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Tirzepatide and the 10‐year predicted risk of cardiovascular disease and type 2 diabetes in adults with obesity and prediabetes: A post hoc analysis from the three‐year <scp>SURMOUNT</scp> ‐1 trial

Emily R. Hankosky, Jérémie Lebrec, Clare J. Lee, Georgios K. Dimitriadis, Irina Jouravskaya, Adam Stefański, W. Timothy Garvey

2025Diabetes Obesity and Metabolism10 citationsDOIOpen Access PDF

Abstract

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Topics & Concepts

MedicineType 2 diabetesPost-hoc analysisObesityDiseaseInternal medicineDiabetes mellitusType 2 Diabetes MellitusAtherosclerotic cardiovascular diseasePhysical therapyClinical trialRisk factorPost hocMEDLINERisk assessmentWeight lossBaseline (sea)GerontologyCohort studyBlood Pressure and Hypertension StudiesLipoproteins and Cardiovascular HealthDiabetes Treatment and Management
Tirzepatide and the 10‐year predicted risk of cardiovascular disease and type 2 diabetes in adults with obesity and prediabetes: A post hoc analysis from the three‐year <scp>SURMOUNT</scp> ‐1 trial | Litcius