Cardiovascular (CV) disease remains the leading cause of death in people with 
diabetes, highlighting the importance of using treatment options that do not 
increase CV risk or possibly decrease CV outcomes. Since 2008, the Food and Drug 
Administration has required demonstration of CV safety for all new medications 
developed for the glycemic management of diabetes. Seven trials have been 
published that have established CV safety for three DPP-4 inhibitors 
(alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists 
(liraglutide, lixisenatide, and semaglutide), and one sodium-glucose 
cotransporter-2 inhibitor (empagliflozin). Three of those studies also 
established superiority with liraglutide, empagliflozin, and semaglutide at 
reducing the composite primary endpoint of major CV events (CV death, nonfatal 
myocardial infarction, and nonfatal stroke). In addition, one trial found an 
increase in heart failure hospitalizations with saxagliptin. The findings of 
these trials must be compared and contrasted cautiously given the differences in 
patient populations and trial designs, but together they provide important 
information that can be used to shape our treatment guideline recommendations 
and patient-specific treatment decisions.