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. 2021 Oct 14;7(1):36-45.
doi: 10.1016/j.ekir.2021.10.008. eCollection 2022 Jan.

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

Peter Rossing  1   2 , Gerasimos Filippatos  3 , Rajiv Agarwal  4 , Stefan D Anker  5 , Bertram Pitt  6 , Luis M Ruilope  7   8   9 , Juliana C N Chan  10   11   12 , Adriaan Kooy  13   14   15 , Kieran McCafferty  16 , Guntram Schernthaner  17   18 , Christoph Wanner  19 , Amer Joseph  20 , Markus F Scheerer  21 , Charlie Scott  22 , George L Bakris  23 ; FIDELIO-DKD Investigators
Affiliations

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

Peter Rossing et al. Kidney Int Rep. .

Abstract

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 sodium-glucose 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 m2 receiving optimized renin-angiotensin 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.

Keywords: albuminuria; chronic kidney disease; finerenone; sodium-glucose cotransporter-2 inhibitors; type 2 diabetes.

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Figures

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Graphical abstract
Figure 1
Figure 1
Analysis of primary and secondary composite outcomes by baseline SGLT-2i use. CV, cardiovascular; SGLT-2i, sodium-glucose cotransporter-2 inhibitor.
Figure 2
Figure 2
Effect on albuminuria over time by baseline SGLT-2i use. Mixed-model analysis of UACR levels in patients who were (a) with or (b) without an SGLT-2i at baseline. Analysis included the following covariates: treatment group, stratification factors (region, albuminuria category at screening, eGFR category at screening), time, treatment over time, log-transformed baseline value nested within type of albuminuria at screening, and log-transformed baseline value over time. The change in UACR at month 4 was consistent irrespective of treatment with an SGLT-2i at baseline (Pinteraction = 0.31). eGFR, estimated glomerular filtration rate; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; LS, least-squares; UACR, urine albumin-to-creatinine ratio.
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