Tirzepatide for 3 Years in People With Obesity and Prediabetes: Progression to Diabetes 1.3% vs 13.3%

Results of a phase 3 trial showed that giving tirzepatide, which acts on both the GLP-1 and GIP hormone receptors, for more than three years greatly reduced progression to type 2 diabetes compared with placebo in people who had both obesity and prediabetes. They were published in the New England Journal of Medicine (NEJM). This is the 3-year analysis of the SURMOUNT-1 trial, led by researchers at Yale School of Medicine in the United States.

1,032 people with prediabetes, 176 weeks of treatment followed by 17 weeks off drug

SURMOUNT-1 enrolled 2,539 adults with obesity, who were randomly assigned to once-weekly tirzepatide 5, 10 or 15 mg or placebo. This analysis covers 1,032 of them who also had prediabetes, treated for 176 weeks and then observed for 17 weeks off the drug.

At week 176, body weight had fallen by 12.3%, 18.7% and 19.7% by dose, compared with 1.3% in the placebo group. Over the same period, type 2 diabetes was diagnosed in 1.3% of the tirzepatide group and 13.3% of the placebo group (hazard ratio 0.07). After 17 weeks off treatment, the figures were 2.4% and 13.7%, so the difference was maintained, but the share diagnosed in the treated group rose somewhat. The most common adverse events were gastrointestinal symptoms, mostly mild to moderate and concentrated in the first 20 weeks while the dose was being raised.

Durability of the preventive effect remains a question

The study is significant in confirming over a long period, in a drug trial, that weight loss can delay the onset of diabetes. However, diagnoses of diabetes increased even in the short period after the drug was stopped, so further confirmation is needed of how much the effect depends on continued treatment. The trial was funded by the developer.