Efficacy and Safety of Finerenone in Patients with CKD and T2D by GLP-1RA Treatment

Abstract

IntroductionFinerenone is a nonsteroidal mineralocorticoid receptor antagonist that significantly reduces risk of kidney and CV outcomes in patients with CKD and T2D. GLP-1RAs have also been shown to improve CV outcomes in patients with T2D. Mechanisms of action of finerenone and GLP-1RAs are largely independent but their combined effects are unknown. We report outcomes from the FIDELIO-DKD trial in patients by GLP-1RA treatment. MethodsFIDELIO-DKD (NCT02540993) randomized 5734 patients with T2D (UACR 30–5000mg/g; eGFR 25–<75mL/min/1.73 m2; treated with optimized RAS blockade) to finerenone or placebo. Primary outcome was time to kidney failure, sustained eGFR decline ≥40% from baseline, or renal death. Secondary outcomes included time to CV death, non-fatal MI, non-fatal stroke, or hospitalization for heart failure, and change in UACR from baseline to month 4. ResultsOf 5674 patients analyzed, 394 (6.9%) were treated with a GLP-1RA at baseline. There was no between-group interaction for primary kidney (HR 1.17, 95%CI 0.71–1.90 with GLP-1RA; HR 0.80, 95%CI 0.71–0.91 without GLP-1RA; P-interaction 0.15) or secondary CV outcomes (HR 1.02, 95%CI 0.60–1.74 with GLP-1RA; HR 0.85, 95%CI 0.73–0.98 without GLP-1RA; P-interaction 0.51). Reduction in UACR was independent of GLP-1RA use (ratio of LS-means 0.63, 95%CI 0.56–0.70 with GLP-1RA; 0.69, 95%CI 0.67–0.72 without GLP-1RA; P-interaction 0.20). Incidences of hyperkalemia events were similar in patients with and without GLP-1RA use. ConclusionEffects of finerenone on kidney and CV outcomes appear consistent irrespective of GLP-1RA use, with a potential additive benefit for UACR reduction.