Zepbound beats Wegovy for weight loss in first head-to-head trial of
blockbuster drugs
[May 12, 2025]
By JONEL ALECCIA
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.
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Boxes for the medications Wegovy and Zepbound are arranged for a
photograph in California on Thursday, May 8, 2025. (AP Photo/JoNel
Aleccia)
 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.
___
AP Health Writer Tom Murphy in Indianapolis contributed to this
report.
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