Study suggests Zepbound outperforms Ozempic and Wegovy for weight loss

NBC News

Tirzepatide, the active ingredient in Eli Lilly’s Mounjaro and Zepbound drugs, is a more effective weight-loss drug than semaglutide in Ozempic and Novo Nordisk’s Wegovy, suggests a study published Monday in the journal JAMA Internal Medicine that is believed to be the first direct comparison between the two blockbuster weight-loss drugs.

Since Zepbound was approved for weight loss in late 2023, it seemed to have an advantage over Wegovy. Patients taking the highest dose of Zepbound lost 21% of their weight in 72 weeks, compared with 15% of those taking Wegovy after 68.

But it was difficult to make a direct comparison without a study looking at both drugs, which are part of a new class of medications called GLP-1.

“We’ve been tracking GLP-1 use over the last year and have seen some really dramatic increases, but there’s not a lot of data available for direct comparisons,” said Tricia Rodriguez, senior author of the study and chief scientist at Truveta Research, a healthcare analytics company.

In the new study, Rodriguez and colleagues analyzed the medical records of more than 41,000 overweight or obese adults who had been prescribed one of the two drugs for the first time. Participants were not excluded if they had type 2 diabetes. More than 9,100 were prescribed tirzepatide and more than 32,000 were prescribed semaglutide.

Researchers looked at the patients’ weight loss at 3, 6, and 12 months. People taking semaglutide lost, on average, 3.6% of their weight at 3 months, 5.8% at 6 months, and 8.3% at 12 months. People taking tirzepatide lost a greater percentage of their weight per month: 5.9% at 3 months; 10.1% at 6 months; and 15.3% at 1 year.

“Most patients taking both drugs experienced clinically significant weight loss, but those taking tirzepatide experienced significantly greater weight loss,” Rodriguez said.

Researchers found no major differences between the two drugs in the risk of serious side effects, such as gastroparesis, also known as stomach paralysis.

Semaglutide and tirzepatide work in a similar way. GLP-1 drugs mimic a hormone that helps reduce food intake and appetite. Tirzepatide also mimics a second hormone, GIP, which, as well as reducing appetite, is thought to improve the way the body breaks down sugar and fat.

Researchers will still need to conduct a randomized, controlled clinical trial to see which drug is truly the best. Last year, Lilly began a 700-patient Phase 3 trial comparing the two drugs. The trial is expected to end in November, according to

A Novo Nordisk spokesman said the new study had some “key limitations,” including the inclusion of patients with type 2 diabetes, who often have a harder time losing weight than people without the disease. The study also did not provide enough information about the doses patients started on and progressed to.

“While weight reduction is an important goal of obesity treatment, it is also vital to consider other needs when choosing a treatment,” the spokesperson said.

Eli Lilly did not immediately respond to a request for comment.

Susan Spratt, an endocrinologist and medical director of the Office of Population Health Management at Duke Health in North Carolina, said that while the study makes it clear that tirzepatide is more effective, both drugs are still good options for patients because they allow for more weight loss than other drugs available.

He also noted that more studies are needed comparing the effects on other health outcomes besides weight loss.

Semaglutide, for example, has been shown in trials to reduce the risk of cardiovascular problems—such as heart attack and stroke—in people who are overweight or obese, and the risk of complications from kidney disease in people with type 2 diabetes; tirzepatide has been shown to be a potential treatment for obstructive sleep apnea.

“That said, if someone’s primary goal is weight loss, I would probably go with tirzepatide,” Spratt said.

Daniel Maselli, a physician specializing in obesity medicine at True You Weight Loss, a weight-loss clinic in Atlanta, Georgia, said the study supports previous research that has shown tirzepatide results in greater weight loss than semaglutide.

While this is important information for doctors, he noted that weight loss alone is not the only factor they consider when prescribing weight-loss drugs to patients.

It also takes into account the patient’s goals, medical needs, such as improving heart health, and tolerance to certain medications. Some patients, for example, do not tolerate tirzepatide well but lose weight on semaglutide.

“This study helped address the weight loss component, but as the authors note, it was limited in discerning differences in tolerability, safety, or improvements in obesity complications,” he wrote in an email.