Eli Lilly’s Zepbound Demonstrates Superior Weight Loss to Wegovy in Adults With Obesity or Overweight

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Data from the Phase IIIb SURMOUNT-5 clinical trial found that Eli Lilly’s Zepbound (tirzepatide) demonstrated superior weight loss compared to Wegovy (semaglutide) in adults with obesity or overweight and at least one weight-related medical condition. According to the company, the study met its primary endpoint and all five key secondary endpoints. Lilly intends to continue to evaluate the SURMOUNT-5 results, which will be published in a peer-reviewed journal and presented at a medical meeting next year.¹

"Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice," said Leonard C. Glass, MD, FACE, SVP, global medical affairs, Lilly Cardiometabolic Health, in a press release. "We are thrilled that today's findings showed the superior weight loss of Zepbound, which helped patients achieve 47% more relative weight loss compared to Wegovy. Zepbound is in a class of its own as the only FDA-approved dual GIP and GLP-1 receptor agonist obesity medication, and it's changing how millions of people manage this chronic disease."

The multi-center, randomized, open-label SURMOUNT-5 trial enrolled adults with obesity or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease who did not have diabetes. The trial included 751 patients across the United States and Puerto Rico, who were randomly assigned in a 1:1 ratio to receive maximum tolerated dose of Zepbound (10 mg or 15 mg) or Wegovy (1.7 mg or 2.4 mg). The primary endpoint of the study was to demonstrate Zepbound's superiority in percent change from baseline in body weight at 72 weeks compared to Wegovy.

Results found that Zepbound achieved an average weight loss of 20.2% compared to 13.7% for Wegovy. Additionally, 31.6% of Zepbound users achieved at least a 25% body weight reduction compared to 16.1% on Wegovy.

Lilly stated that common adverse events (AEs) associated with both Zepbound and Wegovy were gastrointestinal-related and generally mild to moderate in severity. Other AEs include kidney failure, stomach issues, gallbladder issues, pancreatitis, hypoglycemia, changes in vision in patients with type 2 diabetes, depression, and thoughts of suicide. The most frequently reported AEs in the trial include nausea, diarrhea, vomiting, constipation, stomach pain, indigestion, injection site reactions, feeling tired, allergic reactions, belching, hair loss, and heartburn. The overall safety profile of Zepbound in SURMOUNT-5 was found to be similar to previously reported SURMOUNT trials. Lilly warns against the use of Zepbound in patients that havemedullary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2, or a serious allergic reaction to tirzepatide or any of the ingredients in Zepbound. Additionally, it may result in thyroid tumors.¹

According to the Centers for Disease Control and Prevention, between 2021 and 2023, the prevalence of obesity in adults was 40.3% in the United States. Of those evaluated, 39.2% were men and 41.3% were women. The prevalence of obesity in adults aged 40–59 years was 46.4%, 35.5% in adults between 20 and 39 years of age, and 38.9% in adults over 60 years of age. Additionally, the prevalence of severe obesity is 9.4%, with women experiencing higher numbers than men in each age group. Further, the prevalence of obesity in adults remains above the Healthy People 2030 goal of 36.0%.²

Zepbound was first approved by the FDA on November 8, 2023, for adults with obesity or with excess weight and weight-related medical problems.¹

References

1. Lilly's Zepbound® (tirzepatide) superior to Wegovy® (semaglutide) in head-to-head trial showing an average weight loss of 20.2% vs. 13.7%. Lilly. December 4, 2024. Accessed December 4, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head

2. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021–August 2023. CDC. Accessed December 4, 2024. https://www.cdc.gov/nchs/products/databriefs/db508.htm