Tirzepatide Bests Semaglutide in Relative, Average Weight Loss in Obesity, Overweight

Topline results from the SURMOUNT-5 clinical trial announced today show that tirzepatide (Zepbound) use was associated with a 47% greater relative weight loss vs semaglutide (Wegovy), according to a news release from tirzepatide manufacturer Eli Lilly.¹

Additionally, results showed that by week 72, tirzepatide beat out semaglutide on the primary endpoint—percent change in bodyweight from baseline—and all key secondary endpoints.

Participants in the phase 3b, open-label, randomized SURMOUNT-5 clinical trial (NCT05822830) experience average weight loss of 20.2% with tirzepatide, vs 13.7% with semaglutide.

“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. “We are thrilled that todays findings showed the superior weight loss of [tirzepatide].” Tirzepatide is the only FDA-approved dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist medication to treat obesity.

A cohort of 751 adult patients with obesity or overweight without diabetes and with at least 1 comorbidity including hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease were randomly assigned 1:1 to receive either a 10 mg or 15 mg tirzepatide or 1.7 mg or 2.4 mg semaglutide. The primary goal of the study was demonstrating the superiority of tirzepatide via percent change in baseline body weight at 72 weeks.

READ MORE: Q&A: Understanding the Role of Tirzepatide, Semaglutide in Cardiovascular Disease

Among key secondary endpoints, investigators found that 31.6% of participants in the tirzepatide group achieved at least 25% body weight loss compared with 16.1% in the semaglutide group. These results echo those seen in a real-world study comparing the 2 medications in a cohort of 41,222 patients, published in JAMA Internal Medicine earlier this year.²

Data from the SURMOUNT-1 (NCT04184622) clinical trial, shared earlier this year,³ were also positive: The study, which evaluated the efficacy and safety of tirzepatide for weight management and delay in progression to type 2 diabetes in adults with prediabetes and obesity or overweight found that tirzepatide reduced the risk of developing T2D by 94% and contributed to an average weight loss of more than 20% among participants.

Tirzepatide was first approved by the FDA as Mounjaro for adults with type 2 diabetes in May 2022⁴; approval for adults with obesity or excess weight and weight-related medical problems, as Zepbound, was granted in November 2023.⁵

Approximately 70% of US adults have overweight or obesity, and many of these adults are living with a weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia. Losing just 5% to 10% of body weight is associated with a reduced risk of cardiovascular disease in this patient population.

Initial approval of tirzepatide was granted based on data from two phase 3 randomized, double-blind, placebo-controlled clinical trials, SURMOUNT-1 and SURMOUNT-2 (NCT04657003). The SURMOUNT phase 3 global clinical development program began in late 2019. Studies of tirzepatide in chronic kidney disease and in morbidity and mortality in obesity are ongoing; the company submitted data for the drug’s use in moderate to severe obstructive sleep apnea and obesity, and heart failure with preserved ejection fraction and obesity, to the FDA earlier in 2024.

Data from SURMOUNT-5 will be published in a peer-reviewed medical journal and presented at a medical meeting in 2025.

READ MORE: Obesity Resource Center

References

1. 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. December 4, 2024. Accessed December 4, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head

2. Biscaldi L. Head to head comparison of GLP-1 RAs for weight loss tips scales in tirzepatide’s favor. Drug Topics. July 9, 2024. Accessed December 4, 2024. https://www.drugtopics.com/view/head-to-head-comparison-of-glp-1-ras-for-weight-loss-tips-scales-in-tirzepatide-s-favor

3. Massaro L. Tirzepatide demonstrates 94% diabetes reduction, 22% weight loss in SURMOUNT-1 study. Drug Topics. August 21, 2024. Accessed December 4, 2024. https://www.drugtopics.com/view/tirzepatide-demonstrates-94-diabetes-reduction-20-weight-loss-in-surmount-1-study

4. Wheeler K. Novel, dual-targeted treatment for T2D is FDA approved. Drug Topics. July 12, 2022. Accessed December 4, 2024. https://www.drugtopics.com/view/novel-dual-targeted-treatment-for-t2d-is-fda-approved

5. Biscaldi L. Breaking: FDA approves tirzepatide injection for chronic weight management in obesity, overweight. Drug Topics. November 8, 2024. Accessed December 4, 2024. https://www.drugtopics.com/view/breaking-fda-approves-tirzepatide-injection-for-chronic-weight-management-in-obesity-overweight