Efficacy and Safety of Finerenone in Patients with CKD and T2D by GLP-1RA Treatment

Introduction: Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that significantly reduced the risk of kidney and CV outcomes in patients with CKD and T2D in the FIDELIO-DKD trial. GLP-1RAs have also been shown to improve CV outcomes in patients with T2D as well as lowering albuminuria. The mechanism of action of finerenone and GLP-1RAs are largely independent but their combined effects are unknown. This analysis will report outcomes from the FIDELIO-DKD trial in patients by GLP-1RA treatment. Methods: FIDELIO-DKD (NCT02540993) randomized 5734 patients to oral finerenone or placebo. Patients with T2D, UACR 30-5000mg/g and eGFR 25-<75mL/min/1.73 m2, and treated with optimized RAS blockade, were included. The primary kidney outcome was time to kidney failure, sustained eGFR decline ≥40% from baseline, or renal death. Secondary outcomes included time to CV death, non-fatal MI, non-fatal stroke, or hospitalization for heart failure, and change in UACR from baseline to month 4. Results: Of the 5674 patients analyzed, 394 (6.9%) were treated with a GLP-1RA at baseline. Patients treated with GLP-1RAs at baseline had a higher BMI and A1C, with higher diuretic and statin use, lower median UACR and less presence of CVD than those who were not. There was no between-group interaction for the primary kidney (HR 1.17, 95% CI 0.71-1.90 with GLP-1RA; HR 0.80, 95% CI 0.71-0.91 without GLP-1RA; P-interaction 0.15) or secondary CV outcomes (HR 1.02, 95% CI 0.60-1.74 with GLP-1RA; HR 0.85, 95% CI 0.73-0.98 without GLP-1RA; P-interaction 0.51). The reduction in UACR was independent of GLP-1RA use (ratio of LS-means 0.63, 95% CI 0.56-0.70 with GLP-1RA; 0.69, 95% CI 0.67-0.72 without GLP-1RA; P-interaction 0.20). Overall, incidences of hyperkalemia events were similar in patients with and without GLP-1RA use. Conclusion: The effects of finerenone on kidney and CV outcomes appear consistent irrespective of GLP-1RA use, with a potential additive benefit for UACR reduction. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. A. Z. Lage: Employee; Self; Bayer Healthcare Pharmaceuticals Inc. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck & Co., Inc., Vascular Dynamics Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. A. Amod: Advisory Panel; Self; Aspen South Africa, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Servier Laboratories, Consultant; Self; Servier Laboratories, Other Relationship; Self; Bayer AG, Merck Sharp & Dohme Corp., Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Servier Laboratories. M. Marre: Board Member; Self; Merck Sharp & Dohme Corp., Consultant; Self; Novo Nordisk. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG