Table 5

Risk reduction in four completed trials showing evidence of CV benefit

LEADER (10)SUSTAIN-6 (11)EMPA-REG OUTCOME (13,60)CANVAS Program (14)
Subjects (n)9,3403,2977,02010,142
Mean age (years)64.364.663.163.3
Diabetes duration (years)*12.813.957% >1013.5
Mean baseline A1C (%)
Mean placebo-corrected A1C difference (%)−0.4−0.7 (0.5 mg dose)−0.24 (10 mg dose)−0.58
−1.0 (1.0 mg dose)−0.36 (25 mg dose)
Median follow-up duration (years)
3-point MACE RRR (%)13261414
3-point MACE ARR (%)
CV death RRR (%)222384§; 13
Nonfatal MI RRR (%)12261315
Nonfatal stroke RRR (%)1139+2410
All-cause mortality RRR (%)15+53213§; 10
HF hospitalization RRR (%)13+113533
Worsening nephropathy RRR (%)22363940
  • Boldface type indicates statistical significance. +, increased relative risk; —, not reported; ARR, absolute risk reduction; RRR, relative risk reduction.

  • *Reported as mean in all trials except EMPA-REG OUTCOME, which reported percentage of population with diabetes duration >10 years.

  • †For LEADER and the CANVAS Program, difference was updated over time; for SUSTAIN-6 and EMPA-REG OUTCOME, difference was at study end.

  • ‡Data needed to calculate ARR in 3-point MACE (specifically the NNT) were not reported for the CANVAS Program; instead this trial reported an incidence rate difference of 4.6 per 1,000 patient-years for canagliflozin vs. placebo.

  • §Truncated integrated data set (refers to pooled data from CANVAS after 20 November 2012 plus CANVAS-R; prespecified in treating hierarchy as the principal data set for analysis for superiority of all-cause mortality and CV death in the CANVAS Program).

  • ‖Nontruncated integrated data (refers to pooled data from CANVAS, including before 20 November 2012 plus CANVAS-R.

  • ¶Worsening nephropathy is defined as the new onset of macroalbuminuria (urine albumin creatinine ratio >300 mg/g) or a doubling of the serum creatinine level and an eGFR rate of ≤45 mL/min/1.73 m2, the need for continuous renal-replacement therapy, or death from renal disease in LEADER, SUSTAIN, and EMPA-REG OUTCOME and as 40% reduction in eGFR, renal-replacement therapy, or death from renal causes in CANVAS. This outcome was a prespecified exploratory adjudicated outcome in LEADER, SUSTAIN-6, and CANVAS but not in EMPA-REG OUTCOME.