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Preclinical studies have identified that GLP-1 analogs such as exendin-4 and GLP-1RAs have direct anti-atherosclerotic and anti-inflammatory effects that may contribute to their cardio- and neuroprotective nature.[42] GLP-1RAs can also directly interact with cardiomyocytes, inducing receptor-mediated ischemic conditioning that decreases myocardial infarct size in test animals receiving GLP-1RAs.[43] Similar effects were noted in rodent brains, with liraglutide reducing cerebral infarct volume in rats.[42] Randomized clinical trials (RCTs) also identified that exenatide similarly reduced myocardial infarct size and liraglutide reduced the resulting necrotic area in human patients following a MI.[43] This may account for the reduced need for coronary revascularization in patients on GLP-1RAs.[12] Despite the findings of overall improvements to composite cardiovascular outcomes, GLP-1RAs showed a non-significant trend toward reducing MI risk and did not affect rates of hospitalization for unstable angina in patients with diabetes.[12] These agents tend to have a stronger effect on stroke reduction in such patients, highlighting the complexity and variability of cardiovascular disease and its sequelae

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