Cardiovascular outcomes with canagliflozin - is it on the CANVAS?

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (the 'gliflozins') promote the excretion of glucose from the kidney to lower HbA1c. Empagliflozin was the first gliflozin shown to improve cardiovascular and renal outcomes in subjects with type 2 diabetes and cardiovascular disease. Areas covered: In the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, there were improvements in the primary cardiovascular and exploratory renal outcomes with canagliflozin, compared to placebo. The safety outcome finding, which was of most interest, was that there was a higher risk of amputation of toes, feet, or legs with canagliflozin than in the placebo group. This program is the subject of this evaluation. Expert opinion: As canagliflozin has small beneficial effects in the treatment of type 2 diabetes in subjects with cardiovascular disease, it is not on the canvas. However, there are still several questions about canagliflozin that need to be answered before it is widely used, especially in comparison with other gliflozins; As amputations have only been reported with canagliflozin in CANVAS, should other gliflozins be preferred? As canagliflozin has not been shown to be beneficial in subjects not taking diuretics, should other gliflozins be preferred in this population? Clarification is also needed as to whether canagliflozin increases the risk of non-fatal stroke, or not.