The latest findings from phase 3 clinical trials of tirzepatide, sold as Mounjaro, have demonstrated that if taken after an initial weight loss brought about by diet and lifestyle changes, the drug can lead to significant additional weight reduction.
The drug semaglutide, sold as Ozempic and Wegovy, has made news for its ability to shed weight. Its competitor, tirzepatide (Mounjaro), has been undergoing phase 3 clinical testing to evaluate its weight-loss abilities.
This is the third iteration of tirzepatide clinical trials, which began with SURMOUNT-1. The findings of the 72-week SURMOUNT-3 study, sponsored by pharmaceutical company Eli Lilly, provided evidence that tirzepatide led to additional weight loss in people who’d already lost 5% or more of their body weight due to lifestyle interventions before starting the drug.
“We are excited about the results of the SURMOUNT-3 trial,” said Gitanjali Srivastava, one of the study’s co-authors. “This medication has already proven to be highly effective as a treatment for persons with type 2 diabetes. This research provides solid evidence that it is also extremely effective as a tool to achieve significant, life-changing weight loss, in conjunction with a low-calorie diet, exercise and frequent nutrition and behavioral counseling.”
Tirzepatide mimics the actions of two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which work together to stimulate insulin secretion and slow stomach emptying, giving a feeling of fullness for longer.
Before being given the drug or a placebo, 806 participants took part in a 12-week ‘lead-in period’ of intensive lifestyle intervention consisting of a reduced-calorie diet, physical activity of 150 minutes or more per week, and frequent behavioral counseling.
Participants had at least one obesity-related complication, excluding diabetes. The 579 participants who achieved at least a 5% reduction in body weight at the end of the lead-in period were randomized to receive either tirzepatide or a placebo. Five percent was chosen because it’s been shown that decreasing baseline body weight by 5 to 10% reduces the likelihood of developing type 2 diabetes and improves cardiometabolic risk factors, such as blood pressure, and other obesity-related complications.
The starting dose of tirzepatide was 2.5 mg, which was increased by 2.5 mg every four weeks until a maximum tolerated dose of 10 mg or 15 mg per week was achieved. At the beginning of the study, the mean body weight was 241.4 lb (109.5 kg). At the end of the 12-week lead-in, participants had achieved a mean weight loss of 6.9%, or 16.8 lb (7.6 kg).
Participants in the tirzepatide group achieved an additional mean weight loss of 21.1%. From the beginning of the lead-in period to the end of the study – a total of 84 weeks – they achieved a total mean weight loss of 26.6%, or 64.4 lb (29.2 kg). Participants taking the placebo achieved a total mean weight loss of 3.8%, or 9.0 lb (4.1 kg) over the same period of time.
The tirzepatide-induced weight loss produced benefits such as lower blood pressure, better blood lipid levels and blood glucose control compared with the placebo group. The most frequently reported adverse events were gastrointestinal – nausea, diarrhea, and constipation – which were mostly mild to moderate in severity and occurred primarily during dose escalation.
“Tirzepatide, following on the heels of semaglutide 2.4 mg once weekly for adults with overweight or obesity, brings a new era of incretin-based therapies that can achieve beyond just the clinically meaningful 5% weight loss,” Srivastava said. “These novel therapies are changing the landscape of obesity treatment rapidly, and still more are in development. For persons with obesity, there is now hope coupled with scientific evidence.”
While Mounjaro, Ozempic and Wegovy can all lead to weight loss, only Wegovy has been approved by the FDA for chronic weight management. Mounjaro and Ozempic are still only approved for what they were originally designed for, to control blood sugar levels in type 2 diabetics.
The study was published in the journal Nature Medicine.
Source: Vanderbilt University Medical Center