Nassif ME, Windsor S, Tang F, et al. - In an investigator-initiated, multi-center, randomized controlled trial—DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction)—researchers investigated the impacts of sodium-glucose co-transporter-2 inhibitors in patients with established heart failure (HF) with reduced ejection fraction, including those with and without type 2 diabetes mellitus. Participants had left ventricular ejection fraction ≤ 40%, New York Heart Association class II-III, estimated glomerular filtration rate ≥ 30 mL/min/1.73m², and elevated natriuretic peptides. The participants were 263 in total and were randomly given dapagliflozin 10 mg daily or placebo for 12 weeks. No change was seen in mean N-terminal pro b-type natriuretic peptide but the proportion of patients showing clinically meaningful improvements in HF-associated health status or natriuretic peptides was increased when dapagliflozin was given for 12 weeks to treat patients with HF and reduced ejection fraction. The extension of dapagliflozin's benefits, on clinically meaningful HF measures, to patients without type 2 diabetes mellitus was indicated.