Assessing the safety and efficacy of finerenone in patients with chronic kidney disease (CKD) and comorbid type II diabetes (T2D), a systematic review

Suwanee, GA

Introduction: Potassium-sparing diuretics have long since held an important place in clinical practice; though, there are only a handful of options available. A novel potassium sparing diuretic, finerenone, has recently been investigated in patients with CKD with concomitant T2D to determine its safety and efficacy in a larger group of patients.

Objectives: The purpose of this abstract is to identify and analyze phase III trial data of novel diuretic therapies in patients with CKD and comorbid T2D.

Methods: The terms, “chronic kidney disease”, “type 2 diabetes”, “new therapy”, “effect”, “renal function”, and “cardiovascular disease”, were utilized to conduct a systematic literature search using Cochrane, PubMed, and EMBASE. Two trials were found (FIDELIO-DKD and FIGARO-DKD), reviewed, and evaluated.

Results: In the FIDELIO-DKD and FIGARO-DKD trials, patients were given either finerenone (a novel potassium-sparing diuretic) or placebo in a 1:1 fashion to help establish its safety and efficacy in preventing renal and cardiovascular events in patients with T2D and CKD. Baseline characteristics in FIDELIO-DKD were average age of 64 years, 70.2% male, 63.3% Caucasian, 16.6-year average history of diabetes, average Hemoglobin A1C (HbA1C) of 7.7%, 52.5% eGFR of 25 to <45ml/min/1.73m2, and 65.7% receiving angiotensin-receptor blocker therapy. At a 2.6-year median follow-up, 504 of 2,833 patients completing treatment experienced a primary event of either death by renal cause, sustained decrease of eGFR by 40% from baseline, or kidney failure in the finerenone group as compared to 600 of 2,841 in the placebo group (Hazard Ratio 0.82; 95% Confidence Interval (CI), 0.73-0.93; p=0.001). In addition, 367 and 420 (finerenone and placebo groups, respectively) experienced a secondary event of death from cardiovascular causes, nonfatal myocardial infarction (MI), heart failure (HF) resulting in hospitalization, or nonfatal stroke (Hazard Ratio, 0.86; 95% CI, 0.75-0.99; p=0.03).

In FIGARO-DKD, baseline characteristics included an average age of 64 years, 71.8% male, 71.8% Caucasian, average HbA1C of 7.7%, 61.7% eGFR ≥60 ml/min/1.73m2, and 99.9% receiving some form of renin-angiotensin system inhibitor. The primary outcomes measured were a composite of death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for HF. At a 3.4-year follow-up, data showed a decrease in hospitalization for HF in the finerenone group as compared to the placebo group (Hazard Ratio, 0.71; 95% CI, 0.56-0.90). Both FIDELIO-DKD and FIGARO trials used a time-to-event analysis approach to measure primary and secondary outcomes. Notably, SGLT2 inhibitors were underutilized in both trials; thus, the efficacy of finerenone in the cohort of patients receiving SGLT2 inhibitors remains unknown.

Conclusion: Finerenone has recently been FDA approved and is currently being marketed under the brand name Kerendia. It has demonstrated its benefit in reducing kidney function decline, kidney failure, hospitalization for heart failure, and non-fatal MI in patients with T2D and comorbid CKD. However, it remains unclear what its definitive place in therapy is and should warrant further research.