Three years of tirzepatide in adults with prediabetes: SURMOUNT-1

Why this study matters

Most weight-management trials last about a year and a half. This analysis followed part of the SURMOUNT-1 group for three years on treatment, plus 17 weeks after stopping. It focused on people with prediabetes, meaning blood sugar that is higher than normal but not yet in the diabetes range. Prediabetes is common in Canada, and one of the main reasons people want to lose weight is to avoid developing type 2 diabetes. This is the longest randomized evidence on tirzepatide (Zepbound, Mounjaro) that we found.

Who was in the study

SURMOUNT-1 randomized 2539 adults living with obesity. Of these, 1032 also had prediabetes at the start, and they are the subject of this report. People with diabetes were excluded from the original trial. Participants in this analysis received their assigned treatment for 176 weeks, then were followed for a 17-week off-treatment period, for 193 weeks in total.

What the researchers did

This was a phase 3, double-blind, randomized, placebo-controlled trial. Randomized means people were assigned by chance. Double-blind means neither participants nor researchers knew who received which treatment. A placebo is an injection that looks the same but contains no medicine. People were split into four equal groups: weekly tirzepatide at 5 mg, 10 mg or 15 mg, or placebo.

This paper reports three key secondary endpoints that were controlled for type I error, which means the trial had a formal statistical plan to avoid false positives on these outcomes. They were the percentage change in body weight to week 176, and the onset of type 2 diabetes over the 176-week and 193-week periods.

What they found

At week 176, average weight change was -12.3% with tirzepatide 5 mg, -18.7% with 10 mg and -19.7% with 15 mg, compared with -1.3% with placebo (R32-C47). The published summary we reviewed does not report confidence intervals for these weight changes.

Fewer people on tirzepatide were diagnosed with type 2 diabetes during the 176 weeks of treatment: 1.3% compared with 13.3% on placebo (R32-C48). The hazard ratio was 0.07, with a 95% confidence interval of 0.0 to 0.1. A hazard ratio compares how quickly an event happens in one group versus another, and a value well below 1 means it happened much less often on tirzepatide. A confidence interval is the range within which the true result most likely sits. As printed in the abstract, this interval is heavily rounded.

After 17 weeks off treatment, 2.4% of the tirzepatide group and 13.7% of the placebo group had type 2 diabetes (hazard ratio 0.12, 95% CI 0.1 to 0.2). The published summary we reviewed does not report how much weight was regained during the 17 weeks off treatment.

Side effects and people who stopped

Apart from COVID-19, the most common side effects were stomach and bowel symptoms. Most were mild to moderate and happened mainly during the first 20 weeks while the dose was being raised. The authors report no new safety signals over three years. The published summary we reviewed does not report the number of people who stopped treatment, or who stopped because of side effects, in each group.

What this study does not tell you

• It covers only the 1032 people with prediabetes. The results do not describe everyone with obesity, and they should not be merged with the main SURMOUNT-1 result.
• The hazard ratio confidence intervals are reported in a heavily rounded form, and weight changes are reported without confidence intervals, so precision cannot be judged from the abstract.
• The 17-week off-treatment period is short, so it does not show what happens to weight or blood sugar over a longer time off the medicine.
• Numbers from this trial should not be placed next to those from other medicines' diabetes-prevention studies to rank them.
• We reviewed the abstract only, so how missing data were handled over three years was not checked.
• The trial was funded by the manufacturer.

What it means in Canada

For Canadian readers with prediabetes, this is the longest randomized evidence on tirzepatide, and it links continued treatment with fewer new diabetes diagnoses over three years. It does not describe how the medicine is prescribed or paid for here. See tirzepatide in Canada, public drug coverage by province and compare services.

Related reading

Other studies in this library that bear on the same question.

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