Tirzepatide shows additional 21.1% weight loss after 12 weeks of intensive lifestyle intervention, for a total mean weight loss of 26.6% from study entry over 84 weeks

Tirzepatide met both co-primary endpoints for the efficacy estimandi and treatment-regimen estimand, demonstrating superiority to placebo during the 72-week double-blind treatment period.

SURMOUNT-3 evaluated the efficacy and safety of tirzepatide compared to placebo for 72 weeks after a 12-week intensive lifestyle intervention lead-in period that included a low-calorie diet, exercise and frequent counseling sessions. The trial randomized adults with obesity or overweight who had at least 5% body weight reduction by the end of the 12-week lead-in period to placebo or tirzepatide. At study entry, the mean body weight was 241.4 lb. (109.5 kg). At the end of the 12-week lead-in period, participants achieved 6.9% (7.6 kg or 16.8 lb.) mean weight loss. In a co-primary endpoint, following the lead-in period, participants taking tirzepatide achieved an additional 21.1% mean weight loss. In a secondary endpoint, participants achieved a total mean weight loss of 26.6% (29.2 kg or 64.4 lb.) from study entry over 84 weeks. Participants on placebo achieved a total mean weight loss of 3.8% (4.1 kg or 9.0 lb.) from study entry over 84 weeks.

"In this study, people who added tirzepatide to diet and exercise saw greater, longer-lasting weight reduction than those taking placebo," said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. "While intensive lifestyle intervention is an important part of obesity management, these results underscore the difficulty some people face maintaining weight loss with diet and exercise alone."

The overall safety profile of tirzepatide in SURMOUNT-3 was similar to previously reported SURMOUNT and SURPASS trials . The most commonly reported adverse events in SURMOUNT-3 were gastrointestinal-related and generally mild to moderate in severity. The most frequent events reported by those on tirzepatide compared with placebo, respectively, were nausea (39.7% vs. 14.0%), diarrhea (31.0% vs. 9.2%), constipation (23.0% vs. 6.8%), COVID-19 (23.0% vs. 25.3%) and vomiting (18.1% vs. 1.4%). Adverse events led to discontinuation of study treatment in 10.5% of participants taking tirzepatide and 2.1% taking placebo.

About SURMOUNT-3 and the SURMOUNT clinical trial program: SURMOUNT-3 (NCT04657016) was a multi-center, randomized, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide to placebo for 72 weeks after a 12-week intensive lifestyle intervention lead-in period in adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes. The trial enrolled 806 participants across the U.S., including Puerto Rico, Argentina and Brazil to a lead-in period with intensive lifestyle intervention. After 12 weeks, 579 participants achieved at least 5% body weight reduction and were randomized in a 1:1 ratio to receive tirzepatide or placebo. The co-primary objectives of the study were to demonstrate that tirzepatide is superior in percent change in body weight from randomization and percentage of participants achieving ?5% body weight reduction from randomization at 72 weeks compared to placebo.

SURMOUNT-3 utilized a maximum tolerated dose of 10 mg or 15 mg once-weekly. The starting dose of 2.5 mg tirzepatide was increased by 2.5 mg every four weeks until maximum tolerated dose was achieved. Participants who tolerated 15 mg continued on 15 mg as their maximum tolerated dose. Participants who tolerated 10 mg but did not tolerate 15 mg continued on 10 mg as their maximum tolerated dose.

The SURMOUNT phase 3 global clinical development program for tirzepatide in chronic weight management began in late 2019 and has enrolled more than 5,000 people with obesity or overweight across six registration studies, four of which are global studies. The primary period of SURMOUNT-1 was completed in 2022 and SURMOUNT-2 was completed in the first half of 2023. Topline data for SURMOUNT-3 and SURMOUNT-4 were announced on July 27, 2023; full results for SURMOUNT-4 were presented this month at the European Association for the Study of Diabetes Annual Meeting (EASD 2023).

Note; The efficacy estimand represents efficacy prior to discontinuation of study drug. The treatment-regimen estimand represents the estimated average treatment effect regardless of treatment discontinuation.

See-15 October 2023:"Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase III trial"-Thomas A. Wadden, Ariana M. Chao, Sriram Machineni, Robert Kushner, Jamy Ard, Gitanjali Srivastava, Bruno Halpern, Shuyu Zhang, Jiaxun Chen, Mathijs C. Bunck, Nadia N. Ahmad & Tammy Forrester. Nature Medicine (2023).-DOI https://doi.org/10.1038/s41591-023-02597-w.