While both are safe and effective options for weight loss, in a head-to-head study, Zepbound beat out Wegovy, research found

Zepbound or Wegovy? Head-to-Head Trial Says One Is Better for Weight Loss

While both are safe and effective options for weight loss, in a head-to-head study, Zepbound beat out Wegovy, research found

In a head-to-head trial, Zepbound beat out Wegovy for weight loss, a clinical trial showed.
Experts say that both drugs are safe and effective options for treating obesity.
Though Zepbound led to greater weight loss, factors such as insurance coverage and secondary treatment indications can impact whether Zepbound or Wegovy is right for you.

With multiple safe and effective weight loss drugs on the market, how can you tell which one is best? New research may have an answer.

Eli Lilly’s Zepbound proved more effective than Novo Nordisk’s Wegovy in a new head-to-head trial, though both medications resulted in substantial weight loss.

The trial, called SURMOUNT-5, specifically found that participants with obesity who took tirzepatide (the active ingredient in Zepbound) had greater reductions in body weight and waist circumference than those who took semaglutide (the active ingredient in Wegovy).

“Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before,” Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine and principal investigator of the SURMOUNT-5 trial, said in a press release.

The SURMOUNT-5 data was first presented in December 2024 but was later peer-reviewed and published in the New England Journal of Medicine on May 11.

Which Injectable Drug Came Out On Top for Weight Loss?

The SURMOUNT-5 study recruited 751 adults who were overweight or obese. None of the participants had diabetes, though all had at least one other condition, including high blood pressure, obstructive sleep apnea, cardiovascular disease, or high cholesterol.

Researchers randomly assigned participants to take either Zepbound or Wegovy for 18 months.

At the end of the study, the results showed:

People taking Zepbound lost more body weight. Those on Zepbound lost 20.2% of their body weight (about 50 pounds on average), while participants on Wegovy lost 13.7% (about 33 pounds).
Zepbound led to a greater reduction in waist size. On average, participants lost 18.4 centimeters around their waist on Zepbound and 13 centimeters on Wegovy.

The majority of the participants, regardless of whether they were taking Zepbound or Wegovy, experienced at least one gastrointestinal side effect, such as nausea, diarrhea, constipation, or vomiting. Side effects were slightly more common in the Wegovy group—5.6% of people on Wegovy dropped out of the study early, as compared to 2.7% of people taking Zepbound.

Will These Results Hold Up in the Real World?

The SURMOUNT-5 results aren’t necessarily surprising, Avlin Imaeda, MD, PhD, associate professor of digestive diseases and North Haven Endoscopy Center medical director at the Yale School of Medicine, told Health.

A study published in July 2024 found that Mounjaro (another tirzepatide medication) outperformed Ozempic (semaglutide) for weight loss.

And because the trial participants were representative of the general population, you could expect to see the results hold up among weight loss drug users at large, added Meera Shah, MB ChB, an endocrinologist at the Mayo Clinic.

However, there are a few limitations. Shah told Health that the study had fewer participants than previous Zepbound trials, and only 80% of people completed the study. The trial was also not blinded, meaning participants and research staff knew who received Zepound or Wegovy, opening the door for potential bias.

Why Was Zepbound More Effective?

Dosing is one reason Zepbound why may have come out in this trial. The maximum tolerated dose used in the study for Zepbound was higher, 10 to 15 milligrams (mg), as compared to Wegovy’s 1.7 or 2.4 mg.

Drugmaker Novo Nordisk will present unpublished data later this year, showing that a higher dose of Wegovy, 7.2 mg, leads to more comparable weight loss.

Another possible explanation has to do with how Zepbound is formulated. Both Wegovy and Zepound are glucagon-like peptide-1 (GLP-1) agonist drugs, which means they stimulate insulin production, reduce appetite, and slow stomach emptying. But Zepound is also a gastric inhibitory polypeptide (GIP) agonist, which can further control blood sugar and stimulate weight loss.

Which Weight Loss Drug is Right For You?

This latest head-to-head trial provides important context for millions of Americans with obesity who are considering taking Zepbound or Wegovy. The number of people taking GLP-1 drugs to lose weight has increased 700% between 2019 and 2023, and about one in eight American adults have already reported trying a GLP-1 drug, with four in 10 reporting they took them primarily for weight loss.

So should you ask your doctor for Zepbound over Wegovy if you're looking to lose weight? Generally speaking, experts say yes.

“I typically would go to tirzepatide [Zepbound] first, both because it is better tolerated in my experience and it is more effective,” Imaeda said. “I do have patients who were on semaglutide [Wegovy] and [were] able to switch because their weight loss plateaued.”

However, efficacy is just one of the factors that doctors consider before prescribing GLP-1 drugs. Others include:

Safety and tolerability of side effects
Other medical conditions and risk factors
Availability
Insurance coverage

“Over the last couple of weeks to months, there [are] more companies that will cover only semaglutide and not tirzepatide,” Imaeda explained. Many of her patients have received notices from their insurance company informing them they will need to switch from Zepbound to Wegovy in the coming months, she said.

Another consideration is prevention of other diseases—GLP-1s in general have been shown to have benefits for conditions such as cardiovascular disease and dementia, but Wegovy and Zepbound have different secondary treatment approvals.

“Wegovy is FDA approved for secondary prevention of cardiovascular disease, and so I would favor this drug for the patients with a history of cardiovascular disease or stroke,” Shah said. “Zepbound is FDA-approved for patients with moderate-to-severe sleep apnea.”

The Bottom Line

Though Zepbound is more effective than Wegovy, both medications are safe and effective, and can be life-changing for patients.

“Patients who have seen results on these medications are often incredibly grateful that they have been given an opportunity to experience a life where they are not held back by their weight,” Shah said. “They feel better, move better, sleep better, have more self-confidence. And from a medical perspective, [they] have better health parameters such as blood pressure, liver function, and glucose control.”

But while you’re on these medications, remember they aren’t a magic bullet—you will still need to adjust your diet and stay active. Also, Shah said one in 20 patients have side effects that make it difficult for them to stay on the drug, so it’s important to work with a doctor who adjusts your dosing safely, takes your risk factors into account, and thoroughly explains side effects.

Edited by Health, where she edits and publishes news articles on trending health and wellness topics. Her work has been featured in The Heights, an independent student newspaper at Boston College, and Minnesota Monthly." tabindex="0" data-inline-tooltip="true"> Julia Landwehr

Julia Landwehr Julia is the associate news editor for Health, where she edits and publishes news articles on trending health and wellness topics. Her work has been featured in The Heights, an independent student newspaper at Boston College, and Minnesota Monthly. learn more Read more: