Anti-Oxidative Effect of Dapagliflozin, a Selective Sodium Glucose Transporter-2 Inhibitor, for Cardio-Renal Protection in Patients With Heart Failure With Reduced Ejection Fraction

Abstract

Background: Selective sodium glucose transporter-2 inhibitor (SGLT2i) has cardio-renal protective effects via osmotic diuresis and natriuresis, and other pleiotropic effects, such as anti-oxidative, anti-fibrotic, and anti-senescence effects, have been suggested. However, those pleiotropic effects have not yet been fully elucidated in a clinical study.

Methods: We investigated the effects of SGLT2i in patients with heart failure with reduced ejection fraction (HFrEF). Twenty-five HFrEF patients who were initially treated with dapagliflozin from 2021 to 2023 at Fukuoka University Hospital were enrolled and we investigated their baseline characteristics, medications, clinical laboratory examination findings, echocardiography findings, and additional pleiotropic serum markers before administration of dapagliflozin and 6 months later.

Results: The patients were 67.0 ± 13.6 years old, 64.0% were male, and their body mass index was 24.0 ± 4.5 kg/m². Only four patients (16.0%) had diabetes mellitus. With regard to medications, 64.0%, 76.0%, and 60.0% were already taking renin-angiotensin aldosterone system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, respectively, and these medications did not change significantly for 6 months. After treatment with dapagliflozin for 6 months, serum brain natriuretic peptide, left ventricular ejective function, hemoglobin, and urinary N-acetyl-β-D-glycosaminidase were significantly improved. In addition, high-sensitivity C-reactive protein and oxidative stress markers including myeloperoxidase, matrix metalloproteinase-1, and matrix metalloproteinase-9 significantly improved, while anti-fibrosis and anti-senescence markers did not.

Conclusions: Dapagliflozin had anti-oxidative effects in patients with HFrEF, in addition to cardio-renal protective effects. These anti-oxidative effects could be related to the cardio-renal protective effects of SGLT2i, even in a clinical setting.