Tirzepatide cut body weight up to 15.7% in adults with type 2 diabetes, Lilly says

Tirzepatide, the drug Lilly sells as Mounjaro for type 2 diabetes, produced average weight loss of up to 15.7% over 72 weeks in adults who had both type 2 diabetes and obesity or overweight, the company said on April 27, 2023 ^[1]. The results come from SURMOUNT-2, a phase 3 trial that enrolled 938 adults ^[1].

In the trial, participants taking the 10 mg dose lost an average of 13.4% of body weight (29.8 lb, or 13.5 kg), and those taking 15 mg lost 15.7% (34.4 lb, or 15.6 kg), compared with 3.3% (7.0 lb, or 3.2 kg) for placebo ^[1]. Participants started at a mean baseline weight of 222 lb (100.7 kg) ^[1]. About 81.6% of people on 10 mg and 86.4% on 15 mg lost at least 5% of their body weight, one of the trial's two main goals, compared with 30.5% on placebo ^[1]. At least 15% weight loss was reached by 41.4% on 10 mg and 51.8% on 15 mg, compared with 2.6% on placebo ^[1].

Lilly also reported a second set of figures, called a treatment-regimen estimand, that counts everyone assigned to a dose whether or not they kept taking it. Those numbers were lower: average weight loss of 12.8% at 10 mg, 14.7% at 15 mg and 3.2% for placebo ^[1]. By that measure, 79.2% and 82.7% of the tirzepatide groups lost at least 5% of body weight, versus 32.5% on placebo ^[1].

Tirzepatide also met the trial's key secondary goals, which included reductions in A1C and other heart and metabolic measures. Lilly said the A1C reduction was similar to what it saw in earlier trials of the drug in people with type 2 diabetes ^[1]. Participants began with a mean A1C of 8.0% ^[1]. The study ran at sites in the United States, Argentina, Brazil, India, Japan, Puerto Rico, Russia and Taiwan ^[1].

The safety profile was similar to earlier tirzepatide trials and to other incretin-based obesity drugs, Lilly said ^[1]. The most commonly reported side effects were gastrointestinal and generally mild to moderate, usually during the period when the dose was being increased ^[1]. Nausea was reported by 20.2% of people on 10 mg and 21.9% on 15 mg, compared with 6.3% on placebo; diarrhea by 19.9% and 21.5%, versus 8.9%; vomiting by 10.9% and 13.2%, versus 3.2%; and constipation by 8.0% and 9.0%, versus 4.1% ^[1]. Discontinuation because of side effects was 3.8% at 10 mg, 7.4% at 15 mg and 3.8% for placebo ^[1].

Why it matters for patients

Weight loss on incretin drugs has generally been smaller in people with type 2 diabetes than in people without it. In an earlier Lilly trial in people who were obese or overweight but did not have diabetes, the 15 mg dose produced average weight loss of 22.5%, or about 52 lb, Reuters reported ^[2]. The 15.7% result in SURMOUNT-2 is lower. Lilly's Jeff Emmick said the degree of mean weight reduction seen in this trial "has not been previously achieved in phase 3 trials for obesity or overweight and type 2 diabetes" ^[1][2].

Tirzepatide is already approved in the US as Mounjaro, but only to improve blood sugar in adults with type 2 diabetes, not for weight loss ^[1]. A separate approval would be needed before doctors could prescribe it for chronic weight management. The announcement does not establish how tirzepatide compares with other weight-loss options, and the full results have not yet been published in a peer-reviewed journal or presented publicly ^[1]. Details patients often weigh, such as how weight loss differed by age, sex or how long someone had diabetes, were not disclosed in the announcement ^[1].

What happens next

Lilly said it plans to complete its US submission to the FDA for tirzepatide in adults with obesity or overweight with weight-related conditions in the coming weeks, and that it expects regulatory action as early as late 2023 ^[1][2]. The company said the full SURMOUNT-2 results will be presented at the American Diabetes Association's 83rd Scientific Sessions and submitted to a peer-reviewed journal ^[1]. Results from two other trials in the program, SURMOUNT-3 and SURMOUNT-4, are anticipated in 2023 ^[1].