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Zepbound Outperforms Wegovy in Head-to-Head Weight Loss Study

By I. Edwards HealthDay Reporter

Medically reviewed by Carmen Pope, BPharm. Last updated on May 12, 2025.

MONDAY, May 12, 2025 — A new study has found that people taking Eli Lilly’s obesity drug Zepbound lost almost 50% more weight than those using Novo Nordisk’s Wegovy.

The study — published May 11 in the New England Journal of Medicine — followed 751 people across the U.S. who were overweight or obese and had another weight-related health problem. None had diabetes, The Associated Press reported.

Participants received weekly injections of either Zepbound (tirzepatide) or Wegovy (semaglutide).

After 72 weeks, people taking Zepbound lost an average of 50 pounds. Those on Wegovy lost about 33 pounds. That translated to a loss of about 20% of body weight for Zepbound users, compared to nearly 14% for Wegovy users.

What's more, waist size also shrank by an average of 7 inches with Zepbound and about 5 inches with Wegovy.

The medications work by mimicking hormones that help regulate appetite and fullness. Zepbound targets two hormones (GLP-1 and GIP), while Wegovy targets only GLP-1, AP reported.

“Two drugs together can produce better weight loss,” said lead study author Dr. Louis Aronne of Weill Cornell Medicine. He presented the results Sunday at the European Congress on Obesity in Malaga, Spain.

Nearly 32% of Zepbound users lost at least a quarter of their body weight, compared with about 16% of Wegovy users. In both groups, weight loss was about 6% lower in men than in women, AP said.

Both groups saw health improvements in blood pressure, blood sugar and blood fat levels, too.

About three-quarters of study participants reported mild or moderate stomach issues, including nausea, constipation, diarrhea or vomiting.

In all, around 6% of Zepbound users and 8% of Wegovy users left the trial due to side effects, AP said in a report.

The drugs are popular. A 2024 KFF survey found that about 1 in 8 U.S. adults has used one of these medications. Zepbound sales totaled $4.9 billion worldwide last year, while Wegovy earned nearly $8.8 billion.

Both drugs were recently removed from the U.S. Food and Drug Administration's shortage list. Drugmakers have introduced programs to lower patient costs to $500 or less per month.

However, CVS Health recently announced that Wegovy will be the preferred option on its list of covered drugs starting July 1, while Zepbound won't be.

“We’re going to need to use them all just because we have so many patients who need treatment,” Dr. Angela Fitch, chief medical officer of knownwell, an obesity care company, said.

She noted Wegovy has also been shown to cut the risk of serious heart problems by 20%.

The study was funded by Eli Lilly, maker of Zepbound.

Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions.

© 2025 HealthDay. All rights reserved.

Posted May 2025

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