Sodium glucose transporter 2 inhibitors for heart failure

Abstract

Heart failure (HF) is a leading cause of cardiovascular morbidity and mortality, affecting over 64 million individuals worldwide. Despite advances in guideline-directed medical therapy, patients with HF continue to experience poor outcomes, highlighting the need for novel therapeutic approaches. Sodium glucose transporter 2 (SGLT2) inhibitors, initially developed for diabetes management, have emerged as groundbreaking therapies for HF. These agents demonstrate remarkable cardiovascular benefits that extend beyond their glucose-lowering effects, including significant reductions in HF hospitalization and cardiovascular mortality rates. Landmark trials including Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure, Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction, Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction, and Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure have established the efficacy of SGLT2 inhibitors across the spectrum of HF phenotypes, regardless of diabetes status. The mechanisms underlying these benefits are multifaceted, involving improvements in cardiac energetics, mitochondrial function, reduction of oxidative stress, attenuation of inflammation, and favorable effects on cardiac remodeling and fibrosis. This comprehensive review examines the current evidence supporting the use of SGLT2 inhibitors in HF management, explores the mechanistic pathways responsible for their cardiovascular benefits, analyzes key clinical trial data, and discusses future prospects for this transformative drug class in cardiovascular medicine.

Keywords: Sodium glucose transporter 2 inhibitor; Heart failure; Cardiovascular benefit; Mechanistic pathway; Current evidence; Prospects

Core Tip: Heart failure (HF) affects over 64 million people worldwide, with persistently poor outcomes despite advances in treatment. Sodium glucose transporter 2 inhibitors, originally developed for diabetes, have emerged as breakthrough HF therapies with cardiovascular benefits beyond glucose control, including reduced risk of hospitalization and mortality. Landmark trials (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure, Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction, Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction, Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) have demonstrated efficacy across all HF types, regardless of diabetes status. Their benefits stem from improved cardiac energetics, enhanced mitochondrial function, reduced oxidative stress and inflammation, and favorable cardiac remodeling. This review examines current evidence, mechanistic pathways, and future prospects for sodium glucose transporter 2 inhibitor use in cardiovascular medicine.