Tirzepatide for Obesity Treatment and Diabetes Prevention

Ania M Jastreboff; Carel W le Roux; Adam Stefanski; Louis J Aronne; Bruno Halpern; Sean Wharton; John P H Wilding; Leigh Perreault; Shuyu Zhang; Ramakrishna Battula; Mathijs C Bunck; Nadia N Ahmad; Irina Jouravskaya; SURMOUNT-1 Investigators

doi:10.1056/NEJMoa2410819

Tirzepatide for Obesity Treatment and Diabetes Prevention

N Engl J Med. 2024 Nov 13. doi: 10.1056/NEJMoa2410819. Online ahead of print.

Affiliation

¹ From the Section of Endocrinology and Metabolism, Department of Medicine, and Section of Pediatric Endocrinology, Department of Pediatrics, Yale Obesity Research Center (Y-Weight), Yale School of Medicine, New Haven, CT (A.M.J.); Diabetes Complications Research Centre, University College Dublin, Dublin (C.W.R.); Eli Lilly, Indianapolis (A.S., S.Z., R.B., M.C.B., N.N.A., I.J.); Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York (L.J.A.); Hospital 9 de Julho, São Paulo (B.H.); University of Toronto and Wharton Weight Management Clinic - both in Toronto (S.W.); the Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom (J.P.H.W.); and University of Colorado School of Medicine, Aurora (L.P.).

PMID: 39536238
DOI: 10.1056/NEJMoa2410819

Abstract

Background: Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.

Methods: We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods.

Results: At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified.

Conclusions: Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

Associated data

ClinicalTrials.gov/NCT04184622