Zepbound bests Wegovy in head-to-head weight-loss trial
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Key takeaways:
- Zepbound conferred more weight loss than Wegovy at 72 weeks in patients with overweight or obesity.
- About twice as many patients taking Zepbound lost at least 25% of body weight vs. those taking Wegovy.
Eli Lilly announced top-line results of the SURMOUNT-5 trial in which patients with overweight or obesity assigned tirzepatide lost more weight than those assigned semaglutide.
SURMOUNT-5 was a phase 3b clinical trial comparing the GLP-1/GIP receptor agonist tirzepatide (Zepbound, Eli Lilly) with the GLP-1 receptor agonist semaglutide 2.4 mg (Wegovy, Novo Nordisk) for weight loss in patients with overweight or obesity without diabetes but with at least one weight-related comorbidity, according to a press release issued by Eli Lilly. Both drugs are approved by the FDA for treatment of obesity.
At 72 weeks, the primary endpoint of average weight loss was 20.2% in the tirzepatide group compared with 13.7% in the semaglutide group, for a relative difference of 47%, Eli Lilly stated in the release.
The key secondary endpoint of body weight loss of at least 25% was achieved in 31.6% of the tirzepatide group compared with 16.1% of the semaglutide group, according to the release.
The safety profile of tirzepatide was similar to that observed in other studies from the SURMOUNT trial program, and the most common adverse events in both groups were gastrointestinal, generally mild to moderate in severity, Eli Lilly stated in the release.
“Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice,” Leonard C. Glass, MD, FACE, senior vice president of global medical affairs at Lilly Cardiometabolic Health, said in the release. “We are thrilled that today’s findings showed the superior weight loss of Zepbound, which helped patients achieve 47% more relative weight loss compared to Wegovy. Zepbound is in a class of its own as the only FDA-approved dual GIP and GLP-1 receptor agonist obesity medication, and it’s changing how millions of people manage this chronic disease.”
The results will be presented at a medical conference and published in a peer-reviewed journal in 2025, according to the release.
Perspective
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I’m not surprised by these results since dual incretin agonists like tirzepatide offer a stronger, more comprehensive effect on weight loss than GLP-1 agonists like semaglutide because they target both GLP-1 and GIP receptors, providing synergistic benefits in appetite suppression, fat metabolism and insulin sensitivity. GLP-1 decreases appetite and increases satiety (feeling of fullness), while GIP may enhance fat oxidation and improve insulin sensitivity.
This combination leads to a more comprehensive effect on both food intake and fat metabolism, which may contribute to greater overall weight loss than semaglutide, which only targets GLP-1. This combined approach results in greater overall weight loss and would be expected to offer more pronounced benefit for patients with adiposity-related chronic disease like metabolic dysfunction-associated steatotic liver disease, type 2 diabetes, obstructive sleep apnea, polycystic ovary syndrome, etc. The side-effect profile and tolerability is similar to that of semaglutide.
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