Three years of tirzepatide cut type 2 diabetes risk in people with obesity and prediabetes

In a three-year follow-up of the SURMOUNT-1 trial, 1.3% of adults with obesity and prediabetes who took tirzepatide were diagnosed with type 2 diabetes, compared with 13.3% of those who took a placebo, researchers reported in the New England Journal of Medicine ^[1]. The hazard ratio was 0.07, which corresponds to about a 93% lower risk of progressing to diabetes during the treatment period ^[1].

What the trial measured

SURMOUNT-1 enrolled 2,539 people with obesity. Of those, 1,032 also had prediabetes, and this analysis focused on that group. Participants were assigned in a 1:1:1:1 ratio to receive weekly tirzepatide at 5 mg, 10 mg or 15 mg, or a placebo ^[1].

The diabetes analysis covered 176 weeks of treatment, followed by 17 weeks with no treatment. During the 176 weeks, fewer participants in the tirzepatide groups were diagnosed with type 2 diabetes: 1.3% versus 13.3% on placebo (95% confidence interval, 0.0 to 0.1; P<0.001) ^[1].

After the 17 weeks off treatment, 2.4% of participants who had taken tirzepatide and 13.7% of those who had taken placebo had type 2 diabetes (hazard ratio, 0.12; 95% confidence interval, 0.1 to 0.2; P<0.001) ^[1]. In other words, the tirzepatide group's advantage was smaller once the drug was stopped, and a few more diagnoses appeared in both groups.

Weight and side effects

At 176 weeks, average body weight changed by -12.3% with the 5 mg dose, -18.7% with 10 mg and -19.7% with 15 mg, compared with -1.3% on placebo (P<0.001 for all comparisons) ^[1].

Aside from COVID-19, the most common adverse events were gastrointestinal. Most were mild to moderate and occurred mainly during dose escalation in the first 20 weeks of the trial. The researchers reported no new safety signals ^[1].

Why it matters for patients

Prediabetes is a common step on the path to type 2 diabetes, and the trial was designed to test whether treating obesity with tirzepatide changes that trajectory. Three years of data is longer than any other randomized tirzepatide follow-up published so far ^[1], so it gives a clearer picture of what happens with sustained treatment than the 72-week results reported earlier from the same trial ^[1].

The results apply to a specific group: adults with obesity who also had prediabetes. The study did not test tirzepatide as a diabetes prevention drug in people without obesity, and it did not compare tirzepatide with other GLP-1 or dual-agonist medications ^[1].

The analysis does not separate how much of the lower diabetes risk came from weight loss itself and how much came from other effects of the drug ^[1]. It also does not address whether the drug's label would be changed to include diabetes prevention, or how insurers might cover it for that purpose; those questions are not answered in the publication ^[1].

Gastrointestinal side effects were the most common complaint and were concentrated in the first months of treatment ^[1], which is consistent with how this drug class is generally described in the trial's earlier reports.

What is not yet known

What happens after three years of treatment has not been reported. The trial included a 17-week off-treatment period, but longer gaps, weight change after stopping, and diabetes diagnoses beyond that window are not described ^[1].

Whether the reduction in diabetes diagnoses persists for years after people stop taking tirzepatide is also not established ^[1]. The journal later published letters discussing the trial, along with a reply from the authors, in June 2025 ^[1].

The trial was funded by Eli Lilly and registered as NCT04184622 ^[1]. Tirzepatide is the active ingredient in Mounjaro, which is approved for type 2 diabetes, and in Zepbound, which is approved for obesity.