Individuals on Eli Lilly’s weight-loss drug, Zepbound, lost almost 50% more weight than those on competitor Novo Nordisk’s Wegovy in the first head-to-head trial of the blockbuster drugs.
Participants in clinical trials who received tirzepatide, the medication marketed as Zepbound, lost 50 pounds (22.8 kilograms) on average over 72 weeks, compared with those receiving semaglutide, or Wegovy, who lost approximately 33 pounds (15 kilograms). That’s what the Lilly-funded study, published Sunday in the New England Journal of Medicine, found.
Both medications belong to a new generation of drugs that operate by imitating hormones in the brain and intestines that suppress appetite and sensation of fullness. But tirzepatide acts on two such hormones, GLP-1 and GIP, whereas semaglutide acts on GLP-1 alone, according to Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine.
Two medications combined can cause greater weight loss,” Aronne said, leading the research and reporting Sunday at the European Congress on Obesity in Spain.
Though tirzepatide emerged victorious in what Aronne described as “a drag race of efficacy,” both are valuable weapons against obesity, which is found in around 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 study involved 751 overweight or obese people from all over the U.S. with at least one other weight-related medical condition but not diabetes. Participants got weekly injections of the highest dose tolerated of Zepbound, either 10 milligrams or 15 milligrams, or Wegovy, 1.7 milligrams or 2.4 milligrams.
At the conclusion of the trial, those on Zepbound lost approximately 20% of their body weight on average, while the group taking Wegovy lost nearly 14%. The tirzepatide group lost around 7 inches (17.8 centimeters) of their waistline, versus around 5 inches (12.7 centimeters) for semaglutide. Also, almost 32% of Zepbound takers lost more than a quarter of their body weight compared to roughly 16% of Wegovy users, according to the study.
Both men and women achieved about 6% less weight loss in each group, the authors wrote. The more weight that people in each group lost, the greater the improvements in health indicators like blood pressure, blood fat and blood sugar, the authors found.
Over three-quarters of patients on both medications had at least one side effect, primarily mild to moderate gastrointestinal symptoms like diarrhea, vomiting, constipation and nausea. Around 6% of participants on Zepbound dropped out of the trial due to adverse events compared with 8% of participants on semaglutide.
The GLP-1 medications have grown to be more in vogue, with at least 1 out of every 8 U.S. adults claiming to use them, a KFF survey reported in 2024. Zepbound achieved $4.9 billion in global sales during the last year. Wegovy recorded almost $8.8 billion (58.2 billlion Danish kroner).
Affordability and access have restricted broader use of the drugs. Tirzepatide and semaglutide have recently been delisted from a shortage of drugs by the U.S. Food and Drug Administration. Both companies recently introduced programs that reduced the costs to around $500 monthly or lower, depending on the dose.
Other considerations may influence access. This week, CVS Health announced Wegovy will be the preferred choice on its standard formulary, or list of covered medications, as of July 1. Zepbound will be excluded.
Having multiple drugs to address a disease as prevalent as obesity in the U.S. is crucial, said Dr. Angela Fitch, chief medical officer of knownwell, an obesity care firm. Wegovy has been shown to reduce the risk of severe heart issues by 20%, she added. A medication can be effective for one patient but not for others.
We’re going to have to utilize all of them just because we have so many patients that need to be treated,” she said