In this post hoc analysis of the SURMOUNT-1 trial, the estimated risk of developing type 2 diabetes was compared between treatment with the dual GIP/GLP-1 receptor agonist tirzepatide and placebo.
A total of 2539 people with BMI ≥30 kg/m2 (95% of participants) or BMI ≥27 kg/m2 plus one or more weight-related complication, but without type 2 diabetes, were randomised to tirzepatide (5, 10 or 15 mg) or placebo. The validated Cardiometabolic Disease Staging risk engine was used to estimate the 10-year risk of type 2 diabetes (based on age, sex, race, waist circumference, fasting glucose, blood pressure and lipid levels) at baseline and after 6 and 18 months of treatment.
The estimated 10-year risk of type 2 diabetes was similar between the tirzepatide and placebo groups at baseline, ranging from 22.9% to 24.3%. At 6 months, the risk fell to 11.0–12.5% in the tirzepatide groups (greater reductions seen with higher doses), versus 21.4% in the placebo group. At 18 months, estimated risk had fallen further in the tirzepatide groups, to 9.0–11.4%, compared to 23.0% with placebo. Median relative risk reductions at 18 months were 60.3–69.0% for the tirzepatide groups versus 10.8% for the placebo group.
At baseline, 40% of participants had pre-diabetes. The effect of tirzepatide use was significantly greater in participants with pre-diabetes, with placebo-adjusted risk reductions of 13.4–17.7% at 18 months, than in those with normoglycaemia (placebo-adjusted reductions of 10.7–11.8%). Subgroup analysis according to baseline BMI were consistent with the primary analysis.
The authors conclude that tirzepatide reduced the predicted relative risk of type 2 diabetes by about half at week 24 and by about two-thirds at week 72. The study was limited by the use of 10-year estimations of risk rather than hard outcomes; however, the ongoing SURMOUNT-1 study extension and the SURMOUNT-MMO trial will provide direct evidence on the impact of tirzepatide on progression from pre-diabetes to type 2 diabetes in the future.