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Mechanisms and Therapeutic Potential of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure

Huang Z, Ling G, Fang C, Wu Z, Ye S, Zhang C, Luo C, Zheng B

Reviews in cardiovascular medicine, 2026

Abstract

Heart failure (HF) is a major global cause of hospitalization and mortality, representing a complex clinical syndrome with significant unmet therapeutic needs. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), originally developed for glycemic control, have recently demonstrated remarkable efficacy in the management of HF. This review comprehensively examines the mechanisms of action and therapeutic potential of SGLT2is in HF, with a focus on their multifaceted effects on hemodynamics, cardiac metabolism, inflammatory responses, oxidative stress, and neuroendocrine activation. In addition, clinical trial outcomes and safety profiles of SGLT2is in HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mid-range ejection fraction (HFmrEF) are thoroughly evaluated. Finally, this article discusses future research directions and clinical application prospects, aiming to provide novel insights and strategies for treating HF.

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