Despite some early concerns, investigators have confirmed that canagliflozin does not increase the risk for hyperkalemia.

Preliminary studies and interim data from the CANagliflozin cardioVascular Assessment Study (CANVAS) had suggested that canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, might increase serum potassium, particularly at the 300 mg dose, in patients with renal impairment. To assess real risk, Matthew R. Weir, MD, of the University of Maryland School of Medicine in Baltimore, Maryland, and colleagues analyzed final data from the CANVAS and CANVAS-Renal trials involving 10,142 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) higher than 30 mL/min/1.73 m2. Approximately 80% of patients also were taking renin-angiotensin-aldosterone system (RAAS) inhibitors.

Mean serum potassium levels were consistent and comparable over time in the canagliflozin and placebo groups, including by baseline eGFR (ie, 60 or more, 45 to less than 60, and 45 or less mL/min/1.73 m2), Dr Weir’s team reported in Clinical Kidney Journal. Canagliflozin recipients did not have significantly greater risks for increased or decreased serum potassium. Results did not differ by baseline eGFR, canagliflozin dose (100 or 300 mg), or use of RAAS inhibitors.

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Further, hyperkalemia events appeared uncommon and occurred at similar rates in the canagliflozin and placebo group (6.9 vs 4.4 per 1000 patient-years, respectively) within the main CANVAS study. Across both CANVAS trials, serious hyperkalemia events occurred in just 0.4 vs 0.6 per 1000 patient-years, respectively.

Based on data from the completed CANVAS Program, the hyperkalemia warning was removed from the drug label in October 2018.

Dr Weir’s team noted that “the results of our analyses using data from the completed CANVAS Program provide encouragement that, from a safety standpoint, there are no apparent changes in serum potassium that could interfere with the use of canagliflozin in patients with [type 2 diabetes mellitus] and moderately impaired renal function whether used with or without RAAS inhibitors, though only 5% of participants had a baseline eGFR <45 mL/min/1.73m2.”

Disclosure: This clinical trial was supported by Janssen Global Services. Please see the original reference for a full list of authors’ disclosures.


Weir MR, Slee A, Sun T, et al. Effects of canagliflozin on serum potassium in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. Clin Kid J. doi:10.1093/ckj/sfaa133