Zepbound Beats Wegovy for Weight Loss in Obesity, Head-to-Head Study Shows

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A head-to-head study of tirzepatide (Zepbound) and semaglutide 2.4 mg (Wegovy) indicates tirzepatide offered greater weight loss benefits, with nearly 50% of patients using tirzepatide losing 20% or more of their body weight.

Results of the study point to differences between tirzepatide and semaglutide for total weight loss and changes in waist size achieved.

“Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before,” said the trial’s lead researcher, Louis J. Aronne, M.D., director of the Comprehensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, in a news release.

In recent years, more people have been paying attention to obesity and new medications that help with weight loss. This trend has led to semaglutide, which is marketed as Ozempic for its Type 2 diabetes indications, becoming the second highest grossing drug in 2024, with reports indicating sales topped $16.9 billion — a 26% jump from 2023.

However, tirzepatide, a combination therapy targeting a pair of hormones involved in hunger and blood sugar regulation, has also gained significant attention. To test how well tirzepatide works, Eli Lilly and Company created the SURMOUNT research program. This includes several clinical trials for people with obesity or Type 2 diabetes.

About the SURMOUNT-5 Study

The SURMOUNT-5 trial, launched in 2023, was designed to compare tirzepatide and semaglutide directly. It took place at 32 sites in the U.S. and Puerto Rico.

To join the study, patients had to:

• Be age 18 or older
• Have a body mass index, or BMI, of 30 or more, or 27 or more with an obesity-related condition
• Have tried and failed at least one diet to lose weight

A total of 751 people took part. They were randomly placed into two groups: One received tirzepatide and the other received semaglutide.

Who Was in the Study?

The average patient was 45 years old. About 65% were women, and about 76% were White. The average weight was 249 pounds, and the average BMI was 39. Half had at least two obesity-related conditions, such as high blood pressure or sleep apnea. On average, participants had lived with obesity for 16 years.

What Did the Study Measure?

The main goal was to see how much weight people lost after 72 weeks. Researchers also looked at how many people lost at least 10%, 15%, 20% or more of their body weight, and whether waist size went down.

Results: Tirzepatide Helped More People Lose More Weight

Here’s what the study found:

Average percent of body weight lost:

• Tirzepatide: 20.2%
• Semaglutide: 13.7%
• Tirzepatide led to 6.5% more weight loss.

Average pounds lost:

• Tirzepatide: about 50 pounds
• Semaglutide: about 33 pounds
• Tirzepatide helped people lose about 17 pounds more.

Percent of people reaching key weight-loss goals:

• 10% or more: 82% (tirzepatide) vs. 61% (semaglutide)
• 15% or more: 65% vs. 40%
• 20% or more: 48% vs. 27%
• 25% or more: 32% vs. 16%
• 30% or more: 20% vs. 7%

Side Effects and Safety

Both drugs had similar side effects. The most common were stomach-related issues like nausea or diarrhea. Serious side effects were rare. Fewer than 5% of patients in either group stopped treatment because of side effects.