In a three‑year study, people with obesity and pre‑diabetes who took the weekly peptide tirzepatide saw their 10‑year chances of heart disease and diabetes drop a lot, especially at higher doses, while those on placebo actually got riskier.

We assessed the association between tirzepatide and the 10-year predicted risk of developing cardiovascular disease (CVD) and type 2 diabetes (T2D) among three-year SURMOUNT-1 trial participants. This post hoc analysis applied validated risk engines that predict 10-year CVD (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], and total CVD) and T2D risk to the three-year SURMOUNT-1 clinical trial data at baseline and 176 weeks. In the trial, participants with obesity and prediabetes at baseline were randomly assigned to once weekly tirzepatide (5/10/15 mg) or placebo for 176 weeks of treatment. Changes in risk scores from baseline to week 176 were compared between tirzepatide and placebo using a mixed model of repeated measures. Tirzepatide treatment was associated with greater reductions in the 10-year predicted risk of CVD and T2D compared with placebo. Mean percent change from baseline to week 176 in predicted ASCVD risk score was greater in tirzepatide-treated groups using the ACC/AHA (5 mg: -4.6%; 10 mg: -7.5%; 15 mg: -9.2%) and PREVENT risk equations (5 mg: -3.7%; 10 mg: -6.3%; 15 mg: -8.8%) versus increased risk in placebo (57.9% and 40.5%, respectively; p < 0.0001 for all). Mean absolute change in T2D risk scores from baseline to week 176 using Cardiometabolic Disease Staging (CMDS) was greater in tirzepatide-treated groups (5 mg: -17.0%; 10 mg: -19.6%; 15 mg: -19.5%) versus placebo (-4.3%, p < 0.0001). Tirzepatide treatment was associated with a reduction in the 10-year predicted risk of both cardiovascular outcomes and T2D in people with obesity and prediabetes.