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.