Summary: In adults with obesity and prediabetes in the 176-week SURMOUNT-1 analysis, once-weekly tirzepatide produced sustained weight loss of 12.3% to 19.7% versus 1.3% with placebo and reduced diagnosis of type 2 diabetes to 1.3% versus 13.3% (hazard ratio 0.07). The trial was funded by Eli Lilly.
PICO Summary
| Element | Detail |
|---|---|
| Population | Adults with obesity and prediabetes (1032 of the 2539 participants randomised in SURMOUNT-1); phase 3, double-blind, randomised controlled trial, multinational. |
| Intervention | Once-weekly tirzepatide 5 mg, 10 mg or 15 mg for 176 weeks, followed by a 17-week off-treatment period. |
| Comparison | Matching placebo (1:1:1:1 allocation across the three tirzepatide doses and placebo). |
| Outcome | At 176 weeks, mean body-weight change was -12.3% (5 mg), -18.7% (10 mg) and -19.7% (15 mg) versus -1.3% with placebo (P<0.001 for all comparisons). Type 2 diabetes was diagnosed in 1.3% of tirzepatide recipients versus 13.3% on placebo (hazard ratio 0.07; 95% CI 0.0 to 0.1; P<0.001). After 17 weeks off treatment, 2.4% versus 13.7% had type 2 diabetes (hazard ratio 0.12; 95% CI 0.1 to 0.2; P<0.001). Adverse events were mainly mild to moderate gastrointestinal events during dose escalation, with no new safety signals. |
Tirzepatide in obesity with prediabetes (SURMOUNT-1, 3 years)
Phase 3 RCT · obesity and prediabetes · 176 weeks
Over 176 weeks, tirzepatide gave sustained weight loss of 12.3% to 19.7% versus 1.3% with placebo and cut diagnosis of type 2 diabetes to 1.3% versus 13.3% (HR 0.07) in obesity with prediabetes. The endpoint is diabetes diagnosis, not complications.
Expert Commentary
This is the strongest long-term evidence so far for tirzepatide in people with obesity and prediabetes, and my verdict is clearly positive. Weight loss was large and sustained across all three doses, from 12.3% at 5 mg to 19.7% at 15 mg against 1.3% with placebo, and diagnosis of type 2 diabetes fell from 13.3% to 1.3% (hazard ratio 0.07). The difference was still evident 17 weeks after treatment stopped, although diagnoses did rise modestly in the tirzepatide group (2.4% versus 13.7%). The main limitation is the endpoint itself. A diabetes diagnosis is a glycaemic threshold rather than a complication, so it is not yet known whether delaying it prevents microvascular or cardiovascular disease. Can I use this with my patients? Yes, for adults with obesity and prediabetes who meet local licensing and funding criteria, particularly those with further risk factors for progression, provided they understand that treatment is likely to be long term. I would like to see outcome trials that follow this population to complications and report what happens after treatment is withdrawn.
References
Jastreboff AM, le Roux CW, Stefanski A, et al. Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med. 2025;392(10):958-971. doi:10.1056/NEJMoa2410819. PMID: 39536238. ClinicalTrials.gov: NCT04184622.
