Vahid, Samin Sadegh S; Jahromi, Marziyeh Saleh S; Moukarbel, George V; Hill, Jennifer W
description
Sodium-glucose co-transporter-2 (SGLT2) inhibitors have become a cornerstone of heart-failure (HF) therapy, lowering hospitalization and cardiovascular mortality in patients with and without diabetes across the spectrum of ejection-fraction phenotypes. Their cardioprotective effects extend beyond glycemic control and are best explained by a hierarchy of mechanisms initiated in the kidney. Early tubular inhibition restores tubuloglomerular feedback, producing osmotic diuresis, natriuresis, and modest reductions in plasma volume and blood pressure that together relieve ventricular preload and afterload. These renal and hemodynamic actions are followed by sustained adaptations involving neurohormonal modulation, erythropoiesis, improved cortical oxygenation, and progressive anti-inflammatory, antifibrotic, and mitochondrial effects. Through these interrelated pathways, SGLT2 inhibition preserves kidney function, limits congestion, and promotes cardiac reverse remodeling. Recognizing that these mechanisms act sequentially and in parallel clarifies how SGLT2 inhibitors complement standard therapies and guides ongoing mechanistic studies to refine their role in HF management.
