Canagliflozin Reduces Risk of Hyperkalaemia in T2DM and CKD

The use of canagliflozin reduces the risk of hyperkalaemia in people with type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) without increasing the risk of hypokalaemia, suggests a study published in the European Heart Journal.

Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin–aldosterone system, particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain.

Neuen B et. al. conducted the CREDENCE trial wherein they randomized 4401 participants with T2DM and CKD to the SGLT2 inhibitor canagliflozin or matching placebo. In this post hoc analysis using an intention-to-treat approach, they assessed the effect of canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders.

They also analysed effects on central laboratory-determined hyper- and hypokalaemia and change in serum potassium.

At baseline, the mean serum potassium in canagliflozin and placebo arms was 4.5 mmol/L; 4395 (99.9%) participants were receiving renin-angiotensin system blockade.

Study Results

• The incidence of investigator-reported hyperkalaemia or initiation of potassium binders was lower with canagliflozin than with placebo.
• Canagliflozin similarly reduced the incidence of laboratory-determined hyperkalaemia, with no effect on the risk of hypokalaemia.
• The mean serum potassium over time with canagliflozin was similar to that of placebo.

Thus, the researchers concluded that among patients treated with renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia.

Reference

A study titled, "Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial" by Neuen B et. al. published in the European Heart Journal.
https://doi.org/10.1093/eurheartj/ehab497