Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Background: Data on the effect of mineralocorticoid receptor antagonist therapy on HbA _1c levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial.
Methods: In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally. Randomisation was performed with concealed allocation. The primary outcome of the trial was the composite of cardiovascular death and total (first and recurrent) heart failure events (ie, heart failure hospitalisation or urgent heart failure visit). In the present analysis, participants with diabetes at baseline (investigator-reported history of diabetes or baseline HbA _1c ≥6·5%) were excluded. New-onset diabetes was defined as a HbA _1c measurement of 6·5% or higher on two consecutive follow-up visits or new initiation of glucose-lowering therapy. The full-analysis set comprised all participants randomly assigned to study treatment, analysed according to their treatment assignment irrespective of the treatment received (ie, intention to treat). The safety analysis set comprised participants randomly assigned to study treatment who took at least one dose of the investigational product, analysed according to the treatment actually received. This trial is registered with ClinicalTrials.gov, NCT04435626, and is closed to new participants.
Findings: Between Sept 14, 2020, and Jan 10, 2023, 6001 participants were recruited and randomly assigned to finerenone or placebo. 3222 (53·7%) participants did not have diabetes at baseline and comprised the study population. During a median duration of follow-up of 31·3 months (IQR 21·5-36·3), 115 (7·2%) participants in the finerenone group and 147 (9·1%) in the placebo group developed new-onset diabetes, corresponding to a rate of 3·0 events per 100 person-years (95% CI 2·5-3·6) in the finerenone group and 3·9 events per 100 person-years (3·3-4·6) in the placebo group. Compared with placebo, finerenone significantly reduced the hazard of new-onset diabetes by 24% (hazard ratio [HR] 0·76 [95% CI 0·59-0·97], p=0·026). Fine-Gray competing risk analysis, accounting for the competing risk of death, yielded a similar finding (subdistribution HR 0·75 [0·59-0·96], p=0·024). Results were similar in sensitivity analyses, in which the definition of new-onset diabetes was expanded to include initiation of SGLT2 inhibitor treatment with diabetes as indication, restricted to HbA _1c measurements only, and restricted to new initiation of glucose-lowering drugs only (excluding SGLT2 inhibitor treatment). Findings were similar when participants treated with glucose-lowering drugs at baseline were excluded (n=15). The effect of finerenone, compared with placebo, on new-onset diabetes was consistent across key participant subgroups. Seven participants had an adverse event of new diabetes not captured by any of the definitions above.
Interpretation: In participants with heart failure with mildly reduced or preserved ejection fraction without diabetes, oral finerenone reduced the hazard of new-onset diabetes, representing a meaningful additional clinical benefit of this treatment in these individuals.
Funding: Bayer.
Competing Interests: Declaration of interests JHB reports advisory board honoraria from AstraZeneca and Bayer; consultant honoraria from Novartis and AstraZeneca; and travel grants from AstraZeneca. PSJ reports speakers' fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, and Sun Pharmaceuticals; advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices, and Roche; remuneration to employer for clinical trial work from AstraZeneca, Bayer, Novartis, and Novo Nordisk; and directorship at Global Clinical Trial Partners. BLC reports personal consulting fees from Alnylam, Bristol Myers Squibb, Cardior, Cardurion, Corvia, CVRx, Eli Lilly, Intellia, and Rocket; and participation on a data safety monitoring board for Novo Nordisk. ASD reports institutional research grants from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer; and personal consulting fees from Abbott, Alnylam, AstraZeneca, Bayer, Biofourmis, Boston Scientific, Medpace, Medtronic, Merck, Novartis, Parexel, Porter Health, Regeneron, River 2 Renal, Roche, Veristat, Verily, and Zydus. PV, PK, PS, and FA are employees of Bayer. CSPL reports research support from Novo Nordisk and Roche; consulting fees from Alleviant, Allysta, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia, Ionis, Janssen, Medscape, Merck, Novartis, Novo Nordisk, ProSciento, Quidel, Radcliffe Group, Recardio, Recor Medical, Roche, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and being a cofounder and non-executive director of Us2.ai. MS reports participation on advisory boards, consultancy, and honoraria for Novartis, Abbott, Merck, MSD, Vifor, AstraZeneca, Cardurion, Novo Nordisk, Bayer, and Boehringer Ingelheim. SJS reports research grants from the National Institutes of Health, the American Heart Association, AstraZeneca, Corvia, and Pfizer; and consulting fees from Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. AAV reports consultancy fees and research support to employer from Adrenomed, AnaCardio, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Corteria, Eli Lilly, Merck, Moderna, Novartis, Novo Nordisk, Roche, and SalubrisBio. FZ reports personal fees from 89bio, Abbott, Acceleron, Applied Therapeutics, Bayer, Betagenon, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, Cambrian, Cardior, Cereno, CellProthera, CEVA, Inventiva, KBP, Merck, Novo Nordisk, Owkin, Otsuka, Roche, NorthSea, and UsA2; stock options at G3 Pharmaceuticals; equities at Cereno, CardioRenal, and Eshmoun Clinical Research; and being the founder of Cardiovascular Clinical Trialists. BP reports consultancy for Bayer, AstraZeneca, Boehringer Ingelheim, Lexicon, Bristol Myers Squibb, KBP, Sarfez Pharmaceuticals, SQ Innovation, G3 Pharmaceuticals, SeaStar Medical, Vifor, ProIntel, and Brainstorm Medical; stock or stock options for KBP Biosciences, Sarfez Pharmaceuticals, SQ Innovation, Sea Star Medical, Vifor, ProIntel, and Brainstorm Medical; and patents US 9931412 (site specific delivery of eplerenone to the myocardium) and US pending 63/045,783 (histone modulating agents for the prevention and treatment of organ failure). MV reports research grant support from, participation on advisory boards for, or speaker engagements with American Regent, Amgen, AstraZeneca, Bayer, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche, Sanofi, and Tricog Health; and participation on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer, Occlutech, and Impulse Dynamics. SDS reports research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, the National Institutes of Health National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and Us2.ai; and consultancy for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, DiNAQOR, Tremeau, CellProthera, Moderna, American Regent, Sarepta, Lexicon, AnaCardio, Akros, and Valo. JVVM reports institutional payments, consultancy fees, and grants from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, Novartis, the British Heart Foundation, the National Institutes of Health National Heart, Lung, and Blood Institute, Boehringer Ingelheim, SQ Innovation, and Catalyze Group; personal consultancy fees from Alnylam, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, Bristol Myers Squibb, Cardurion, Cytokinetics, Ionis, Novartis, Regeneron, and River 2 Renal; personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, JB Chemicals & Pharmaceuticals, Lupin Pharmaceuticals, Medscape, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and the Translational Medicine Academy; participation on a data safety monitoring board for WIRB-Copernicus Group; and directorship of Global Clinical Trial Partners. ADH declares no competing interests.
(Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)