Sodium glucose co-transporter 2 inhibition is a novel mode of treatment for type 
2 diabetes mellitus (T2DM). The sodium glucose co-transporter 2 inhibitor 
canagliflozin lowered blood glucose, blood pressure, and body weight, with 
increased risk of urogenital infections in Phase 2 studies. Effects on 
macrovascular complications of diabetes remain to be determined. CANVAS is a 
double-blind, placebo-controlled trial designed to evaluate the effects of 
canagliflozin on the risk of cardiovascular disease and to assess safety and 
tolerability in patients with inadequately controlled T2DM and increased 
cardiovascular risk. The first of 2 planned phases randomized 4,330 individuals 
to placebo, canagliflozin 100 or 300 mg (1:1:1) with planned follow-up of about 
2 years to substantiate potential cardiovascular protection by assessing key 
biomarkers and to achieve initial safety objectives. By the end of mid-September 
2012, a total of 7174 patient-years of follow-up were accrued. Mean baseline age 
was 62 years, duration of diabetes 13 years; hemoglobin A1c 8.2%, fasting plasma 
glucose 9.3 mmol/L, and body mass index 32 kg/m(2). Of the participants, 34% are 
female and 57% had a history of atherosclerotic vascular disease. Participants 
will be followed up to achieve primary safety and tolerability objectives and to 
investigate secondary outcomes. The planned second phase will not be undertaken. 
CANVAS will define the effects of canagliflozin on biomarkers and provide data 
on cardiovascular safety against established regulatory parameters.