zepbound was superior to Wegovy across all weight reduction targets and waist circumference reduction.
INDIANAPOLIS, May 11, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced detailed results from SURMOUNT-5, a Phase 3b open-label clinical trial evaluating the safety and efficacy of Zepbound (tirzepatide), a dual GIP and GLP-1 receptor agonist, compared to Wegovy (semaglutide), a mono GLP-1 receptor agonist, in adults living with obesity, or overweight with at least one weight-related medical problem and without diabetes. At 72 weeks, Zepbound met the primary endpoint and all five key secondary endpoints, demonstrating superiority compared to Wegovy across the trial. The detailed results were presented at the 32nd European Congress on Obesity (ECO) and simultaneously published in The New England Journal of Medicine.
Trial Findings
For the primary endpoint, participants treated with Zepbound achieved an average weight reduction of 20.2% compared to 13.7% with Wegovy at 72 weeks using the treatment-regimen estimand, a 47% greater relative weight loss. Participants using Zepbound lost an average of 50.3 lbs (22.8 kg) and participants on Wegovy lost an average of 33.1 lbs (15.0 kg).
Key Secondary Endpoints
In key secondary endpoints, Zepbound was superior across all weight reduction targets with 64.6% of participants treated with Zepbound achieving at least 15.0% weight loss compared to 40.1% on Wegovy. Additionally, participants treated with Zepbound achieved a superior average waist circumference reduction of 7.2 in (18.4 cm), while those treated with Wegovy saw an average reduction of 5.1 in (13.0 cm).
"Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before," said Louis J. Aronne, MD, FACP, DABOM, director of the Comprehensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine.
Primary and Key Secondary Endpoints
| Endpoint |
Zepbound (tirzepatide) |
Wegovy (semaglutide) |
| Avg % weight loss |
-20.2 % |
-13.7 % |
| Achieved ≥10% weight loss |
81.6 % |
60.5 % |
| Achieved ≥15% weight loss |
64.6 % |
40.1 % |
| Achieved ≥20% weight loss |
48.4 % |
27.3 % |
| Achieved ≥25% weight loss |
31.6 % |
16.1 % |
| Waist circumference reduction |
-18.4 cm |
-13.0 cm |
"In the SURMOUNT-5 trial, Zepbound demonstrated a significantly higher magnitude of weight reduction compared to Wegovy across all comparisons," said Leonard Glass, MD, FACE, senior vice president, global medical affairs, Lilly.
Safety Profile
The safety profile of Zepbound in SURMOUNT-5 was consistent with previous SURMOUNT trials. Adverse events reported during the trial were primarily gastrointestinal-related and were generally mild to moderate in severity.
During the trial, 6.1% of participants taking Zepbound discontinued treatment due to adverse events, compared to 8.0% of participants taking Wegovy.
About Zepbound and Tirzepatide
Tirzepatide is commercialized for adults with obesity or with overweight who also have weight-related medical problems as Zepbound in the U.S. and Mounjaro in some countries outside of the U.S. It is a once-weekly dual GIP and GLP-1 receptor agonist.
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