INDIANAPOLIS, Indiana: Eli Lilly’s obesity drug Zepbound led to nearly 50 percent more weight loss than Novo Nordisk’s Wegovy in the first direct comparison of the two blockbuster medications, according to a study published over the weekend in the New England Journal of Medicine.

In the 72-week clinical trial, participants taking Zepbound (tirzepatide) lost an average of 50 pounds (22.8 kilograms), while those on Wegovy (semaglutide) lost about 33 pounds (15 kilograms). The trial, funded by Lilly, involved 751 overweight or obese participants in the U.S. who did not have diabetes but had at least one other weight-related health condition.

Zepbound, which targets two hormones — GLP-1 and GIP — that regulate appetite and feelings of fullness, appeared to be more effective than Wegovy, which only targets GLP-1, 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 at the European Congress on Obesity in Spain.

By the end of the trial, those taking Zepbound lost an average of 20 percent of their body weight, compared to a nearly 14 percent loss in the Wegovy group. The Zepbound group also reduced their waist circumference by about 7 inches (17.8 centimeters), compared to a 5-inch (12.7 centimeters) reduction among those taking Wegovy.

Additionally, nearly 32 percent of those on Zepbound lost at least 25 percent of their body weight, compared to 16 percent of those taking Wegovy. Weight loss was about 6 percent lower in men than in women in both groups, the study noted.

Both drugs produced similar side effects, primarily mild to moderate gastrointestinal issues like nausea, diarrhea, and vomiting. Approximately six percent of Zepbound users dropped out of the study due to adverse events, compared to eight percent of those taking Wegovy.

The GLP-1 drugs have seen a surge in popularity, with at least one in eight U.S. adults using them, according to a 2024 survey by KFF, a health policy research group. Last year, Zepbound generated US$4.9 billion in global sales, while Wegovy brought in $8.8 billion.

However, access and affordability remain challenges. The U.S. Food and Drug Administration recently removed both drugs from its list of shortages. The manufacturers have since launched programs to reduce costs to around $500 per month, depending on dosage.

Insurance coverage also varies. CVS Health recently announced that Wegovy will become the preferred drug for weight loss on its standard formulary starting July 1, excluding Zepbound.

Dr. Angela Fitch, chief medical officer of obesity care company knownwell, emphasized the need for multiple treatment options given the prevalence of obesity. “We’re going to need to use them all just because we have so many patients who need treatment,” she said, noting that Wegovy has been shown to cut the risk of serious heart problems by 20 percent.