SURMOUNT-5: Tirzepatide Bests Semaglutide in Head-to-Head Weight Loss Trial

Tirzepatide (Zepbound) bests semaglutide 2.4 mg (Wegovy) for weight loss, according to a head-to-head trial.

Named the SURMOUNT-5 trial, results, which Eli Lilly and Company announced on December 04, 2024, indicate tirzepatide contributed to a mean body weight reduction of 20.2% vs 13.7% achieved with semaglutide. The release highlights this is a 47% greater relative weight loss at 72 weeks, with tirzepatide also besting semaglutide on 5 key secondary endpoints.

"Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice," said Leonard C. Glass, MD, FACE, senior vice president of global medical affairs at Lilly Cardiometabolic Health.

In the last 5 years, few phenomena have gripped the medical community and public consciousness in the same fashion as the rise of incretin therapies. Led by semaglutide, the explosion in interest in incretin therapies coincided with a need for interventions to address the growing burden of metabolic illness in the US. However, for many, the potential of semaglutide represented a steppingstone to the future, with dual incretin therapies, namely tirzepatide, gaining momentum in clinical trial programs.

Beginning with data from the SURPASS program, which was used to support the approval of tirzepatide as the first FDA-approved GIP and GLP-1 receptor agonist in type 2 diabetes. Subsequent trials, including those from the SURMOUNT program, began to offer additional evidence of the effects of tirzepatide.

A multicenter, randomized, open-label, phase 3b trial, SURMOUNT-5 was launched to compare the efficacy and safety of tirzepatide compared with semaglutide in adults with obesity or overweight without diabetes and at least 1 of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. A total of 751 patients from sites in the US and Puerto Rico were randomized in a 1:1 ratio to receive maximum tolerated dose of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg).

The primary outcome of interest for the trial was percent change from baseline in body weight at 72 weeks. Primary analysis of the trial demonstrated use of tirzepatide was associated with a weight loss of 20.2% compared to 13.7% with semaglutide. According to Eli Lilly and Company, those receiving tirzepatide had a mean weight loss of 50.3 lbs compared to 33.1 lbs with semaglutide.

Among the 5 key secondary endpoints, the release from Eli Lilly and Company noted 31.6% of people taking tirzepatide achieved a body weight reduction of least 25% compared to just 16.1% of those taking semaglutide.

"We are thrilled that today's findings showed the superior weight loss of [tirzepatide], which helped patients achieve 47% more relative weight loss compared to [semaglutide]. [Tirzepatide] 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,” Glass added.

References:

1. Eli Lilly and Company. Lilly’s Zepbound® (tirzepatide) superior to Wegovy® (SEMAGLUTIDE) in head-to-head trial showing an average weight loss of 20.2% vs. 13.7%. 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.
2. Campbell P. Surmount-1: Tirzepatide provides significant, sustained weight loss in obesity. HCP Live. June 4, 2022. Accessed December 4, 2024. https://www.hcplive.com/view/surmount-1-tirzepatide-provides-significant-sustained-weight-loss-in-obesity.