Effects of canagliflozin on end-stage kidney disease and cardiovascular mortality in adults aged 50 years or older: an individual participant data meta-analysis of the CANVAS and CREDENCE trials.

Sodium-glucose co-transporter 2 inhibitors have demonstrated cardiorenal benefits across diverse populations. We evaluated the effect of canagliflozin on cardiovascular mortality and end-stage kidney disease in participants aged 50 years or older randomised in the CANVAS and CREDENCE trials, through a two-stage individual participant data meta-analysis of harmonised subject-level datasets obtained from the Yale University Open Data Access Project. Age-tertile-stratified Cox proportional hazards models were the primary analysis; trial-level log-hazard ratios were combined using restricted maximum likelihood. The number needed to treat at 3 years was derived from Kaplan-Meier estimates. We included 3,955 CANVAS and 4,035 CREDENCE participants. For cardiovascular mortality (309 events), trial-level hazard ratios were 0.874 (95% confidence interval 0.623-1.226) and 0.814 (0.596-1.113); the pooled hazard ratio was 0.841 (0.669-1.058). For end-stage kidney disease (175 events), hazard ratios were 0.853 (0.250-2.916) and 0.518 (0.376-0.714; p < 0.001); the pooled hazard ratio was 0.535 (0.392-0.729). The number needed to treat at 3 years for end-stage kidney disease was 27.5 in CREDENCE. Among these trial participants, canagliflozin produced a clinically meaningful, statistically significant 46.5% reduction in end-stage kidney disease. The effect on cardiovascular mortality was favourable but not statistically significant, likely reflecting limited power.