Eli Lilly’s tirzepatide (Mounjaro) led overweight people or people with obesity to lose almost a quarter of their weight in a recent trial that lasted over 72 weeks. Average weight loss was about 60lbs. The drug is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist that was approved in 2022 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. This trial excluded people with type 2 diabetes, to see what the drug’s effects were on weight loss independent of diabetes.
The results were presented during The Obesity Society’s 2023 ObesityWeek and published in the journal Nature Medicine.
The phase III SURMOUNT-3 clinical trial evaluated tirzepatide in or overweight adults with weight-related comorbidities, excluding type 2 diabetes, which the drug is already approved for. Tirzepatide met primary endpoints for efficacy and demonstrated superiority to placebo.
“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, 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 trial 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. It randomized adults with obesity or overweight who had at least five percent 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.
The overall safety profile of tirzepatide in SURMOUNT-3 was similar to Lilly’s 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 participants 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.
The SURMOUNT phase III 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.