PURPOSE: The cardiovascular safety outcomes of newer antidiabetic agents were reviewed. SUMMARY: Seven randomized, placebo-controlled trials involving patients with type 2 diabetes mellitus with or at risk for cardiovascular disease were reviewed. The trials examined the cardiovascular safety outcomes of the following agents: alogliptin, saxagliptin, and sitagliptin (dipeptidyl peptidase-4 [DPP-4] inhibitors); liraglutide, lixisenatide, and semaglutide (glucagon-like peptide-1 agonists); and empagliflozin (a sodium glucose cotransport-2 inhibitor). The DPP-4 inhibitor and lixisenatide trials showed a neutral effect on cardiovascular events (composite of cardiovascular death, myocardial infarction, or stroke, with or without unstable angina). Empagliflozin showed a significant reduction in cardiovascular events, cardiovascular death, all-cause death, and hospitalization due to heart failure (HF); liraglutide reduced cardiovascular events, cardiovascular death, and all-cause death, and semaglutide reduced cardiovascular events and nonfatal stroke. Most studies showed a neutral effect of the drug on hospitalization for HF; however, saxagliptin and alogliptin (in the subgroups of patients without a history of HF) showed a significant increase while empagliflozin showed a significant reduction in hospitalizations for HF. The data for empagliflozin, liraglutide, and semaglutide are compelling; however, further studies are necessary to confirm observed benefits and better characterize long-term safety and their use as a strategy to reduce cardiovascular events. CONCLUSION: A review of cardiovascular safety outcomes for new antidiabetic agents found that saxagliptin and alogliptin were associated with an increase in hospitalization for HF. The data for empagliflozin, liraglutide, and semaglutide showed a reduction in cardiovascular events and death or a neutral effect on cardiovascular endpoints.