CANVAS Program - Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

Last edited 10/2018 and last reviewed 05/2021

CANVAS Program - Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes


CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk

  • participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks
  • primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke
  • the CANVAS Program was a prespecified plan for the integrated analyses of the CANVAS and CANVAS-R trials (1,2)

Results:

  • mean age of the participants was 63.3 years, 35.8% were women
  • mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease
  • rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority)
  • the primary cardiovascular outcome for the CANVAS and CANVAS-R studies individually did not reach significance. However for the CANVAS Program the primary cardiovascular endpoint did reach significance


  • although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77)
  • adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal

The study authors concluded:

  • "...in two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal..."

Key findings:

  • CANVAS Program met its primary objective of demonstrating the cardiovascular safety and efficacy of canagliflozin
  • canagliflozin use was associated with an increased risk of amputation which should be taken into consideration when prescribing this agent
  • data suggest a favorable benefit/risk profile with canagliflozin treatment in many patients with type 2 diabetes and high cardiovascular risk

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