Abstract 16589: Predicting Cardiovascular Risk in Participants Treated With Tirzepatide in the SURPASS 1-5 Trials

Abstract

Predicting atherosclerotic cardiovascular disease (ASCVD) risk considers factors that individually influence the likelihood of experiencing a major cardiovascular (CV) event. Tirzepatide (TZP) is a GIP and GLP-1 receptor agonist that improved risk factors such as lipid profile and systolic blood pressure across the Phase 3 SURPASS T2D program. We compared the effect of TZP versus the comparator on calculated ASCVD risk from baseline to endpoint in each of the 5 SURPASS (S) studies. We assessed the ASCVD risk in T2D participants without CVD history from S 1-5 studies using an American College of Cardiology/American Heart Association risk engine. The risk engine considers the factors: sex, age, race, total cholesterol, high density lipoprotein, systolic blood pressure, antihypertensive medication use, smoking and diabetes status. Risk scores and categories are summarized by treatment group. The baseline characteristics vary between studies (female sex ranges from 44.9% to 54.6%, mean age in years ranges from 53.6 to 64.3) but were similar among treatment groups within each study. The median baseline risk score across the TZP dose range were 6.5-11.5 for S-1, 9.3-10.8 for S-2, 12.4-15.4 for S-3, 22.9-26.0 for S-4, and 14.8-19.1 for S5. At the primary endpoint (40 or 52 Weeks), the ASCVD risk category for 10.9-21.4% of TZP-treated participants improved versus 2.9-12.7% for placebo/comparator (Table). Also, the risk category for 1.2-9.4% of TZP-treated participants worsened versus 6.3-14.9% for placebo/comparator. The median CV risk score was decreased in all TZP treatment groups while the median CV risk score was increased in the placebo/basal insulin groups. In SURPASS-2, the decreases in CV risk score were qualitatively greater in the TZP groups compared to the semaglutide group. TZP treatment lowers CV risk and significantly more participants shift to a lower CV risk category when compared to placebo, basal insulins, and semaglutide.