Eli Lilly's Zepbound Shows Superior Weight Loss Over Novo Nordisk's Wegovy In Head-To-Head Trial

Eli Lilly and Company’s LLY Zepbound demonstrated superior weight reduction compared to Novo Nordisk A/S’s NVO Wegovy in a 72-week head-to-head trial.

What Happened: Participants treated with tirzepatide (Zepbound) achieved an average weight loss of 20.2%, compared to 13.7% with semaglutide (Wegovy), representing a 47% greater relative weight reduction, according to detailed results from a direct comparison trial published in The New England Journal of Medicine.

On average, those taking Zepbound lost 50.3 pounds, while those on Wegovy lost 33.1 pounds over the course of the study.

The SURMOUNT-5 Phase 3b open-label clinical trial met its primary endpoint and all five key secondary endpoints, with Zepbound showing superiority across all weight reduction targets. Nearly 65% of Zepbound users achieved at least 15% weight loss compared to 40% on Wegovy, and participants experienced greater waist circumference reduction —7.2 inches versus 5.1 inches.

The safety profile aligned with previous trials, with primarily gastrointestinal-related adverse events that were generally mild to moderate in severity. Discontinuation rates due to adverse events were 6.1% for Zepbound versus 8% for Wegovy.

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Why It Matters: Zepbound’s performance in this direct comparison strengthens Lilly’s position in the rapidly growing weight loss medication market. The drug operates as a dual GIP and GLP-1 receptor agonist, compared to Wegovy, which works solely as a GLP-1 receptor agonist.

The U.S. Food and Drug Administration recently expanded Zepbound’s approval to include treatment for moderate-to-severe obstructive sleep apnea in adults with obesity. Clinical trials showed patients experienced an average of 25 fewer breathing interruptions per hour, with up to 50% no longer exhibiting OSA symptoms after one year.

WW International Inc. WW recently announced a partnership with LillyDirect pharmacy provider Gifthealth to simplify access to Zepbound for eligible self-pay clinic members. According to WeightWatchers, 33% of its clinic patients currently use Zepbound as part of their weight management plan, with prescriptions more than doubling in recent months.

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Disclaimer: This content was partially produced with the help of AI tools and was reviewed and published by Benzinga editors.