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On July 27, 2023, Eli Lilly and Company announced topline results of the SURMOUNT-3 and SURMOUNT-4 trials, with both trials achieving all primary endpoints of interest and full results scheduled to be presented later this year.
Data from SURMOUNT-3 and SURMOUNT-4 clinical trials suggest use of tirzepatide was associated with significant, sustained weight loss, with the potential for a greater magnitude of weight loss when combined with intensive lifestyle intervention, according to an announcement from Eli Lilly and Company.
In SURMOUNT-3, which examined use with a 12-week lifestyle intervention, results suggest the combination was associated with a total mean weight loss of 26.6% at 84 weeks. The SURMOUNT-4 trial, which included an open-label lead-in period followed by a double-blind treatment period, met all primary and key secondary objectives for tirzepatide compared to placebo.1
With topline results announced on July 27, 2023, and full results of SURMOUNT-3 and SURMOUNT-4 scheduled to be presented at ObesityWeek and the European Association for the Study of Diabetes, respectively, the studies provide timely insight into the effects of tirzepatide ahead of a potential decision for a chronic weight management indication from the US Food and Drug Administration, which is expected before the close of 2023.1
"The results of SURMOUNT-3 and -4 showed the highest level of weight loss observed in the SURMOUNT program to date," said Jeff Emmick, MD, PhD, senior vice president of product development with Eli Lilly and Company.1 "Whether taking tirzepatide for 88 weeks in SURMOUNT-4 or taking tirzepatide for 72 weeks following intensive caloric restriction in SURMOUNT-3, participants achieved similar mean weight reduction — about 26%. The findings from SURMOUNT-3 challenge the notion that patients living with obesity or overweight can achieve their weight loss goals with diet and exercise alone. Additionally, the findings from SURMOUNT-4 reinforce that obesity should be regarded like other chronic diseases where chronic therapy may be needed to maintain treatment benefits."
Tirzepatide, a dual GLP-1/GIP receptor agonist, has taken the world of diabetes management by storm since initial announcement of data from the SURPASS program. Since, the SURMOUNT clinical program has continued to stoke the medical community with the agent’s potential in management of overweight or obesity. This latest information from the SURMOUNT clinical program comes just more than a month after W. Timothy Garvey, MD, presented data from the SURMOUNT-2 trial at the 83rd Scientific Sessions of the American Diabetes Association (ADA 2023).2
A randomized, double-blind, placebo-controlled trial, SURMOUNT-3 enrolled patients without type 2 diabetes with obesity or overweight with weight-related comorbidities to assess the safety and efficacy of tirzepatide relative to placebo therapy following participation in an intensive lifestyle program. Per trial protocol, the intensive lifestyle intervention lead-in period included a low-calorie diet, exercise, and weekly counseling sessions. The trial had co-primary endpoints of percent change from randomization in body weight at the end of the trial and proportion of patients with weight loss of 5% or more from randomization to the end of the trial.1
At the end of the 12-week lead-in period, mean weight loss among study participants was 6.9%. At the conclusion of the 72-week double-blind treatment period, efficacy estimand analysis indicated those randomized to tirzepatide lost an additional 21.1% of their body weight from randomization compared to those an additional 3.3% among the placebo group (Placebo-adjusted net change: -24.5%). Further analysis revealed 94.4% of the tirzepatide group achieved a weight loss of 5% or greater body at the end of the trial relative to 10.7% among the placebo group.1
In SURMOUNT-4, patients were randomized to tirzepatide or placebo therapy for 52 weeks after a 36-week open-label tirzepatide lead-in period. The primary endpoint of the trial was the mean percent change in body weight from week 36 to week 88. At the end of the 36-week lead-in period, study participants achieved a mean weight loss of 21.1%.1
Upon analysis of the primary endpoint, results suggested use of tirzepatide was associated with a superior mean percent change in body weight relative to placebo. In contrast, those randomized to placebo experienced a mean weight regain of 14.8% at 88 weeks (Placebo-adjusted net change: -21.4%). In their release, Eli Lilly and Company noted the tirzepatide group achieved a mean body weight loss of 26.0% during the trial.1
For more on tirzepatide, check out this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives with W. Timothy Garvey, MD, following his presentation of SURMOUNT-2 data at ADA 2023.