Study details and key findings

In the study, 751 patients were randomized 1:1 to receive either Wegovy or Zepbound between April 2023 and November 2024. Patients received the highest tolerated doses of each drug, which was either 10 milligrams or 15 milligrams for Zepbound and 1.7 milligrams or 2.4 milligrams for Wegovy.

All patients either had a body mass index (BMI) of at least 30 or BMI of at least 27 if they had one or more obesity-related complications, such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. None of the patients had type 2 diabetes. At baseline, the average patient age was 45 years, and the mean BMI was 39.4. Of the participants, 65% were women, and 76% were white.

Overall, the researchers found that patients who received Zepbound lost 20.2% of their body weight — an average weight loss of 50.3 pounds — after 72 weeks, while patients who received Wegovy lost 13.7% of their body weight, or an average of 33.1 pounds.

Almost 32% of patients on Zepbound lost at least a quarter of their body weight, compared to 16% of patients on Wegovy. In addition, patients on Zepbound lost 18.4 cm (7.2 in) around their waists compared to 13 cm (5.1 in) for patients on Wegovy.

Although patients on both treatments saw improvements in diastolic blood pressure, glycated hemoglobin, fasting serum glucose, and lipid levels, those on Zepbound had greater improvements in systolic blood pressure.

"The mean differences between tirzepatide [Zepbound] and semaglutide [Wegovy] in the cardiometabolic risk factors may be clinically relevant considering that reductions in systolic blood pressure of 2 to 5 mm Hg have been shown to reduce the risk of cardiovascular events," the researchers wrote.

Patients on both drugs reported similar side effects, including nausea, constipation, diarrhea, and vomiting. However, fewer patients on Zepbound discontinued treatment due to any adverse events compared to those on Wegovy (6.1% vs. 8%, respectively). 

Commentary

Since the study was funded by Eli Lilly, Zepbound's manufacturer, Céline Gounder, editor-at-large for public at KFF Health News, said the findings should be taken "with a grain of salt." However, she also noted that the research "does look legit, and we have seen hints of this in other studies."

According to Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine and leader of the study, Zepbound may have performed better than Wegovy for weight loss since it targets two hormones (GLP-1 and GIP) instead of just one (GLP-1).

"Two drugs together can produce better weight loss," he said. However, Aronne added that both medications are important tools for treating obesity, which currently affects around 40% of U.S. adults.

GLP-1 drugs can impact patients' health outside of weight loss. "We're seeing people's blood pressure come down, their diabetes numbers, their blood sugars improve, their cholesterol numbers improve," Gounder said. "So this is not just the weight loss, it's also health indicators."

Currently, Wegovy has been approved by FDA to reduce the risk of heart attack, stroke, and heart disease in patients who are overweight or obese and have a history of heart problems. Separately, Zepbound has been approved to reduce the risk of obstructive sleep apnea in obese patients. Some studies have also shown that GLP-1 drugs may reduce the risk of liver and kidney symptoms.

According to Angela Fitch, CMO of obesity care company knownwell, it's important to have a range of medications to treat a condition as widespread as obesity. Although a drug might work well for one patient, it is not guaranteed to be the same for others.

"We're going to need to use them all just because we have so many patients who need treatment," Fitch said.

Advisory Board's weight-related resources

To help you address the growing use of weight-management drugs, Advisory Board offers several resources:

This expert insight outlines the five biggest questions about weight-management drugs and their answers. Similarly, this expert insight addresses what headlines get wrong about weight-management drugs and what healthcare leaders should know instead.

Radio Advisory's Rachel Woods has also covered GLP-1 drugs on the podcast, discussing the potential future of these drugs and how they could help — or hurt — health systems' finances. Other useful resources include this expert insight on the five catalysts that will impact the future of obesity care and this research on four key elements of comprehensive obesity care.

Our weight-management and obesity care resource library can also help leaders understand the current care landscape, manage innovations, and prepare for transformations in care.