Cardiovascular and Renal Benefit of Novel Non-steroidal Mineralocorticoid Antagonists in Patients with Diabetes.

Abstract

Novel non-steroidal mineralocorticoid receptor (MR) antagonists (MRAs) are a new class of drugs blocking adverse MR-mediated effects with an improved benefit-risk profile compared to steroidal MRAs. This review will provide information on the preclinical and clinical pharmacology of this new drug class and will discuss their future clinical applications in patients with cardiorenal disease. Non-steroidal MRAs such as esaxerenone, AZD9977, apararenone, ocedurenone (KBP-5074), and finerenone are newly approved or in clinical development for patients with cardiorenal disease including type 2 diabetes (T2D) and chronic kidney disease (CKD), hypertension -/+ CKD or heart failure. Unlike steroidal MRAs, non-steroidal MRAs do not induce sex hormone-related side effects and appear to mediate a lower risk of hyperkalemia while maintaining compelling clinical efficacy. Recently, new data from several clinical trials with non-steroidal MRAs have been published (e.g., FIDELIO-DKD, FIGARO-DKD, ESAX-DN, and BLOCK-CKD), and additional studies are currently underway (e.g., FINEARTS-HF and CLARION-CKD). These data and the clinical scientific basis for the ongoing studies will be discussed. Non-steroidal MRAs have been extensively explored in diabetic kidney disease. Selected candidates of this drug class reduced UACR in patients with varying degrees of CKD and T2D and have shown convincing cardiorenal protection, in particular finerenone. Furthermore, finerenone is currently tested in patients with heart failure with preserved ejection fraction.