Canagliflozin Has Kidney-Protective Effects In Patients With
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The Canagliflozin and Renal Events in Diabetes with Established Nephropathy 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 less than 30 ml/min per 1.73 m2. The participants in the CREDENCE study had type 2 diabetes mellitus, a urinary albumin-creatinine ratio greater than 300–5000 mg/g, and an eGFR of 30 to 90 ml/min per 1.73 m2 at screening. This post hoc analysis evaluated participants with eGFR <30 ml/min per 1.73 m2 at randomization.

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, 174 of 4401 (4%) participants had an eGFR less tha 30 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.

-- Effects of canagliflozin on kidney, cardiovascular, and mortality outcomes were consistent for those with eGFR <30 and greater than 30 ml/min per 1.73 m2.

-- The estimate for kidney failure in participants with eGFR less than 30 ml/min per 1.73 m2 was similar to those with eGFR greater than 30 ml/min per 1.73 m2.

-- There was no imbalance in the rate of kidney-related adverse events or AKI associated with canagliflozin between participants with eGFR less than 30 and greater than 30 ml/min per 1.73 m2.

Conclusively, this post hoc analysis suggests canagliflozin slowed progression of kidney disease, without increasing AKI, even in participants with eGFR less than 30 ml/min per 1.73 m2.

Source: https://cjasn.asnjournals.org/content/early/2020/11/18/CJN.10140620
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