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Randomized Controlled Trial
. 2022 Jan;24(1):125-134.
doi: 10.1111/dom.14558. Epub 2021 Oct 11.

Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP-1RA treatment: A subgroup analysis from the FIDELIO-DKD trial

Peter Rossing  1   2 , Rajiv Agarwal  3 , Stefan D Anker  4 , Gerasimos Filippatos  5 , Bertram Pitt  6 , Luis M Ruilope  7   8   9 , Aslam Amod  10 , Michel Marre  11 , Amer Joseph  12 , Andrea Lage  13 , Charlie Scott  14 , George L Bakris  15 ; FIDELIO-DKD Investigators
Affiliations
Randomized Controlled Trial

Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP-1RA treatment: A subgroup analysis from the FIDELIO-DKD trial

Peter Rossing et al. Diabetes Obes Metab. 2022 Jan.

Abstract

Aims: Finerenone significantly reduced the risk of kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease and type 2 diabetes in the FIDELIO-DKD trial (NCT02540993). This exploratory subgroup analysis investigates the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on the treatment effect of finerenone.

Materials and methods: Patients with type 2 diabetes, urine albumin-to-creatinine ratio (UACR) 30-5000 mg/g and estimated glomerular filtration rate 25-<75 ml/min per 1.73 m2 receiving optimized renin-angiotensin system blockade were randomized to finerenone or placebo.

Results: Of the 5674 patients analysed, overall, 394 (6.9%) received GLP-1RAs at baseline. A reduction in UACR with finerenone was observed with or without baseline GLP-1RA use; ratio of least-squares means 0.63 (95% confidence interval 0.56, 0.70) with GLP-1RA use and 0.69 (95% confidence interval 0.67, 0.72) without GLP-1RA use (p value for interaction .20). Finerenone also significantly reduced the primary kidney (time to kidney failure, sustained decrease in estimated glomerular filtration rate ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) versus placebo, with no clear difference because of GLP-1RA use at baseline (p value for interaction .15 and .51 respectively) or any time during the trial. The safety profile of finerenone was similar between subgroups.

Conclusions: This exploratory subgroup analysis suggests that finerenone reduces UACR in patients with or without GLP-1RA use at baseline, and the effects on kidney and CV outcomes are consistent irrespective of GLP-1RA use.

Keywords: chronic kidney disease; finerenone; glucagon-like peptide-1 receptor agonist; mineralocorticoid receptor antagonist; type 2 diabetes.

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Conflict of interest statement

PR reports personal fees from Bayer, during the conduct of the study; he has received research support and personal fees from AstraZeneca and Novo Nordisk, and personal fees from Eli Lilly and Company, Boehringer Ingelheim, Astellas Pharma Inc., Gilead, Merck, Merck Sharp and Dohme, Mundipharma, Sanofi and Vifor Pharma. All fees are given to Steno Diabetes Center Copenhagen. RA reports personal fees and non‐financial support from Bayer Healthcare Pharmaceuticals Inc., during the conduct of the study; he also reports personal fees and non‐financial support from Akebia Therapeutics, Janssen, Relypsa Inc., Vifor Pharma, Boehringer Ingelheim, Sanofi, Eli Lilly and Company, AstraZeneca and Fresenius; he has received personal fees from Ironwood Pharmaceuticals, Merck & Co., Lexicon and Reata Pharmaceuticals, and non‐financial support from Otsuka America Pharmaceutical Inc., OPKO Health, Inc. and E. R. Squibb & Sons; he is a member of data safety monitoring committees for Amgen, AstraZeneca, and Celgene; a member of steering committees of randomized trials for Akebia Therapeutics, Bayer, Janssen and Relypsa Inc.; a member of adjudication committees for AbbVie, Bayer, Boehringer Ingelheim and Janssen; he has served as associate editor of the American Journal of Nephrology and Nephrology Dialysis and Transplantation and has been an author for UpToDate; and he has received research grants from the US Veterans Administration and the National Institutes of Health. SDA has received research support from Abbott Vascular and Vifor Pharma, and personal fees from Abbott Vascular, Boehringer Ingelheim, Bayer, BRAHMS, Novartis, Servier, Vifor Pharma, Impulse Dynamics and Cardiac Dimensions. GF reports lectures fees and/or that he is a committee member of trials and registries sponsored by Bayer, Novartis, Vifor Pharma, Medtronic, Servier, Amgen and Boehringer Ingelheim. He is a senior consulting editor for JACC Heart Failure, and he has received research support from the European Union. BP reports consultant fees for Bayer, AstraZeneca, Sanofi/Lexicon, scPharmaceuticals, SQ Innovation, G3 Pharmaceuticals, Sarfez Pharmaceutical, Inc., PhaseBio, Vifor Pharma/Relypsa, Inc., Cereno Scientific, Ardelyx, KBP Biosciences, Boehringer Ingelheim, Brainstorm Medical and Tricida; he has stock options for Ardelyx, KBP Biosciences, SQ Innovation, Sarfez Pharmaceutical, Inc., scPharmaceuticals, Cereno Scientific G3 Pharmaceuticals, Vifor Pharma/Relypsa, Inc., Brainstorm Medical and Tricida; he also holds a patent for site‐specific delivery of eplerenone to the myocardium (US patent no. 9931412) and a provisional patent for histone‐acetylation‐modulating agents for the treatment and prevention of organ injury (provisional patent US 63/045784). LMR has no disclosures. AA has served on advisory boards or consulted for Aspen Pharmacare, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck SA, Novo Nordisk and Servier. MM is a consultant for the Novo Nordisk Algerian subsidiary and has received personal fees from Bayer AG, Novo Nordisk, Merck, Sharp and Dohme and Servier during the past 3 years. AJ is a full‐time employee of Bayer AG, Division Pharmaceuticals, Germany. AL is a full‐time employee of Bayer SA, Division Pharmaceuticals, Brazil. CS is a full‐time employee of Bayer PLC, Division Pharmaceuticals, United Kingdom. GLB reports research funding, paid to the University of Chicago Medicine, from Bayer, during the conduct of the study; he also reports research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; he acted as a consultant and received personal fees from for Merck, Relypsa, Inc. and Alnylam; he is an editor of American Journal of Nephrology, Nephrology and Hypertension, and section editor of UpToDate; and he is an associate editor of both Diabetes Care and Hypertension Research.

Figures

FIGURE 1
FIGURE 1
Effect on albuminuria over time by baseline GLP‐1RA use. Mixed model analysis of UACR levels in patients, A, with or, B, without GLP‐1RA at baseline. Analysis included the following covariates: treatment group, stratification factors (region, albuminuria category at screening and 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. eGFR, estimated glomerular filtration rate; GLP‐1RA, glucagon‐like peptide‐1 receptor agonist; LS, least‐squares; Ref, reference; UACR, urine albumin‐to‐creatinine ratio
FIGURE 2
FIGURE 2
Primary and secondary composite outcomes by baseline GLP‐1RA use. †HR (95% CI) values based on the stratified Cox proportional hazards model estimated within each level of the subgroup variable. ‡ p value (two‐sided) for the interaction of treatment group and each baseline subgroup based on the Cox proportional hazards model, including the terms treatment group, baseline subgroup and their interaction. CI, confidence interval; CV, cardiovascular; GLP‐1RA, glucagon‐like peptide‐1 receptor agonist; HR, hazard ratio; PY, patient‐years
See this image and copyright information in PMC

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