Patients Shed 15% of Body Weight With Tirzepatide, Drugmaker Says

The hotly anticipated combination GIP/GLP-1 receptor agonist tirzepatide (Mounjaro) succeeded in yet another weight-loss trial, maker Eli Lilly announced.

Meeting the first co-primary endpoint of the SURMOUNT-2 trial, people with overweight or obesity and type 2 diabetes taking 15 mg of the once-weekly injectable lost up to 15.7% of their body weight, or 34.4 lb on average.

And those taking 10 mg of tirzepatide lost an average of 13.4% of their body weight (29.8 lb) compared with 3.3% (7.0 lb) for those taking placebo.

While only 30.5% of those on placebo lost at least 5% of their body weight, 86.4% and 81.6% of those on the two dosages of tirzepatide, respectively, were able to achieve this -- meeting the trial's other co-primary endpoint.

Calling this weight loss "substantial and highly clinically meaningful," Robert Gabbay, MD, PhD, chief scientific and medical officer for the American Diabetes Association (ADA), said in a statement that "the ADA Standards of Care recommends personalized weight loss goals for those with diabetes and obesity with maximum benefit seen with weight reductions as high as 15%."

"This further supports the role of tirzepatide in the treatment of individuals with type 2 diabetes and obesity," he added.

However, Gabbay also pointed out that the weight loss seen was less than what was seen with tirzepatide in patients without diabetes. The SURMOUNT-1 trial found an average 22.5% loss of body weight -- mean loss of 52 lb -- with the 15-mg dose of the GIP/GLP-1 receptor agonist in people with overweight or obesity, but free of diabetes.

Last May, FDA approved tirzepatide for type 2 diabetes at three dose levels (5 mg, 10 mg, and 15 mg) as an adjunct to diet and exercise. The agency subsequently granted fast track designation for reviewing the drug as treatment for adults with obesity, or overweight with weight-related comorbidities.

Eli Lilly said it was waiting on the SURMOUNT-2 findings to finally complete the FDA submission for a weight-loss indication. "We expect regulatory action as early as late 2023," the company said in a statement.

If approved, the agent is poised to become a direct competitor to the popular weight loss drug semaglutide (Wegovy), which followed a very similar regulatory pathway, having first been approved for type 2 diabetes under the name Ozempic at a lower dose.

Safety was similar to that reported in SURMOUNT-1. The most common adverse events were gastrointestinal-related, as expected with a GLP-1 receptor agonist, including nausea (20.2% for 10 mg, 21.9% for 15 mg), diarrhea (19.9% and 21.5%), vomiting (10.9% and 13.2%), and constipation (8.0% and 9.0%).

Adverse event-related treatment discontinuations occurred in 3.8% of patients taking the 10-mg dose, 7.4% of those taking the 15-mg dose, and 3.8% of the placebo group, while overall discontinuations occurred in 9.3%, 13.8%, and 14.9% of the groups, respectively.

The 938-participant trial was conducted in eight countries, including the U.S.

The full results of SURMOUNT-2 will be presented at the ADA's 83rd Scientific Sessions in June. Results from SURMOUNT-3 and SURMOUNT-4 are expected later this year.

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