Effects of sodium glucose cotransporter 2 inhibitors on the risk of hyperkalemia in patients on mineralocorticoid receptor antagonist: a systematic review and meta-analysis

Type of funding sources: None.

Occurrence of hyperkalemia has been a great limitation in the full implementation of a guideline-directed medical therapy especially in patients with heart failure. Recent developments have exhibited the positive role of SGLT2 inhibitors, not only on the cardiovascular outcomes but also conferred renal protection.

We explored the effects of SGLT2i and MRA combination on the risk of developing hyperkalemia.

Randomized controlled trials on SGLT2i versus placebo in patients already on MRA regardless of heart failure status reporting outcomes of potassium homeostasis were searched using Pubmed, CENTRAL, and ScienceDirect. Outcome of interest was the effects on the risk of hyperkalemia. Pooled hazard ratios with 95% confidence intervals were used as effect estimates using fixed-effects model.

Five studies were included with a total of 11,123 patients. There was a significant reduction on the risk of hyperkalemia in the MRA with SGLT2i group (HR 0.61, 95% CI 0.50-0.75, p<0.00001) compared to MRA without SGLT2i group.

SGLT2i provides significant risk reduction on the development of hyperkalemia in patients already on a mineralocorticoid receptor antagonist.