Finerenone: Questions and Answers—The Four Fundamental Arguments on the New-Born Promising Non-Steroidal Mineralocorticoid Receptor Antagonist

Abstract

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high, and diabetes remains the leading cause of end-stage kidney disease in affected patients. To date, current medications for CKD and type 2 diabetes mellitus have not reset residual risk in patients due to a high grade of inflammation and fibrosis contributing to kidney and heart disease. This question-and-answer-based review will discuss the pharmacological and clinical differences between finerenone and other mineralocorticoid receptor antagonists and then move on to the main evidence in the cardiovascular and renal fields, closing, finally, on the potential role of therapeutic combination with sodium-glucose cotransporter 2 inhibitors (SGLT2is).

Spironolactone Induces Vasodilation by Endothelium-Dependent Mechanisms Involving NO and by Endothelium-Independent Mechanisms Blocking Ca2+ Channels

“…On the other hand, there are also non-steroidal MR compounds, which do not have gynecomastia as an adverse effect, with a high affinity (greater than spironolactone and eplerenone) for the mineralocorticoid receptor. One of these compounds is finerenone, which is associated with a lower risk of hyperkalemia, as evidenced by the results of phase I and phase II clinical trial programs [ 37 ]. Therefore, these data seem to show that replacing spironolactone with another drug that acts on these receptors, despite being less efficient and more expensive to produce, could be useful in preventing the risk of atherothrombotic and cardiovascular events.…”

Understanding the Clinical Relationship Between Diabetic Retinopathy, Nephropathy, and Neuropathy: A Comprehensive Review

“…Kidney scarring: Finerenone, a newer medication, may offer benefits in reducing tissue scarring in DN. It represents a promising intervention in managing the condition by potentially lowering the risk of kidney failure and cardiovascular complications [ 35 ].…”

Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease

“…It inhibits the binding of aldosterone and cortisol and reduces the recruitment of transcriptional cofactors in both the bound and not-bound conformational state of MR [ 57 ]. Differently from steroidal MRAs, finerenone has equal tissue distribution between the heart and the kidney, a shorter half-life, no active metabolites, higher MR selectivity than spironolactone, and higher receptor binding affinity than eplerenone [ 58 ].…”

“… The comparison between steroidal mineralocorticoid receptor antagonists (spironolactone and eplerenone) and finerenone [ 58 ]. Legend: MRA—mineralocorticoid receptor antagonist; MR—mineralocorticoid receptor; CNS—central nervous system.…”