Finerenone according to insulin resistance in heart failure: Insights from the FINEARTS‐HF trial

Aims The estimated glucose disposal rate (eGDR) is a simple, non‐invasive measure of insulin resistance. In this exploratory analysis of FINEARTS‐HF, we evaluated whether lower eGDR, reflecting greater insulin resistance, is associated with adverse outcomes in heart failure (HF). Methods and results The eGDR was calculated at baseline using waist circumference, glycated haemoglobin, and hypertension status. Clinical outcomes and treatment effects of finerenone according to baseline eGDR (<median or ≥median) were evaluated. Among 5851 (98%) participants with a calculable eGDR (median [interquartile range] 5.1 [3.9–6.3] mg/kg/min), lower eGDR was associated with greater albuminuria and worse HF‐related health status at baseline. Compared with participants with eGDR ≥5.1 mg/kg/min, those with eGDR <5.1 mg/kg/min experienced a 63% higher rate of cardiovascular death and total HF events (adjusted rate ratio [aRR] 1.63; 95% confidence interval [CI] 1.41–1.87; p < 0.001). Similar findings were observed in participants with diabetes (aRR 1.72; 95% CI 1.40–2.12) and without diabetes (aRR 1.34; 95% CI 1.07–1.68; p interaction = 0.06). Lower baseline eGDR was additionally associated with a higher rate of vascular events, kidney outcomes, new‐onset diabetes, and all‐cause death. Treatment benefits of finerenone on cardiovascular death and total HF events ( p interaction = 0.64) and new‐onset diabetes ( p interaction = 0.36) appeared consistent irrespective of baseline eGDR category. Baseline eGDR category did not modify the safety profile of finerenone. Conclusions The eGDR, a validated measure of insulin resistance, was associated with a wide range of cardiovascular, kidney, and metabolic outcomes in patients with HF, including among those without diabetes. Finerenone reduced risk of cardiovascular outcomes and new‐onset diabetes, irrespective of baseline insulin resistance. Clinical Trial Registration: ClinicalTrials.gov NCT04435626.