Eli Lilly and Company has announced positive topline results from its SURMOUNT-1 study evaluating the efficacy and safety of tirzepatide (Zepbound and Mounjaro) for weight management and delay in progression to type 2 diabetes (T2D) in adults with pre-diabetes and obesity or overweight.1
Most notably, tirzepatide reduced the risk of developing T2D by 94% and contributed to an average weight loss of more than 20% among participants taking the medication.
About SURMOUNT-1
Trial Name: A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1)
Clinicaltrials.gov Identifier: NCT04184622
Sponsor: Eli Lilly and Company
Summary: This is a study of tirzepatide in participants with overweight and obesity. The main purpose is to learn more about how tirzepatide affects body weight. The study has 2 phases: A main phase and an extension phase. The main phase of the study will last 72 weeks. Participants with pre-diabetes will continue in the extension for another 2 years.
“Obesity is a chronic disease that puts nearly 900 million adults worldwide at an increased risk of other complications such as type 2 diabetes,” said Jeff Emmick, MD, PhD, senior vice president of product development at Lilly, in a news release.1 “Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the 3-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes.”
SURMOUNT-1 (NCT04184622) was a multi-center, randomized, double-blind, parallel, placebo-controlled trial comparing 5 mg, 10 mg, and 15 mg of tirzepatide to placebo as an adjunct to a reduced-calorie diet and increased physical activity in adults with pre-diabetes and obesity or overweight with at least 1 of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.
Following an initial 72-week primary analysis, with results published in the New England Journal of Medicine in 2022,2 1032 participants with pre-diabetes remained enrolled in the trial for an additional 104 weeks of treatment. Then, participants were monitored in a 17-week off-treatment period. The impact of tirzepatide on body weight and progression to T2D was compared to placebo for the duration of the 3-year study period.
READ MORE: Head-to-Head Comparison of GLP-1 RAs for Weight Loss Tips Scales in Tirzepatide’s Favor
From baseline to week 176 and across both efficacy and treatment-regimen outcomes—defined as efficacy regardless of adherence to randomized treatment—tirzepatide significantly decreased the risk of T2D progression by 94% and 93% respectively, compared to placebo (P < .0001).
Tirzepatide also contributed to substantial weight loss in participants with pre-diabetes and obesity or overweight: At week 176, those taking tirzepatide achieved average weight reductions of 15.4% (5 mg), 19.9% (10 mg), and 22.9% (15 mg), respectively, compared to 2.1% for placebo.
Treatment-regimen outcomes for weight loss among participants with pre-diabetes and obesity or overweight showed similar results. Adults taking tirzepatide achieved average weight reductions of 12.3% (5 mg), 18.7% (10 mg) and 19.7% (15 mg) compared to 1.3% for placebo.
In the 17-week off-treatment follow-up period, some participants experienced weight regain and an increased risk of developing T2D. However, compared to placebo, the risk of T2D progression remained 88% lower (P < .0001) compared to placebo.
In terms of safety, tirzepatide was well-tolerated throughout the 193-week study and maintained a safety profile similar to that demonstrated previously at 72 weeks and other tirzepatide clinical studies. The most common adverse events were gastrointestinal-related, including diarrhea, nausea, constipation, and vomiting.
As approximately 70% of American adults currently have obesity or overweight, these findings highlight the significant potential of tirzepatide in preventing T2D and promoting sustained weight loss among individuals with pre-diabetes and overweight or obesity.3
A detailed report of study findings will be published in a peer-reviewed journal and presented at ObesityWeek 2024 taking place from November 3 to 6.1
Tirzepatide was approved by the FDA as Mounjaro for adults with T2D to improve glycemic control on May 13, 2022, and as Zepbound for adults with obesity or those who are overweight who also have a weight-related comorbid condition on November 8, 2023.4 Tirzepatide is the only approved glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 treatment for chronic weight management.
READ MORE: Diabetes Resource Center
References
2. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
