Tirzepatide With Diet and Exercise Could Boost Weight Loss

Results from the phase 3 SURMOUNT-3 clinical trial assessing the use of tirzepatide (Mounjaro; Lilly) for individuals with obesity or overweight with weight-related comorbidities concluded that the addition of tirzepatide resulted in an additional 21.1% of weight loss after 12 weeks of intensive lifestyle intervention—a total mean weight loss of 26.6% throughout the 84-week study.

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Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) receptor and a glucagon-like peptide-1 (GLP-1) receptor agonist. The treatment is administered once weekly and is intended to activate the body’s receptors for GIP and GLP-1 through its single molecule. The study authors defined GLP and GLP-1 as natural incretin hormones that are “found in areas of the human brain important for appetite regulation.”

Tirzepatide has been reported to cause a decrease in food intake and modulate fat utilization. This led researchers to compare the efficacy and safety of tirzepatide to a placebo for a total of 72 weeks, after a 12-week intensive lifestyle intervention.

The SURMOUNT-3 (NCT04657016) clinical trial program was a multi-center, randomized, double-blind, parallel, placebo-controlled trial. The researchers included 806 individuals from the United States, Puerto Rico, Argentina, and Brazil who had obesity or overweight with weight-related commodities, except for type 2 diabetes.

After a 12-week period, 579 out of the 806 individuals reached at least 5% body weight reduction. The individuals were then randomly assigned in a 1:1 ratio to receive treatment for tirzepatide or the placebo.

The individuals that were randomly assigned to tirzepatide had a starting dose of 2.5 mg, which was increased every 4 weeks by 2.5 until the 15 mg maximum dose was achieved or maximum tolerated dose was identified. Those who reached the 15 mg dose remained on it as maximum tolerated dose, and those that tolerated 10 mg rather than 15 mg prolonged 10 mg as their maximum tolerated dose.

“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,” said the study authors in a press release.

The press release noted that the study met its co-primary endpoints by attaining an additional 21.1% mean weight loss. The additional weight loss was prior to the 12-week period, in which individuals’ achieved 6.9% weight loss from 241.4 pounds at the beginning of the study.

The secondary endpoint was achieved with a total mean weight loss of 26.6% at 84 weeks, compared to 3.8% of weight loss for individuals that received the placebo.

The study authors noted that the most reported adverse events were nausea, diarrhea, constipation, COVID-19, and vomiting. The adverse events were mild to moderate within individuals.

"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 of product development at Lilly, in a press release, "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."

Reference

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. Lilly Investors. News release. October 15, 2023. Accessed October 24, 2023. https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-shows-additional-211-weight-loss-after-12.