Three years of the dual-action peptide drug tirzepatide reduced body weight by up to 20% and slashed the risk of developing type 2 diabetes by 93% in people with obesity and prediabetes.
93% diabetes risk reductiononly 1.3% of tirzepatide-treated participants with prediabetes developed type 2 diabetes vs 13.3% on placebo over 3 years (HR 0.07)
What the researchers found
Three years of once-weekly tirzepatide in people with obesity and prediabetes produced sustained weight loss of 12-20% (dose-dependent) versus 1.3% with placebo. Most remarkably, tirzepatide reduced progression to type 2 diabetes by 93% (1.3% vs 13.3%, HR 0.07, p<0.001). Even after 17 weeks off treatment, diabetes protection persisted (2.4% vs 13.7%, HR 0.12). The most common side effects were GI symptoms, mostly mild-moderate during dose escalation, with no new safety signals over 3 years.
Why it matters
This is the first major trial to demonstrate that a peptide drug can prevent type 2 diabetes while simultaneously treating obesity over 3 years. A 93% reduction in diabetes onset is among the largest preventive effects ever demonstrated for any medication, potentially reframing obesity treatment as diabetes prevention.
The numbers in context
n=1,032 with obesity+prediabetes · 176 weeks treatment · weight loss: -12.3% (5mg), -18.7% (10mg), -19.7% (15mg) vs -1.3% placebo · diabetes onset: 1.3% vs 13.3% (HR 0.07) · 93% diabetes risk reduction · p<0.001 for all
How the study worked
Phase 3, double-blind, randomized, placebo-controlled trial (SURMOUNT-1). 2,539 total participants randomized 1:1:1:1 to tirzepatide 5mg, 10mg, or 15mg weekly or placebo. This analysis focused on the 1,032 participants with obesity and prediabetes, treated for 176 weeks (3.4 years) followed by a 17-week off-treatment period. Key endpoints: percent weight change at 176 weeks and type 2 diabetes onset during treatment and off-treatment periods.
Who was studied
1,032 adults with obesity and prediabetes (from 2,539 total SURMOUNT-1 participants)
What this study cannot tell us
Industry-funded (Eli Lilly). The analysis focused on the prediabetes subgroup (1,032 of 2,539 total participants). Weight regain and diabetes onset after long-term drug discontinuation beyond 17 weeks remain unknown. Cost and access barriers may limit real-world impact. GI side effects during dose escalation may affect tolerability.
How to read the evidence
This is the highest level of clinical evidence: a large Phase 3, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine, with 1,032 participants followed for 3 years. The trial was pre-registered, endpoints were controlled for type I error, and results were highly statistically significant.
When this study was published
Published in 2025, this represents the 3-year extension of the SURMOUNT-1 trial that originally reported 72-week results. It provides the longest-duration data on tirzepatide for obesity and is one of the most consequential peptide drug studies of the decade.
The bigger picture
This study marks a paradigm shift in how we think about obesity and diabetes. Tirzepatide is the first peptide drug to demonstrate both substantial long-term weight loss and near-complete prevention of diabetes progression in a single treatment. Combined with the success of semaglutide in the STEP and SELECT trials, these results cement incretin-based peptide therapies as potentially the most transformative class of drugs in a generation — treating obesity as a disease rather than a lifestyle issue and preventing its most devastating consequences.
Questions still open
- Will diabetes risk rebound over longer periods after tirzepatide discontinuation, or is the 3-year benefit durable?
- How does tirzepatide's diabetes prevention compare to intensive lifestyle intervention programs like the Diabetes Prevention Program?
- Could tirzepatide be cost-effectively used as a preventive medication in the millions of people with prediabetes worldwide?
Common questions
What is tirzepatide and how is it different from semaglutide?
Does this mean tirzepatide can prevent diabetes permanently?
Read the original research
Tirzepatide for Obesity Treatment and Diabetes Prevention.
The New England journal of medicine, 392(10), 958-971
Citation
Jastreboff, Ania M; le Roux, Carel W; Stefanski, Adam; Aronne, Louis J; Halpern, Bruno; Wharton, Sean; Wilding, John P H; Perreault, Leigh; Zhang, Shuyu; Battula, Ramakrishna; Bunck, Mathijs C; Ahmad, Nadia N; Jouravskaya, Irina. (2025). Tirzepatide for Obesity Treatment and Diabetes Prevention.. The New England journal of medicine, 392(10), 958-971. https://doi.org/10.1056/NEJMoa2410819