Finerenone in Patients with CKD and T2D by SGLT-2i Treatment: An Analysis of the FIDELIO-DKD Study

Abstract

IntroductionThe selective, nonsteroidal mineralocorticoid receptor antagonist finerenone was investigated in FIDELIO-DKD in patients with CKD and T2D (NCT02540993). Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are recommended for CKD in T2D to reduce risk of CKD progression. We report a predefined exploratory analysis of patients by SGLT-2i use. MethodsPatients (N=5674) with T2D, urine albumin-to-creatinine ratio (UACR) 30–5000 mg/g and estimated glomerular filtration rate (eGFR) 25–<75 mL/min/1.73 m2 receiving optimized RAS blockade were randomized to finerenone (10 mg daily increasing to 20 mg daily) or placebo. ResultsOf 5674 patients, 259 (4.6%) received SGLT-2i at baseline. Overall, finerenone significantly reduced the primary (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) vs placebo (p=0.001 and p=0.03, respectively) with no effect on A1C. Results were consistent irrespective of SGLT-2i use at baseline for the primary and key secondary CV outcomes (interaction p-value 0.21 and 0.46, respectively). Reduction in UACR with finerenone was seen without SGLT-2i use (ratio of LS-means 0.68, 0.65–0.71; p<0.0001) and on top of SGLT-2is at baseline (ratio of LS-means 0.75, 0.62–0.90; p=0.0024). Treatment-emergent hyperkalemia events were fewer with SGLT-2i vs no SGLT-2i (post hoc analysis). ConclusionThe benefits of finerenone on kidney and CV outcomes in patients with CKD and T2D appear consistent in the absence or presence of SGLT2i, with UACR improvement observed in patients already receiving SGLT-2i at baseline.