Those taking Eli Lilly's obesity drug Zepbound lost nearly 50% more than those using rival Novo Nordisk's Wegovy in their first head-to-head study of the blockbuster drug.
Clinical trial participants who took tilzepatide, sold as Zepbound, lost an average of 50 pounds in 72 weeks, but who took semaglutide or Wegovy, or about 33 pounds (15 kilograms). That's according to a Lily-funded study published in the New England Journal of Medicine on Sunday.
Both medications are part of a new class of medications that work by mimicking gut and brain hormones that regulate appetite and bloating. However, tilzepatide targets two hormones known as GLP-1 and GIP, while Semaglutide targets GLP-1 only, says Dr. Louis Aronne, director of Weill Cornell Medicine's comprehensive weight control center.
“When two drugs come together, they can cause better weight loss,” Aronne said.
Tilzepatide won by Aronne saying many views as “effective drug races,” but both are important tools for treating obesity, which affects about 40% of American adults.
“The key to these drugs is to improve your health,” he said. “The majority of people don't need the most effective medicine.”
The trial included 751 people across the United States who had overweight, obesity and at least one weight-related health issue, but not diabetes. Participants received weekly injections of the highest tolerated Zepbound of either 10 or 15 milligrams or Wegovy, 1.7 or 2.4 milligrams of Zepbound.
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By the end of the trial, people who took Zepbound lost about 20% of their body weight on average, compared to nearly 14% losses of those who took Wegovy. The tilzepatide group was trimmed approximately 7 inches (17.8 cm) from the waist circumference, compared to approximately 5 inches (12.7 cm) with semaglutide. Additionally, almost 32% of people taking Zepbound lost at least a quarter of their body weight, compared to about 16% of people taking Wegovy.
The authors found that weight loss was approximately 6% lower in men than in women in both groups. Participants in both groups lost more weight, resulting in improved health markers such as blood pressure, blood fat, and blood glucose levels.
Over three-quarters of patients taking both medications reported at least one side effect. This is mild to moderate gastrointestinal problems such as nausea, constipation, diarrhea, and vomiting. Approximately 6% of participants taking Zepbound left the trial due to an adverse event, compared to 8% of those taking semaglutide.
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According to a 2024 survey by KFF, an independent health policy research organization, GLP-1 drugs are increasingly popular, with at least one in eight adults in the US reporting their use. Zepbound generated global sales of $4.9 billion last year. Wegovy has brought close to $8.8 billion (58.2 Danish Kroner).
Access and affordability limits the wider use of drugs. Tilzepatide and semaglutide were recently removed from the US Food and Drug Administration's list of drug shortages. Both manufacturers have recently released programs that reduce costs to less than about $500 a month, depending on the dose.
Other factors can affect access. This week, CVS Health said Wegovy will become a priority option on the standard prescription or list of eligible drugs as of July 1st. Zepbounds are excluded.
Dr. Angela Fitch, chief medical officer at obesity care company Candewell, has a variety of drugs to help spread the disease as obese in the United States. Wegovy is known to reduce the risk of serious heart problems by 20%, she noted. The medication may work well for one patient, but for the other patients.
“We need to use them all just because there are so many patients who need treatment,” she added.
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