Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy

Introduction: FIDELIO-DKD (Finerenone in reducing kiDnEy faiLure and disease prOgression in Diabetic Kidney Disease) investigated the nonsteroidal, selective mineralocorticoid receptor (MR) antagonist finerenone in patients with CKD and type 2 diabetes (T2D). This analysis explores the impact of use of sodiumglucose cotransporter-2 inhibitor (SGLT-2i) on the treatment effect of finerenone. Methods: Patients (N = 5674) with T2D, urine albumin-to-creatinine ratio (UACR) of 30 to 5000 mg/g and estimated glomerular filtration rate (eGFR) of 25 to <75 ml/min per 1.73 m(2) receiving optimized reninangiotensin system (RAS) blockade were randomized to finerenone or placebo. Endpoints were change in UACR and a composite kidney outcome (time to kidney failure, sustained decrease in eGFR >= 40% from baseline, or renal death) and key secondary cardiovascular outcomes (time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) (ClinicalTrials.gov, NCT02540993). Results: Of 5674 patients, 259 (4.6%) received an SGLT-2i at baseline. Reduction in UACR with finerenone was found with or without use of SGLT-2i at baseline, with ratio of least-squares means of 0.69 (95% CI = 0.66-0.71) and 0.75 (95% CI -= 0.62-0.90), respectively (P-interaction = 0.31). Finerenone also significantly reduced the kidney and key secondary cardiovascular outcomes versus placebo; there was no clear difference in the results by SGLT-2i use at baseline (P-interaction = 0.21 and 0.46, respectively) or at any time during the trial. Safety was balanced with or without SGLT-2i use at baseline, with fewer hyperkalemia events with finerenone in the SGLT-2i group (8.1% vs. 18.7% without). Conclusion: UACR improvement was observed with finerenone in patients with CKD and T2D already receiving SGLT-2is at baseline, and benefits on kidney and cardiovascular outcomes appear consistent irrespective of use of SGLT-2i.

Automated summary

The FIDELIO-DKD study investigated the treatment effect of finerenone in patients with CKD and T2D, showing that finerenone can improve UACR and have beneficial effects on kidney and cardiovascular outcomes, regardless of whether patients were also using SGLT-2i.