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Randomized Controlled Trial
. 2023 Feb;25(2):407-416.
doi: 10.1111/dom.14883. Epub 2022 Nov 2.

Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use

Peter Rossing  1   2 , Rajiv Agarwal  3 , Stefan D Anker  4 , Gerasimos Filippatos  5 , Bertram Pitt  6 , Luis M Ruilope  7   8   9 , Vivian Fonseca  10 , Guillermo E Umpierrez  11 , Maria Luiza Caramori  12 , Amer Joseph  13 , Marc Lambelet  14 , Robert Lawatscheck  15 , George L Bakris  16 ; FIDELIO-DKD and FIGARO-DKD Investigators
Affiliations
Randomized Controlled Trial

Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use

Peter Rossing et al. Diabetes Obes Metab. 2023 Feb.

Abstract

Aims: To explore the modifying effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on outcomes with finerenone across a wide spectrum of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the pooled analysis of FIDELIO-DKD and FIGARO-DKD.

Materials and methods: Patients with T2D and CKD treated with optimized renin-angiotensin system blockade were randomized to finerenone or placebo. Effects of finerenone on a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite outcome (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decline, or renal death), change in urine albumin-to-creatinine ratio (UACR), and safety were analysed by GLP-1RA use.

Results: Of 13 026 patients, 944 (7.2%) used GLP-1RAs at baseline. Finerenone reduced the risk of the cardiovascular composite outcome (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.52-1.11 with GLP-1RA; HR 0.87, 95% CI 0.79-0.96 without GLP-1RA; P-interaction = 0.63) and the kidney composite outcome (HR 0.82, 95% CI 0.45-1.48 with GLP-1RA; HR 0.77, 95% CI 0.67-0.89 without GLP-1RA; P-interaction = 0.79) irrespective of baseline GLP-1RA use. Reduction in UACR with finerenone at Month 4 was -38% in patients with baseline GLP-1RA use compared with -31% in those without GLP-1RA use (P-interaction = 0.03). Overall safety and incidence of hyperkalaemia were similar, irrespective of GLP-1RA use.

Conclusions: The cardiorenal benefits of finerenone on composite cardiovascular and kidney outcomes and UACR reduction in patients with CKD and T2D appear to be maintained, regardless of GLP-1RA use. Subsequent studies are needed to investigate any potential benefit of this combination.

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Conflict of interest statement

Peter Rossing reports personal fees from Bayer during the conduct of the study, and has received research support and personal fees from AstraZeneca and Novo Nordisk, and personal fees from Astellas Pharma Inc., Boehringer Ingelheim, Eli Lilly and Company, Gilead, Merck, Merck Sharp & Dohme, Mundipharma, Sanofi, and Vifor Pharma. All fees are given to Steno Diabetes Center Copenhagen. Rajiv Agarwal reports personal fees and nonfinancial support from Bayer Healthcare Pharmaceuticals Inc. during the conduct of the study, personal fees and nonfinancial support from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fresenius, Janssen, Relypsa, Sanofi, and Vifor Pharma, personal fees from Ironwood Pharmaceuticals, Lexicon, Merck & Co., and Reata, and nonfinancial support from E. R. Squibb & Sons, Opko Pharmaceuticals, and Otsuka America Pharmaceutical. He is also a member of data safety monitoring committees for Amgen, AstraZeneca, and Celgene, steering committees of randomized trials for Akebia Therapeutics, Bayer, Janssen, and Relypsa, adjudication committees for AbbVie, Bayer, Boehringer Ingelheim, and Janssen, has served as an associate editor of the American Journal of Nephrology and Nephrology Dialysis and Transplantation and has been an author for UpToDate, and has received research grants from the US Veterans Administration and the National Institutes of Health. Stefan D. Anker has received research support from Abbott Vascular and Vifor Pharma, and personal fees from Abbott Vascular, Bayer, Boehringer Ingelheim, BRAHMS, Cardiac Dimensions, Impulse Dynamics, Novartis, Servier, and Vifor Pharma. Gerasimos Filippatos reports lectures fees and/or that he is a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor Pharma. He is a senior consulting editor for JACC Heart Failure, and has received research support from the European Union.

