Canagliflozin has no substantial effect on serum potassium levels: CANVAS program

In past studies, sodium-glucose cotransporter 2 inhibitor canagliflozin has been shown to reduce the risk of cardiovascular and renal events in patients with Type 2 diabetes mellitus and high risk. Pooled analyses of data from early studies and interim data from the CANagliflozin Cardiovascular Assessment Study (CANVAS) suggested that canagliflozin might lead to increases in serum potassium, particularly the 300 mg dose in patients with renal impairment, which is important because high serum potassium is associated with increased cardiovascular and renal risk. A study was conducted by a group of researchers in U.S.A. to study the effect of canagliflozin on serum potassium levels and hyperkalemia rates in the completed CANVAS Program.

The CANVAS Program included a total of 10,142 participants and was comprised of two comparable double-blind, randomized, placebo-controlled trials (CANVAS and CANVAS-Renal). Participants received canagliflozin 100 or 300 mg or a placebo. Serum potassium measurements were performed in a central laboratory and assessed at 6- month intervals.

The results of the study are as follows:

• In the CANVAS Program, mean potassium levels were generally consistent with canagliflozin and placebo, overall and by baseline estimated glomerular filtration rate.
• The risk of increased or decreased potassium was similar with canagliflozin and placebo overall and by baseline eGFR or use of renin–angiotensin–aldosterone system inhibitors; levels did not appear different by canagliflozin dose.
• Hyperkalemia and serious hyperkalemia adverse events were not different across groups.

The researcher concluded that in the CANVAS Program, there were no meaningful effects of canagliflozin on serum potassium in the overall population or key subgroups. Hyperkalemia adverse events were uncommon and occurred at comparable rates with canagliflozin and placebo.

Reference:

Effects of canagliflozin on serum potassium in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program by Weir M et. al published in the Clinical Kidney Journal.

https://doi.org/10.1093/ckj/sfaa133