Tirzepatide Bests Semaglutide for Weight Loss by 47% in Head-to-Head Trial

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Tirzepatide led to a 47% greater reduction in weight compared with semaglutide in the first head-to-head trial between the antiobesity medications from Lilly and Novo Nordisk, respectively. Specifically, topline findings from the phase 3b SURMOUNT-5 trial revealed an average loss of 50.3 lbs (20.2%) among tirzepatide-treated participants vs 33.1 lbs (13.7%) among semaglutide-treated adults after 72 weeks, according to a news release from Lilly.

Study findings also showed superiority of tirzepatide across 5 secondary endpoints, the key result being body weight loss of at least 25% among 31.6% of participants who received tirzepatide compared with 16.1% of those who received semaglutide who reached the designated mark.

"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, senior vice president of global medical affairs at Lilly Cardiometabolic Health, said in the press release.

Tirzepatide is a dual GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist, administered once-weekly by subcutaneous injection; semaglutide acts solely at the GLP-1 receptor and is also administered once-weekly. Both incretin mimetics reduce hunger, increase satiety, and slow gastric emptying and are approved by the FDA for long-term weight management as an adjunct to lifestyle changes including increased physical activity and a reduced-calorie diet. The tirzepatide dual agonism is thought to be associated with the greater observed impact on body weight.

The multicenter, randomized, open-label SURMOUNT-5 trial evaluated the efficacy and safety of Lilly’s tirzepatide, marketed as Zepbound, and Novo’s semaglutide, marketed as Wegovy, in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular disease, who did not have diabetes. Investigators randomly assigned 751 adults in the US and Puerto Rico to receive maximum tolerated dose of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg).

The safety profile of tirzepatide was similar to that observed in previously reported SURMOUNT program clinical trials. The most commonly reported adverse events in SURMOUNT-5 for both tirzepatide and semaglutide were gastrointestinal-related and were generally mild to moderate in severity.

Lilly will amend these topline findings pending further evaluation. Results will be published in a peer-reviewed journal and presented at a medical meeting next year, the company said.

Source: Lilly’s Zepbound® (tirzepatide) superior to Wegovy® (semaglutide) in head-to-head trial showing an average weight loss of 20.2% vs. 13.7%. News release. Eli Lilly and Company. December 4, 2024. Accessed December 4, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head