Bertram Pitt reports consultant fees for Ardelyx, AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, PhaseBio, Sanofi/Lexicon, Sarfez Pharmaceuticals, scPharmaceuticals, SQ Innovation, Tricida, and Vifor Pharma/Relypsa Inc., has stock options for Ardelyx, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Sarfez Pharmaceutical Inc., scPharmaceuticals, SQ Innovation, Tricida, and Vifor Pharma/Relypsa Inc., and holds 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 63/045784). Luis M. Ruilope has received consultancy fees from Bayer. Vivian Fonseca has served as a paid consultant for Abbott, Asahi, AstraZeneca, Bayer, Novo Nordisk, and Sanofi, and has patent and ownership interests in BRAVO4Health. Guillermo E. Umpierrez has received research support (to Emory University) from AstraZeneca, Bayer, and Dexcom Inc. Maria Luiza Caramori reports grants and personal fees from Bayer, personal fees from AstraZeneca and Boehringer‐Ingelheim and grants from Novartis. Grants are paid to her institution. Amer Joseph was a full‐time employee of Bayer AG, Division Pharmaceuticals, Germany, at the time of the studies and analysis, and is now a full‐time employee of Chiesi Farmaceuitici S.p.A, Parma, Italy. Marc Lambelet is an external employee of Bayer AG. Robert Lawatscheck is a full‐time employee of Bayer AG, Division Pharmaceuticals, Germany. George L. Bakris reports research funding, paid to the University of Chicago Medicine, from Bayer, during the conduct of the study, and research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics, has acted as a consultant for and received personal fees from Alnylam, Merck, and Relypsa, Inc., and is an editor of the American Journal of Nephrology, Nephrology, and Hypertension, a section editor of UpToDate, and an associate editor of Diabetes Care and Hypertension Research.

Figures

FIGURE 1
FIGURE 1
Analysis of efficacy outcomes in patients receiving/not receiving a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA). The cardiovascular composite outcome included time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The kidney composite outcome included time to kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline from baseline, or renal death. CI, confidence interval; PY, patient‐years
FIGURE 2
FIGURE 2
Change in urine albumin‐to‐creatinine ratio over time in patients receiving/not receiving a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) at baseline. P‐interaction at 4 months derived from analysis of covariance = 0.0305. Mixed model with factors treatment group, region, estimated glomerular filtration rate category at screening, type of albuminuria at screening, time, treatment*time, study, study*treatment, log‐transformed baseline value nested within type of albuminuria at screening, and log‐transformed baseline value*time as covariate. CI, confidence interval; LS, least squares
FIGURE 3
FIGURE 3
Efficacy outcomes considering the effect of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use at any time on‐treatment. The cardiovascular composite outcome included time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The kidney composite outcome included time to kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline from baseline, or renal death. *Interaction P‐value for adjusted hazard ratio is based on a two‐sided Wald test. CI, confidence interval
FIGURE 4
FIGURE 4
Forest plot of analysis of covariance for ratio to baseline at Month 4 of urine albumin‐to‐creatinine ratio (UACR) by glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) and sodium‐glucose cotransporter‐2 (SGLT2) inhibitor use at baseline (full analysis set). Per subgroup category an ANCOVA with factors treatment group, region, eGFR category at screening, type of albuminuria at screening, cardiovascular disease history, study, log‐transformed baseline value nested within type of albuminuria and the interaction between study and treatment was applied. For Month 4, the closest observation to Day 120 within a time window of 120 ± 30 days after randomization was used. Patients with no measurements within this time window were excluded from the analysis. *Geometric mean of the ratio of UACR at Month 4 to baseline. CI, confidence interval; LS, least squares
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References

    1. United States Renal Data System . Chapter 1: Incidence, prevalence, patient characteristics, and treatment modalities. USRDS Annual Data Report Volume 2: ESRD in the United States, 2020.
    1. United States Renal Data System . Chapter 11: International comparisons. USRDS Annual Data Report Volume 2: ESRD in the United States, 2020.
    1. International Diabetes Federation . IDF Diabetes Atlas. 10th ed. Brussels: International Diabetes Federation; 2021.
    1. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302‐308. - PMC - PubMed
    1. Wu B, Bell K, Stanford A, et al. Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns‐NHANES 2007‐2012. BMJ Open Diabetes Res Care. 2016;4(1):e000154. - PMC - PubMed

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