Rewriting the Script: How SGLT2 Inhibitors Are Transforming Heart Failure Care

Abstract: Heart failure (HF) is a major worldwide health concern, with significant morbidity, death, and healthcare expenditures. Traditional therapy sometimes fall short of improving outcomes, particularly in patients with preserved ejection fraction (HFpEF) and concurrent type 2 diabetes mellitus. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, which were first designed for glycaemic management in T2DM, have shown considerable cardiovascular and renal advantages irrespective of glucose reduction. This review examines the evolving role of SGLT2 inhibitors in heart failure care, drawing on key studies such as DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and SOLOIST-WHF. SGLT2 inhibitors, such as dapagliflozin, empagliflozin, and sotagliflozin, have consistently decreased the incidence of cardiovascular mortality and heart failure hospitalisations in patients with reduced and maintained ejection fractions, independent of diabetes status. These medicines enhance myocardial metabolism by improving ketone body utilisation, increasing cardiac efficiency, and decreasing fibrosis and inflammation. They also influence neurohormonal pathways such as the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), anti-diuretic hormone (ADH), and endothelin systems, which help to enhance haemodynamics and fluid balance. Clinical trials have shown benefits in quality of life, symptom load, and renal outcomes, with few adverse events such as hypoglycemia or ketoacidosis. Early usage of SGLT2 inhibitors during heart failure decompensation results in faster symptom alleviation and improved patient outcomes. Finally, SGLT2 inhibitors have emerged as a cornerstone treatment for heart failure, providing advantages to a wide range of individuals. Their inclusion in heart failure recommendations represents a significant change in the management of both HFrEF and HFpEF.

SGLT2 inhibitor, Heart failure, HFrEF, HFpEF, Dapagliflozin, Empagliflozin, Sotagliflozin, Cardiovascular outcomes, Ketone metabolism, RAAS modulation, Neurohormonal regulation, Kansas City Cardiomyopathy Questionnaire (KCCQ), Quality of life, Type 2 diabetes mellitus, Renal outcomes

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