medwireNews: The risk for new-onset type 2 diabetes may be significantly reduced in people with heart failure (HF) and a mildly reduced or preserved ejection fraction with use of the mineralocorticoid receptor antagonist finerenone, the FINEARTS-HF trial investigators say.
The incidence of diabetes was reduced by 24% for the participants randomly assigned to receive finerenone at an initial dose of 10–20 mg/day and a maximum maintenance dose of 20–40 mg/day, depending on baseline estimated glomerular filtration rate (eGFR), compared with those given placebo, report John McMurray (University of Glasgow, UK) and co-authors in The Lancet Diabetes & Endocrinology.
The study previously demonstrated that finerenone significantly reduced the composite endpoint of first or repeat worsening HF events and cardiovascular death in the full population of 6001 patients with New York Heart Association (NYHA) functional class II–IV disease and a left ventricular ejection fraction (LVEF) of at least 40%, as well as evidence of structural heart disease and a high N-terminal pro-B-type natriuretic peptide level.
The current prespecified analysis focused on the 3222 participants without diabetes at baseline who were followed up for a median of 31.3 months, and the authors describe the reduced risk for new-onset diabetes with finerenone as being “a meaningful additional clinical benefit.”
Overall, 7.2% of finerenone-treated patients developed new-onset diabetes, defined as a glycated hemoglobin level of 6.5% or above on two consecutive measurements or a new prescription for glucose-lowering therapy, compared with 9.1% of those given placebo.
This resulted in corresponding type 2 diabetes onset rates of 3.0 and 3.9 events per 100 person–years and a significant hazard ratio (HR) of 0.76 in favor of the mineralocorticoid receptor antagonist.
And this finding was confirmed by competing risk analysis accounting for the likelihood of death, and when the definition of new-onset diabetes was narrowed to include only glycated hemoglobin or only glucose-lowering drug use, or when excluding patients taking glucose-lowering drugs at baseline, the researchers say.
Of note, 61.4% of the patients had prediabetes at baseline and these patients were significantly more likely to develop new-onset diabetes during follow-up than those without (80.0 vs 59.8%).
Nevertheless, “[t]he effect of finerenone, compared with placebo, on new-onset diabetes was consistent across key participant subgroups,” the investigators report, including baseline normoglycemia or prediabetes, age, sex, race, BMI, smoking status, NYHA class, LVEF, eGFR, and medication use.
Finally, the researchers found that new-onset diabetes was associated with an elevated risk for cardiovascular death (HR=2.00), worsening HF events (rate ratio [RR]=1.84), the combination of these two factors (RR=1.88), and all-cause death (HR=1.55) after adjusting for a raft of confounding factors.
The authors of an accompanying comment write that the latest results “raise the possibility that the salutary effects on both cardiovascular outcomes and incident type 2 diabetes might all be mediated through the reduction of mineralocorticoid receptor activation.”
Hertzel Gerstein (McMaster University, Hamilton, Ontario, Canada) and Kamel Mohammedi (University of Bordeaux, France) suggest: “The fact that other aldosterone antagonists had either a harmful or neutral glucometabolic effect could be due to off-target effects on other steroid receptors or other mechanisms.”
They conclude that the study investigators “highlight the inter-relationship between heart failure and type 2 diabetes, and elegantly show a clear cardiovascular benefit of diabetes prevention.”
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