Giugliano D, et al. - Researchers intended to clarify the significance of glycemic control and preexisting cardiovascular disease in assessing the risk of major cardiovascular events (MACE) in patients with type 2 diabetes mellitus. For this purpose, they analyzed cardiovascular outcome trials categorizing patients with or without preexisting cardiovascular disease. Only in patients with cardiovascular disease at baseline did findings reveal a lower risk of MACE. A significant 14% lower MACE risk in patients with preexisting cardiovascular disease and with a nonsignificant 2% higher MACE risk in those without preexisting cardiovascular disease correlated with the use of both glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors correlated vs placebo. In the treatment of patients with type 2 diabetes mellitus and overt cardiovascular disease, inclusion of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists is recommended, with attention paid to improving glycemic control, which could augment their advantage on MACE.