Patients with type 2 diabetes mellitus have an increased risk of cardiovascular and renal disease. The CANVAS Program Collaborative Group sought to determine the cardiovascular safety and efficacy of canagliflozin, a sodium–glucose cotransporter 2 inhibitor, by combining data from two trials (CANVAS and CANVAS-R) involving 667 centres across 30 countries. In both trials, patients were randomly assigned to receive canagliflozin or placebo. In total, 9,734 participants completed the trial in which they were enrolled. The primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke occurred less frequently in the canagliflozin group than in the placebo group. Furthermore, patients who received canagliflozin had a lower risk of hospitalization for heart failure and progression of albuminuria than those who received placebo. Notably, patients receiving canagliflozin had a greater risk of amputation, an observation that requires further investigation in future studies.