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ABSTRACT
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.
Declaration of interest
R Guthrie has acted as a speaker for Janssen pharmaceuticals. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. One of the peer reviewers of this manuscript had previously received grant support from Boehringer Ingelheim. Two additional peer reviewers on this manuscript had no relevant financial relationships to disclose.