Patients with overweight and obesity treated with tirzepatide achieved mean weight loss of 15.7%, superior to that seen in patients receiving placebo, according to topline findings from the SURMOUT-2 clinical trial.
Tirzepatide, a dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonist, dosed at 10 mg and 15 mg, was associated with mean body weight reductions of 13.4% and 15.7%, respectively, with more than 80% of tirzepatide users achieving weight loss of ≥5%, as announced by Eli Lilly in a press release on April 27.
SURMOUNT-2, the second global phase 3 clinical trial evaluating the safety and efficacy of tirzepatide for chronic weight management, evaluated 938 adults with overweight or obesity and type 2 diabetes (T2D) for 72 weeks. The study follows the SURMOUNT-1 trial, published in June 2022, in which participants with overweight and obesity but without T2D who were treated with tirzepatide achieved weight loss between 16% and 22.5%, reductions described then as “unprecedented.”
"Obesity is a difficult-to-manage disease, and it's even more difficult for people living with type 2 diabetes," said Jeff Emmick, MD, PhD, senior vice president, product development at Eli Lilly and Company, in the news release. "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."
Based on data reported from the phase 3 SURPASS clinical trial program, tirzepatide was approved by the US Food and Drug Administration in May 2022, as an adjunct to diet and exercise to improve glycemic control in adults with T2D and is marketed as Mounjaro.
SURMOUNT-2 was a multicenter, randomized, double-blind, parallel, placebo-controlled trial, with participants enrolled from 8 countries. Investigators randomized the 938 participants in a 1:1:1 ratio to receive tirzepatide 10 mg, tirzepatide 15 mg, or placebo. The trial’s coprimary endpoints were mean percentage change in body weight from baseline and the percentage of patients achieving a body weight reduction of 5% or more at 72 weeks compared to placebo, said Lilly in the release. Secondary endpoints included reductions in Hgb A1C and other cardiometabolic parameters.
All participants randomized to the 2 active treatment arms began the study at a dose of 2.5 mg tirzepatide once weekly followed by stepwise increases every 4 weeks until the goal doses of 10 mg or 15 mg were reached.
Study participants had a mean baseline body weight of 222 lb and baseline A1C of 8.0%.
SURMOUNT-2 investigators reported mean weight changes among tirzepatide-treated participants of -13.4% for those receiving 10 mg and of -15.7% for those on 15 mg compared to a change of -3.3% in participants receiving placebo.
The majority of participants receiving tirzepatide 10 mg and 15 mg achieved body weight reduction of at least 5% compared with placebo, ie, 81.6%, 86.4%, and 30.5%, respectively.
SURMOUNT-2 also met all its key secondary endpoints, according to Lilly, with 41% of participants in the 10 mg and 51.8% of those in the 15 mg study arms losing at least 15% of their baseline body weight compared to 2.6% of those taking placebo. Reductions in Hgb A1c observed in the study were similar to those reported by Lilly in the SURPASS trial.
Lilly reported that the safety profile of tirzepatide in SURMOUNT-2 was commensurate with what was observed in the SURMOUNT-1 and SURPASS trials. The most common adverse events reported were nausea, diarrhea, and vomiting, characteristics of incretin-based therapies now approved to treat overweight and obesity. the GLP-1 and GIP RA class of medications. Symptoms were generally mild, according to the company, and typically clustered during dose-escalation periods. Overall treatment discontinuation rates were 9.3% (10 mg), 13.8% (15 mg) and 14.9% (placebo).
Full results of SURMOUNT-2 are scheduled to be presented in June at the 2023 American Diabetes Association 83rd Scientific Sessions and will be submitted to a peer-reviewed journal.
The FDA granted tirzepatide review fast track status at Lilly’s initial filing of the new drug application (NDA) in October 2022, according to the release. The company is poised, however, to redeem an FDA-awarded priority review voucher which would shorten the standard review time from 10 to 6 months, according to a separate company announcement. The data from SURMOUNT-2 are expected to complete the NDA and Lilly says it expects an FDA decision on the application before the end of 2023.