Since 2013 several placebo-controlled cardiovascular outcomes trails on new classes of glucose-lowering agents in addition to standard care have been reported. These trails were designed to demonstrate non-inferiority to placebo with regard to cardiovascular safety for patients with type 2 diabetes mellitus at high cardiovascular risk.For the glucagon-like peptide 1 (GLP-1)-receptor agonists liraglutide and semaglutide as well as for the sodium-glucose cotransporter-2 (SGLT-2) inhibitors empagliflozin and canagliflozin statistically significant reductions of the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were demonstrated. Cardiovascular outcomes trails for the dipeptidyl peptidase-4 (DPP-4) inhibitors saxagliptin, alogliptin, and sitagliptin did not show statistically significant differences for major cardiovascular events between treatment and placebo groups.Therefore, for patients with established cardiovascular disease who do not achieve sufficient blood glucose control on metformin monotherapy GLP-1-receptor agonists and SGLT-2 inhibitors should be favoured for diabetes therapy intensification. However, the use of DPP-4 inhibitors should be considered for patients who are in need of a well-tolerated and safe oral glucose-lowering therapy.