A cardiovascular outcomes trial (CVOT) is a randomized study — usually thousands of participants followed for several years — whose primary question is whether a medication changes the rate of real cardiovascular events (MACE), not just whether it improves a number like A1c or body weight. The FDA began requiring CVOTs for new diabetes drugs in 2008 after safety concerns with an earlier medication, which is why every major GLP-1 has one.
CVOTs are the reason the heart-benefit claims for GLP-1s carry weight: LEADER (liraglutide), SELECT (semaglutide in obesity without diabetes), REWIND (dulaglutide), and SURPASS-CVOT (tirzepatide versus dulaglutide) are all CVOTs. Because these trials enroll people at high cardiovascular risk, their results apply most directly to that group. See the cardiovascular benefits of GLP-1 medications.