Zepbound beats Wegovy for weight loss in first head-to-head trial of blockbuster drugs

People taking Eli Lilly’s obesity drug, Zepbound, lost nearly 50% more weight than those using rival Novo Nordisk’s Wegovy in the first head-to-head study of the blockbuster medications.

Clinical trial participants who took tirzepatide, the drug sold as Zepbound, lost an average of 50 pounds (22.8 kilograms) over 72 weeks, while those who took semaglutide, or Wegovy, lost about 33 pounds (15 kilograms). That’s according to the study funded by Lilly, which was published Sunday in the New England Journal of Medicine.

Both drugs are part of a new class of medications that work by mimicking hormones in the gut and brain that regulate appetite and feelings of fullness. But tirzepatide targets two such hormones, known as GLP-1 and GIP, while semaglutide targets GLP-1 alone, said Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine.

“Two drugs together can produce better weight loss,” said Aronne, who led the study and presented the findings Sunday at the European Congress on Obesity in Spain.

While tirzepatide won out in what Aronne said many view as “a drag race of efficacy,” both are important tools for treating obesity, which affects about 40% of American adults.

“The point of these medications is to improve health,” he said. “The majority of people won’t need the most effective medication.”

The trial included 751 people from across the U.S. who were overweight or had obesity and at least one other weight-related health problem, but not diabetes. Participants received weekly injections of the highest tolerated doses of Zepbound, either 10 milligrams or 15 milligrams, or Wegovy, 1.7 milligrams or 2.4 milligrams.

By the end of the trial, those who took Zepbound lost about 20% of their body weight on average, compared with a nearly 14% loss for those who took Wegovy. The tirzepatide group trimmed about 7 inches (17.8 centimeters) from their waist circumference, compared to about 5 inches (12.7 centimeters) with semaglutide. In addition, nearly 32% of people taking Zepbound lost at least a quarter of their body weight, compared to about 16% of those taking Wegovy, the study found.

Weight loss was about 6% lower in men than in women in both groups, the authors noted. As participants in both groups lost more weight, they saw improvements in health markers such as blood pressure, blood fat and blood sugar levels.

More than three-quarters of patients taking both drugs reported at least one side effect, mostly mild to moderate gastrointestinal issues such as nausea, constipation, diarrhea and vomiting. About 6% of participants taking Zepbound left the trial because of adverse events, compared with 8% of those taking semaglutide.

The GLP-1 drugs have become increasingly popular, with at least 1 in 8 U.S. adults reporting their use, according to a 2024 survey by KFF, a independent health policy research organization. Zepbound generated $4.9 billion in global sales last year. Wegovy brought in nearly $8.8 billion (58.2 billlion Danish kroner).

Access and affordability have limited wider use of the drugs. Tirzepatide and semaglutide were removed recently from a list of drug shortages by the U.S. Food and Drug Administration. Both manufacturers recently released programs that cut costs to about $500 per month or less, depending on the dose.

Other factors can affect access. This week, CVS Health said Wegovy will become the preferred option on its standard formulary, or list of covered drugs, as of July 1. Zepbound will be excluded.

It’s important to have a range of drugs to treat a disease as widespread as obesity in the U.S., said Dr. Angela Fitch, chief medical officer of knownwell, an obesity care company. Wegovy has been found to cut the risk of serious heart problems by 20%, she noted. A drug may work well for one patient, but not for others.

“We’re going to need to use them all just because we have so many patients who need treatment,” she added.

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AP Health Writer Tom Murphy in Indianapolis contributed to this report.

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