SURMOUNT-3: Tirzepatide Induces Further Body Weight Reduction Following Lifestyle Intervention

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Presented at Obesity Week 2023, SURMOUNT-3 provides new insight into the effects of tirzepatide in patients with overweight or obesity.

Close-up image of a bathroom scale depicting body weight. | Credit: iStock

Credit: iStock

Data from the SURMOUNT-3 trial presented at Obesity Week 2023 suggest use of tirzepatide (Mounjaro) was associated with an additional 21.1% mean weight loss after 12 weeks of intensive lifestyle intervention in patients with overweight or obesity.

Results of the trial, which examined use of tirzepatide relative to placebo therapy after 12 weeks of lifestyle intervention, suggests use of tirzepatide was associated with a total mean weight loss of 26.6% from study entry to week 84 of the trial.

"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, PhD, senior vice president, product development, Eli Lilly and Company.2 "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."

Key Highlights

  • Tirzepatide in SURMOUNT-3 trial: 21.1% additional weight loss by end of study after 12 weeks of lifestyle intervention.
  • Total mean weight loss with tirzepatide: 26.6% from study entry to week 84.
  • Safety profile consistent with other trials; common adverse events include nausea, diarrhea, and constipation.

Tirzepatide has been in the spotlight of the medical community since results of the SURPASS program demonstrated the benefits of the dual GIP/GLP-1 receptor agonist in management of type 2 diabetes. Just months after the May 2022 approval for type 2 diabetes, the agent cemented its spot in the spotlight with results of the 72-week SURMOUNT-1, which provided evidence of tirzepatide’s effects on body weight in patients with overweight or obesity.3,4

SURMOUNT-3 was designed as a randomized, double-blind, placebo-controlled trial with the intent of comparing tirzepatide against placebo for 72 weeks following a 12-week intensive lifestyle intervention lead-in period. The trial enrolled 806 adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes.1

Per trial protocol, the intensive lifestyle intervention lead-in period included a low-calorie diet, exercise, and weekly counseling sessions. Following the lead-in period, participants who achieved a body weight reduction of 5.0% or greater to a maximally tolerated dose of 10 mg or 15 mg tirzepatide or placebo once weekly for 72 weeks. A total of 579 participants entered the randomized portion of the trial.1

The trial had coprimary endpoints of percent change from randomization in body weight at the end of the trial and proportion of patients with weight loss of 5% or more from randomization to the end of the trial.1

In the treatment efficacy estimand, results indicated use of tirzepatide was associated with an additional 21.1% mean weight loss following the lead-in period compared to a 3.3% increase in body weight among the placebo group 3.3% with placebo (estimated treatment difference [ETD], −24.5 percentage points; 95% Confidence Interval [CI], −26.1 to −22.8; P < .001). Analysis of the treatment regimen estimated suggested the mean change in body weight at week 72 was −18.4% with tirzepatide and 2.5% with placebo (ETD, −20.8 percentage points; 95% CI, −23.2 to −18.5; P < .001).1

Further analysis of the coprimary endpoint suggested the percentage of participants achieving additional weight reduction of 5% or greater was met in 87.5% of the tirzepatide group compared to 16.5% of the placebo group achieving this threshold (odds ratio, 34.6; 95% CI 19.2 to 62.6; P < .001).1

Investigators noted the safety profile observed in SURMOUNT-3 was consistent with other trials in the SURMOUNT and SURPASS programs. Specifically, the most common adverse events were nausea (Tirzepatide: 39.7% vs Placebo: 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%). Investigators also pointed out adverse events led to discontinuation in 10.5% of the tirzepatide group and 2.1% of the placebo group.1

References:

  1. Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial [published online ahead of print, 2023 Oct 15]. Nat Med. 2023;10.1038/s41591-023-02597-w. doi:10.1038/s41591-023-02597-w
  2. Lilly’s 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. Eli Lilly and Company. October 2023.
  3. Campbell P. Tirzepatide (Mounjaro) wins FDA approval for type 2 diabetes. HCP Live. May 13, 2023. Accessed October 16, 2023. https://www.hcplive.com/view/tirzepatide-wins-fda-approval-for-type-2-diabetes.
  4. Campbell P. Tirzepatide further cements weight loss benefit in surmount-3 and surmount-4 trials. HCP Live. July 27, 2023. Accessed October 16, 2023. https://www.hcplive.com/view/tirzepatide-furthers-cements-weight-loss-benefit-in-surmount-3-and-surmount-4-trials.
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