Canagliflozin and cardiovascular and renal events in type 2 diabetes

Review of: Neal B, Perkovic V, Mahaffey K, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-657. The report combines the data from two trials, CANVAS and CANVAS-Renal, which were designed to evaluate the safety and effect of canagliflozin, an SGLT-2 inhibitor, on the appearance of cardiovascular and renal events in patients with type 2 diabetes. Enrollees were patients with type 2 diabetes of at least 30 years of age, with a glycated hemoglobin of > or equal to 7.0% and < or equal to 10.5%. Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease, and to have an estimated glomerular filtration rate (eGFR) of >30 ml/min. Patients were randomized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS, and to canagliflozin 100 mg with a possible increase to 300 mg, or placebo, in CANVAS-Renal. Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practices in their community. There was a significant 14% reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in the canagliflozin treated patients. There was also a pattern of improvement in markers of renal disease, including the change in the level and nature of albuminuria, a 40% decrease in the glomerular filtration rate, the need for renal replacement therapy, or death from renal causes. This study expands the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study, raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most, if not all, type 2 diabetes patients, not only to control hyperglycemia but also to reduce cardiovascular and renal events.