The non-steroidal mineralocorticoid receptor antagonist finerenone is a novel therapeutic option for patients with Type 2 diabetes and chronic kidney disease

Abstract

Despite strong preclinical data supporting the use of mineralocorticoid receptor antagonists (MRAs) to provide cardiorenal protection in rodent models of diabetes, the clinical evidence of their utility in treating chronic kidney disease (CKD) has been limited. Two major clinical trials (FIDELIO-DKD and FIGARO-DKD) including more than 13,000 patients with albuminuric CKD and Type 2 diabetes randomized to placebo or finerenone (MRA) have recently provided exciting results showing a significant risk reduction for kidney and cardiovascular outcomes. In this review, we will summarize the major findings of these trials, together with post-hoc and pooled analyses that have allowed evaluation of the efficacy and safety of finerenone across the spectrum of CKD, revealing significant protective effects of finerenone against kidney failure, new-onset atrial fibrillation or flutter, new-onset heart failure, cardiovascular death, and first and total heart-failure hospitalizations. Moreover, we will discuss the current evidence that supports the combined use of MRAs with sodium-glucose co-transporter-2 inhibitors, either by providing an additive cardiorenal benefit or by decreasing the risk of hyperkalemia. Although the mechanisms of protection by finerenone have only been partially explored in patients, rodent studies have shed light on its anti-inflammatory and anti-fibrotic effects in models of kidney disease, which is one of the main drivers for testing the efficacy of finerenone in non-diabetic CKD patients in the ongoing FIND-CKD trial.

Finerenone cardiorenal effects and its placement in treatment of chronic kidney disease in patients with type 2 diabetes mellitus: A review

“…Таким образом, суммарно во всех исследованиях финеренона III фазы удалось продемонстрировать надежные доказательства высокой эффективности препарата в сниже-нии кардиоваскулярного и почечного риска у больных СД 2 с ХБП I-IV стадий, независимо от наличия исходного ССЗ. Важно, что в условиях двойной блокады -РАС и МКР -выявлено незначительное количество нежелательных явлений и отмечен хороший профиль безопасности [31].…”

Finerenone: Efficacy of a New Nonsteroidal Mineralocorticoid Receptor Antagonist in Treatment of Patients With Chronic Kidney Disease and Type 2 Diabetes

“…A posthoc analysis of the CREDENCE trial showed that canagliflozin reduced the risk of hyperkalemia among patients with CKD and T2DM who are on RAAS inhibitor treatment. 14…”

“…Results from this particular trial is expected to become available in 2025. 14 The FIONA trial undertakes the safety and efficacy of finerenone in a pediatric population. This study will randomize children and adolescents with CKD with severely elevated proteinuria to finereone or placebo in addition to the standard of care (ACE-i or ARB).…”

“…The goal is to evaluate the potential to reduce proteinuria in 6 months. 14 The CONFIDENCE phase II trial is also underway that will investigate if combined MRA and SGLT2 therapy is superior to either medication used alone. This study will investigate if there is any benefit from combining empagliflozin and finerenone in patients with T2DM and CKD.…”

“…Patients will be randomized to finerenone alone, empagliflozin alone and a combination group and the primary outcome (UACR reduction from baseline in the empagliflozin vs combination) will be assessed after 3 months of treatment. 14…”