Zepbound Beats Wegovy for Weight Loss: Should You Switch?
A direct comparison of two popular weight-loss medications, Zepbound and Wegovy, has revealed that Zepbound led to significantly more weight loss in study participants. The clinical trial, funded by Zepbound’s manufacturer, Eli Lilly, and published in the New England Journal of Medicine, found that individuals taking Zepbound lost an average of 50 pounds (22.8 kilograms) over 72 weeks. In contrast, those taking Wegovy, produced by Novo Nordisk, experienced an average weight loss of 33 pounds (15 kilograms).
Both Zepbound (tirzepatide) and Wegovy (semaglutide) belong to a class of drugs that mimic gut and brain hormones to regulate appetite and promote feelings of fullness. However, Zepbound uniquely targets two of these hormones – GLP-1 and GIP – while Wegovy targets only one (GLP-1). Dr. Louis Aronne, the study’s lead author and director of the Comprehensive Weight Control Center at Weill Cornell Medicine, explained that targeting multiple hormones can lead to greater weight loss.
The trial involved 751 participants across the U.S. who were overweight or obese and had at least one other weight-related health issue, excluding diabetes. Participants received weekly injections of the highest tolerated doses of either Zepbound (10 mg or 15 mg) or Wegovy (1.7 mg or 2.4 mg).
By the end of the 72-week study, the Zepbound group achieved an average 20% reduction in body weight, significantly higher than the nearly 14% average weight loss seen in the Wegovy group. The Zepbound participants also saw a greater reduction in waist circumference, losing about 7 inches (17.8 centimeters) compared to approximately 5 inches (12.7 centimeters) with Wegovy. Notably, almost 32% of those on Zepbound lost at least 25% of their body weight, double the rate of the Wegovy group (around 16%).
The study authors observed that weight loss was about 6% lower in men compared to women in both treatment groups. As participants lost weight with both medications, they experienced improvements in key health markers like blood pressure, blood fat levels, and blood sugar.
The majority of participants in both groups (over 75%) reported at least one side effect, primarily mild to moderate gastrointestinal issues such as nausea, constipation, diarrhea, and vomiting. Discontinuation of the trial due to adverse events was slightly lower in the Zepbound group (6%) compared to the Wegovy group (8%).
These GLP-1 drugs have gained significant popularity, with a recent survey indicating that at least 1 in 8 U.S. adults have used them. In terms of sales, Zepbound generated $4.9 billion globally last year, while Wegovy brought in nearly $8.8 billion. While access and affordability have been challenges, both manufacturers have recently introduced programs to reduce monthly costs to around $500 or less, depending on the dosage. However, formulary decisions by insurance providers, such as CVS Health’s recent announcement making Wegovy the preferred option, will continue to influence patient access.
Experts like Dr. Angela Fitch emphasize the importance of having a range of effective treatments for obesity, given its prevalence affecting approximately 40% of American adults. While Zepbound demonstrated greater weight loss in this head-to-head trial, both medications are valuable tools in managing obesity and improving patient health. Individual responses to these drugs can vary, and the most effective treatment will depend on individual patient needs.
Source: The New England Journal of Medicine, May 11 2025