Mineralocorticoid Receptor Antagonists in the Treatment of Diabetic Kidney Disease: Their Application in the Era of SGLT2 Inhibitors and GLP-1 Receptor Agonists.

Abstract

Purpose of review: This review focuses on new clinical data involving a novel class of drugs, nonsteroidal mineralocorticoid receptor antagonists (NS-MRAs), specifically, finerenone and its effects on cardiovascular and diabetic kidney disease outcomes.

Recent findings: NS-MRAs are a novel class of agents for treating diabetic kidney disease (DKD). While they are chemically and pharmacologically distinct from steroidal MRAs (spironolactone, eplerenone), they effectively inhibit the MR receptor differently. Inhibition of MR receptor activation reduces inflammatory and profibrotic pathways involving the cardiorenal/vascular systems. Small diabetic kidney disease (DKD) clinical studies demonstrate that steroidal MRAs reduce albuminuria relative to placebo, although hyperkalemia is a major adverse event that has precluded large outcome trials. The NS-MRA, finerenone, demonstrated slowed progression of DKD and reduction of cardiovascular death primarily driven by reduced heart failure incidence in two separate randomized controlled clinical trials (FIDELIO and FIGARO). Use of NS-MRAs, therefore, provides a third "pillar of therapy" to reduce cardiorenal events added to blockers of the renin-angiotensin system and SGLT2 inhibitors. If the pending outcome trial, FLOW, is positive, potentially, GLP1-RAs may also be part of this "pillar" structure.