Three-year SURMOUNT-1 data show 94 percent lower risk of progressing to type 2 diabetes

Eli Lilly and the New England Journal of Medicine published three-year results from SURMOUNT-1 on November 13, 2024, showing that adults with obesity and prediabetes who took tirzepatide (sold as Zepbound for weight management and Mounjaro for type 2 diabetes) were far less likely to develop type 2 diabetes than those on placebo ^[1][2]. Over 176 weeks, 1.3% of participants on tirzepatide received a diabetes diagnosis compared with 13.3% on placebo ^[1].

SURMOUNT-1 enrolled 2,539 adults with obesity, of whom 1,032 also had prediabetes ^[1]. Participants were assigned in equal numbers to weekly tirzepatide at 5 mg, 10 mg or 15 mg, or to placebo ^[1]. The prediabetes group stayed on treatment for a total of 176 weeks — about three years, making this the longest completed tirzepatide study to date — followed by 17 weeks off treatment ^[1][2].

The numbers

At week 176, average weight change from baseline was −12.3% with 5 mg, −18.7% with 10 mg and −19.7% with 15 mg, versus −1.3% with placebo (P<0.001 for each comparison) ^[1]. Those figures come from what researchers call the treatment-regimen estimand, which counts everyone regardless of whether they stopped the drug or started other weight-loss treatments. Under the efficacy estimand, which reflects results while people stayed on assigned treatment, the averages were 15.4%, 19.9% and 22.9% versus 2.1% on placebo ^[2]. Both sets of numbers come from the same trial; they answer slightly different questions, which is why headlines have cited both roughly 20% and roughly 23% weight loss.

For diabetes, the hazard ratio was 0.07 (95% CI, 0.0 to 0.1) under the treatment-regimen estimand and 0.06 under the efficacy estimand — a roughly 94% lower risk of progressing to type 2 diabetes across the pooled doses ^[1][2]. Lilly put the number needed to treat at nine, meaning about nine people would need three years of treatment to prevent one new diabetes diagnosis ^[2]. Put another way, nearly 99% of people on tirzepatide remained diabetes-free at 176 weeks ^[2].

The off-treatment stretch tells a different part of the story. Seventeen weeks after stopping, 2.4% of the tirzepatide group and 13.7% of the placebo group had type 2 diabetes, a hazard ratio of 0.12 ^[1][2]. So the gap narrowed somewhat once the drug was withdrawn, though it remained wide. The published abstract and Lilly's release do not give specific weight-regain figures for that 17-week window, so the size of any rebound is not spelled out in these materials.

A post hoc analysis suggested about half of the delay in diabetes onset was linked to medication-driven weight loss, with the rest potentially due to other effects of tirzepatide ^[2]. The trial also reported sustained improvements in fasting insulin, blood pressure, lipids and health-related quality of life through 176 weeks ^[2].

On safety, the researchers reported no new safety signals ^[1]. Other than COVID-19, the most common adverse events were gastrointestinal — most often nausea, diarrhea and constipation — mostly mild to moderate and concentrated during the dose-escalation period in the first 20 weeks ^[1][2]. The overall profile at 193 weeks matched what was seen at 72 weeks ^[2].

Why it matters for patients

Most weight-loss drug data covers about a year to 18 months. This is one of the first looks at what three continuous years on a GIP/GLP-1 medication does, and it addresses a question many people with prediabetes ask: does the weight loss translate into avoiding diabetes? In this trial, it did, and the weight loss did not fade over the second and third years ^[1][2].

The off-treatment data is equally practical. The rise in diagnoses after 17 weeks without the drug supports the framing that obesity is a chronic condition requiring ongoing treatment, as Lilly's development lead described it ^[2]. That has real consequences for insurance coverage, cost and refill access, since stopping may not lock in the benefit.

Two caveats belong with these results. The trial was funded by Eli Lilly, and several authors are Lilly employees ^[1]. And these findings apply to adults with obesity or overweight who also had prediabetes — not to everyone taking tirzepatide.

What happens next

The paper was published online November 13, 2024, and appeared in the March 6, 2025 print issue ^[1]. Lilly said studies of tirzepatide in chronic kidney disease and in obesity-related illness and death are ongoing, and that it had submitted obstructive sleep apnea data to the FDA and planned to submit heart failure with preserved ejection fraction data ^[2]. Whether regulators will add a diabetes-prevention claim to the label is not addressed in these sources.