Effects Of Canagliflozin In Patients With Baseline Egfr < 30 Ml/Min Per 1.73 M(2) Subgroup Analysis Of The Randomized Credence Trial

Clinical Evaluation (CREDENCE) trial demonstrated that the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of kidney failure and cardiovascular events in participants with type 2 diabetes mellitus and CKD. Little is known about the use of SGLT2 inhibitors in patients with eGFR<30ml/min per 1.73m(2). The participants in the CREDENCE study had type 2 diabetes mellitus, a urinary albumin-creatinine ratio >300-5000 mg/g, and an eGFR of 30 to <90 ml/min per 1.73 m(2) at screening. This post hoc analysis evaluated participants with eGFR <30 ml/min per 1.73 m(2) at randomization. Design, setting, participants, & measurements Effects of eGFR slope through week 130 were analyzed using a piecewise, linear, mixed-effects model. Efficacy was analyzed in the intention-to-treat population, on the basis of Cox proportional hazard models, and safety was analyzed in the on-treatment population. At randomization (an average of 29 days after screening), 174 of 4401 (4%) participants had an eGFR<30ml/min per 1.73m(2) (mean [SD] eGFR, 26 [3] ml/min per 1.73 m2). Results From weeks 3 to 130, there was a 66% difference in the mean rate of eGFR decline with canagliflozin versus placebo (mean slopes, -1.30 versus -3.83ml/min per 1.73m(2) per year; difference, -2.54 ml/min per 1.73m(2) per year; 95% confidence interval [CI], 0.90 to 4.17). Effects of canagliflozin on kidney, cardiovascular, and mortality outcomes were consistent for those with eGFR<30 and >= 30 ml/min per 1.73 m(2) (all P interaction >0.20). The estimate for kidney failure in participants with eGFR,30 ml/min per 1.73m2 (hazard ratio, 0.67; 95% CI, 0.35 to 1.27) was similar to those with eGFR >= 30 ml/min per 1.73 m(2) (hazard ratio, 0.70; 95% CI, 0.54 to 0.91; P interaction=0.80). There was no imbalance in the rate of kidney-related adverse events or AKI associated with canagliflozin between participants with eGFR<30 and >30 ml/min per 1.73 m(2) (all P interaction >0.12). Conclusions This post hoc analysis suggests canagliflozin slowed progression of kidney disease, without increasing AKI, even in participants with eGFR,30 ml/min per 1.73 m(2).