Mean Weight Loss with Tirzepatide Reaches 26% Across 2 Pivotal Phase 3 Clinical Trials

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Use of tirzepatide in the pivotal phase 3 SURMOUNT-3 and SURMOUNT-4 clinical trials was associated with mean weight loss of 26.6% among participants with obesity or overweight with associated comorbidities excluding type 2 diabetes (T2D), according to an announcement from Eli Lilly on July 27.

Combined, the latest findings in the company’s clinical trial program evaluating the novel dual incretin mimetic for weight management “showed the highest level of weight loss observed in the SURMOUNT program to date," the company stated.

The US Food and Drug Administration (FDA) approved tirzepatide (marketed as Mounjaro), a once-weekly glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist, on May 13, 2022, as an adjunct to diet and exercise for improving glycemic control in adults with T2D. The agent’s potential to support weight loss has been successfully demonstrated in the SURMOUNT-1 trial in individuals with obesity or overweight plus related complications but without T2D and the SURMOUNT-2 trial, also in patients with obesity and overweight plus complications but without T2D, the company noted.

SURMOUNT-3

SURMOUNT-3 evaluated the safety and efficacy of tirzepatide compared to placebo for 72 weeks following a 12-week period of intensive lifestyle modification, including a reduced-calorie diet, physical activity, and weekly behavioral counseling. Investigators randomly assigned the 579 participants who had at least a 5% reduction in body weight at the 12-week mark to once-weekly subcutaneous tirzepatide or placebo. Average baseline weight among participants was 241.4 lbs, according to Lilly, and mean weight loss after the intensive lifestyle intervention was 6.9%.

SURMOUNT-3 participants assigned to receive terzepatide shed an additional 21.1% of their body weight over the 72-week double-blind treatment period, a coprimary study endpoint, compared to a mean weight regain of 3.3% among placebo-treated participants. Lilly reported a placebo-adjusted net weight change of -24.5%. Further, and satisfying criteria for the second coprimary endpoint, nearly all (94.4%) of those taking tirzepatide attained an additional reduction in body weight of ≥5% during the 72 weeks compared to 10.7% of those in the placebo group. From baseline study entry over 84 weeks, participants taking tirzepatide achieved a total mean weight reduction of 26.6%, according to the company statement.

SURMOUNT-4

In SURMOUNT-4, 783 participants received weekly subcutaneous tirzepatide for a 36-week open label lead-in period after which 670 of them were randomly assigned to continue tirzepatide or be switched to a placebo for the 52-week, double blind treatment period. According to Lilly, mean baseline body weight was 236.6 lbs and mean weight loss at the end of the 36-week lead-in was 21.1%.

Treatment with tirzepatide met the SURMOUNT-4 primary endpoint, superior mean percent change in body weight from week 36 to week 88 vs placebo, an outcome “indicating sustained weight loss,” according to Lilly. Specifically, participants taking tirzepatide lost an additional 6.7% body weight from randomization at 36 weeks in stark contrast to those who were assigned to placebo who regained an average 14.8% between weeks 36 and 88. Investigators calculated the placebo-adjusted net change in weight at -24.1%, the company reported, while the mean body weight loss from study entry over the full 88 weeks was 26.0% for those who were randomized to continue on tirzepatide.

“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,” said Jeff Emmick, MD, PhD, Lilly senior vice president of product development, in the Lilly announcement. “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."

According to the company, full results of the SURMOUNT-3 study will be presented at the ObesityWeek conference in October and results of SURMOUNT-4 at the European Association for the Study of Diabetes Annual Meeting, also in October. Both studies will be submitted for publication in a peer-reviewed journal.

Source: Tirzepatide demonstrated significant and superior weight loss compared to placebo in two pivotal studies. Eli Lilly and Company. July 27, 2023. Accessed July 28, 2023. https://investor.lilly.com/news-releases/news-release-details/tirzepatide-demonstrated-significant-and-superior-weight-loss