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.