Eli Lilly’s Zepbound Achieves Superior Weight Loss Over Wegovy in SURMOUNT-5 Phase 3b Obesity Study

Eli Lilly released complete results from the SURMOUNT-5 Phase 3b trial, showing that Zepbound (tirzepatide) significantly outperformed Wegovy (semaglutide) in weight loss among adults with obesity or overweight with comorbidities but without diabetes. After 72 weeks, Zepbound users experienced an average weight reduction of 20.2%, compared to 13.7% with Wegovy, translating to 47% greater relative weight loss. These findings were presented at the 32nd European Congress on Obesity (ECO) and published in The New England Journal of Medicine. 

"In the SURMOUNT-5 trial, Zepbound demonstrated a significantly higher weight reduction magnitude than Wegovy across all comparisons. 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," said Leonard Glass, MD, FACE, senior vice president, global medical affairs, Lilly.

Beyond the primary endpoint, Zepbound showed superiority across all five key secondary endpoints. Notably, 64.6% of patients treated with Zepbound achieved ≥15% weight loss, compared to 40.1% for Wegovy. Average weight loss for Zepbound was 50.3 lbs (22.8 kg) versus 33.1 lbs (15.0 kg) for Wegovy. Zepbound also led to a greater waist circumference reduction—7.2 inches versus 5.1 inches for Wegovy.

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, an internist specialising in diabetes and obesity at New York-Presbyterian/Weill Cornell Medical Center, and principal investigator of SURMOUNT-5, commented, "Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before. The SURMOUNT-5 head-to-head results demonstrated that tirzepatide led to greater weight reduction than semaglutide, providing further evidence to support tirzepatide as an effective option for obesity management."

Regarding safety, adverse events were primarily gastrointestinal, mostly mild to moderate, and consistent with prior Zepbound studies. Fewer participants discontinued Zepbound due to side effects (6.1%) than Wegovy (8.0%). However, the trial was not designed to compare the safety of the two drugs directly. Zepbound (tirzepatide) is marketed in the U.S. for obesity and under the brand name Mounjaro for type 2 diabetes globally.