Herein we will summarize the data from CVOTs relating to MI in the T2DM population treated with SGLT2 inhibitors or GLP-1R agonists, while interrogating preclinical data to delineate mechanisms that may account for either SGLT2 inhibitor or GLP-1R agonist mediated cardioprotection against ischemic heart disease. Here, GLP1R is linked to type 2 diabetes mellitus.