Tirzepatide achieved up to 15.7% weight loss in adults with obesity or overweight and type 2 diabetes in SURMOUNT-2 study

The study met both co-primary objectives and all key secondary objectives for tirzepatide compared to placebo for both estimands (Efficacy estimand represents efficacy prior to discontinuation of study drug). Those taking tirzepatide lost up to 15.7% (34.4 lb. or 15.6 kg) of body weight for the efficacy estimand. SURMOUNT-2 is the second global phase III clinical trial that evaluated the efficacy and safety of tirzepatide for chronic weight management. The trial evaluated 938 adult participants with obesity or overweight and type 2 diabetes.

"Obesity is a difficult-to-manage disease, and it's even more difficult for people living with type 2 diabetes," said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. "The degree of mean weight reduction seen in SURMOUNT-2 has not been previously achieved in phase 3 trials for obesity or overweight and type 2 diabetes."

For the efficacy estimand, participants taking tirzepatide achieved average weight reductions of 13.4% (29.8 lb. or 13.5 kg) on 10 mg and 15.7% (34.4 lb. or 15.6 kg) on 15 mg compared to placebo (3.3%, 7.0 lb. or 3.2 kg) . Additionally, 81.6% (10 mg) and 86.4% (15 mg) of people taking tirzepatide achieved at least 5% body weight reduction, the other co-primary endpoint, compared to 30.5% of those taking placebo.

Tirzepatide also met all key secondary objectives , which included reduction in A1C and other cardiometabolic parameters. 41.4% (10 mg) and 51.8% (15 mg) of people taking tirzepatide achieved at least 15% body weight reduction compared to 2.6% of those taking placebo. Reduction in A1C compared to placebo was similar to the SURPASS trials in adults with type 2 diabetes. Study participants had a mean baseline body weight of 222 lb. (100.7 kg) and baseline A1C of 8.0%.

For the treatment-regimen estimand, results showed: i. Average body weight reductions: 12.8% (10 mg), 14.7% (15 mg), 3.2% (placebo) ii. Percentage of participants achieving body weight reductions of ?5%: 79.2% (10 mg), 82.7% (15 mg), 32.5% (placebo). iii. Percentage of participants achieving body weight reductions of ?15%: 39.7% (10 mg), 48.0% (15 mg), 2.7% (placebo).

The overall safety profile of tirzepatide was similar to previously reported SURMOUNT and SURPASS trials and to incretin-based therapies approved for the treatment of obesity and overweight. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity, usually occurring during the dose-escalation period. For those treated with tirzepatide (10 mg and 15 mg, respectively), nausea (20.2%, 21.9%), diarrhea (19.9%, 21.5%), vomiting (10.9%, 13.2%) and constipation (8.0%, 9.0%) were more frequently reported compared to placebo (6.3% [nausea], 8.9% [diarrhea], 3.2% [vomiting], 4.1% [constipation]).

Treatment discontinuation rates due to adverse events were 3.8% (10 mg), 7.4% (15 mg) and 3.8% (placebo). The overall treatment discontinuation rates were 9.3% (10 mg), 13.8% (15 mg) and 14.9% (placebo).

Lilly will continue to evaluate the SURMOUNT-2 results, which will be presented at the American Diabetes Association's 83rd Scientific Sessions and submitted to a peer-reviewed journal. Based on these results, Lilly plans to complete the U.S. submission for tirzepatide in adults with obesity or overweight with weight-related comorbidities in the coming weeks. We expect regulatory action as early as late 2023.