The sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin may reduce the risk for hyperkalemia in patients with diabetes and chronic kidney disease (CKD) treated with renin-angiotensin-aldosterone system (RAAS) inhibitors, investigators reported.
In The CREDENCE trial, investigators randomly assigned 4401 patients with type 2 diabetes and CKD to receive canagliflozin or placebo. Virtually all patients received maximum tolerated RAAS blockade. At baseline, the mean serum potassium level was 4.5 mmol/L.
In a post hoc analysis, canagliflozin was associated with lower incidence of a composite primary outcome of investigator-reported hyperkalemia or initiation of potassium binders: 32.7 vs 41.9 patients per 1000 patient-years. Canagliflozin treatment significantly reduced the risk for the composite primary outcome by 22% compared with placebo, Hiddo J.L. Heerspink, PhD, PharmD, of the University of Groningen in the Netherlands, and colleagues reported in European Heart Journal. Canagliflozin also significantly reduced the incidence of laboratory-determined hyperkalemia (defined as serum potassium 6.0 mmol/L or more) by 23%, without significantly increasing the risk for hypokalemia (defined as serum potassium less than 3.5 mmol/L). Use of potassium-sparing diuretics and mineralocorticoid receptor antagonists were similar between groups and did not explain the outcomes. Over time, mean serum potassium increased similarly in both groups, likely reflecting declining kidney function.
Dr Heerspink’s team concluded that “canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without any adverse effect on incident hypokalaemia.” They suggested that SGLT2 inhibitors may enable greater use of RAAS blockade and mineralocorticoid receptor antagonists in CKD and/or heart failure. Whether the purported benefits would apply to patients with nondiabetic CKD is uncertain, the investigators noted. Prospective studies are still needed to confirm the findings and determine mechanisms of action.
Disclosure: The CREDENCE study was supported by Janssen Research & Development. Please see the original reference for a full list of disclosures.
Neuen BL, Oshima M, Perkovic V, et al. Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial. Eur Heart J. doi:10.1093/eurheartj/ehab497