Researchers examined the cardiovascular safety of degludec, an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. They randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). Adjudicated severe hypoglycemia was the prespecified, multiplicity-adjusted secondary outcome. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group. At 24 months, the mean glycated hemoglobin level was 7.5 plus or minus 1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group. Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group. Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events.