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

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  • FIDELIO-DKD Investigators

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 chronic kidney disease (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 (Pinteraction = 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 (Pinteraction = 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.

OriginalsprogEngelsk
TidsskriftKidney International Reports
Vol/bind7
Udgave nummer1
Sider (fra-til)36-45
ISSN2468-0249
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
PR reports receiving personal fees from Bayer during the conduct of the study; research support and personal fees from AstraZeneca and Novo Nordisk; and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi, and Vifor. All fees are given to Steno Diabetes Center Copenhagen. GF reports receiving lecture fees and/or serving as a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor; being a Senior Consulting Editor for JACC Heart Failure; and receiving research support from the European Union. RA reports receiving personal fees and nonfinancial support from Bayer Healthcare Pharmaceuticals Inc. during the conduct of the study; receiving personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius, Janssen, Relypsa, Sanofi, and Vifor Pharma; receiving personal fees from Ironwood Pharmaceuticals, Lexicon, Merck & Co., and Reata; receiving nonfinancial support from E. R. Squibb & Sons, OPKO Pharmaceuticals, and Otsuka America Pharmaceutical; serving as a member of data safety monitoring committees for Amgen, AstraZeneca, and Celgene; serving as a member of steering committees of randomized trials for Akebia Therapeutics, Bayer, Janssen, and Relypsa; serving as a member of adjudication committees for AbbVie, Bayer, Boehringer Ingelheim, and Janssen; serving as associate editor for the American Journal of Nephrology and Nephrology Dialysis and Transplantation and an author for UpToDate; and receiving research grants from the US Veterans Administration and the National Institutes of Health. SDA reports receiving research support from Abbott Vascular and Vifor International and personal fees from Abbott Vascular, Bayer, Boehringer Ingelheim, BRAHMS, Cardiac Dimensions, Impulse Dynamics, Novartis, Servier, and Vifor International. BP reports receiving consultant fees from Ardelyx, AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, PhaseBio, Sanofi/Lexicon, Sarfez, scPharmaceuticals, SQ Innovation, Tricida, and Vifor/Relypsa; having stock options for Ardelyx, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Sarfez, scPharmaceuticals, SQ Innovation, Tricida, and Vifor/Relypsa; and having a patent for site-specific delivery of eplerenone to the myocardium (US patent #9931412) and a provisional patent for histone acetylation-modulating agents for the treatment and prevention of organ injury (provisional patent US 63/045,784). LMR reports receiving consultancy fees from Bayer. JCNC reports receiving grants and/or honoraria for consultancy or giving lectures from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Hua Medicine, Lee Powder, Merck Serono, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Sanofi, and Servier. AK reports receiving research funding paid to the Bethesda Diabetes Research Center Netherlands, from AstraZeneca, Merck Sharpe & Dohme, Novo Nordisk, and Sanofi Aventis. KM reports receiving research funding from AstraZeneca and consultancy/speaker honoraria from AstraZeneca, Bayer, Napp, Oncacare, Pharmacosmos, and Vifor Fresenius. GS reports receiving honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Mundipharma, and Takeda. CW reports receiving advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, MSD, and Mundipharma. AJ and MFS report being full-time employees of Bayer AG, Germany. MFS is also a shareholder in AstraZeneca, Bayer, Eli Lilly, and Novo Nordisk. CS reports being a full-time employee of Bayer PLC, United Kingdom. GLB reports receiving research funding, paid to the University of Chicago Medicine, from Bayer during the conduct of the study; receiving research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; acting as a consultant and received personal fees from for Alnylam, Merck, and Relypsa; serving as an editor for the American Journal of Nephrology, Nephrology, and Hypertension, and Section Editor for UpToDate; and serving as an associate editor for Diabetes Care and Hypertension Research.

Funding Information:
The authors are indebted to the patients who have participated in this trial, the FIDELIO-DKD trial investigators, and the study centers that supported the trial. The FIDELIO-DKD study and subanalyses were funded by Bayer AG . Medical writing assistance was provided by Kate Weatherall, PhD, on behalf of Chameleon Communications International, and was funded by Bayer AG.

Publisher Copyright:
© 2021 International Society of Nephrology

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