From Congestion to Cardiorenal Protection: The New Therapeutic Balance Between SGLT2 Inhibitors and Loop Diuretics in Heart Failure

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have redefined the therapeutic landscape of heart failure (HF), both with reduced (HFrEF) and preserved (HFpEF) ejection fraction. Historically, treatment has relied on diuretics to relieve congestion, with limited prognostic impact and dose-related adverse effects. SGLT2i, originally developed for type 2 diabetes mellitus, have demonstrated in randomized trials a significant reduction in hospitalizations and cardiovascular mortality, with benefits extending to non-diabetic patients. SGLT2 inhibitorsTheir mechanism combines moderate osmotic natriuresis, selective reduction of extracellular volume, renal protection, and minimal neurohormonal activation. In contrast to loop diuretics, which induce rapid volume depletion and RAAS activation, SGLT2i stabilize sodium-water balance without significant hemodynamic compromise. In clinical practice, their combination with diuretics requires careful titration to prevent hypovolemia, hypotension, and renal dysfunction, especially in frail elderly patients. Evidence suggests that SGLT2i may reduce chronic diuretic requirements, improve renal function, and provide additional cardiovascular protection. These findings support their early and integrated use, positioning SGLT2i as a cornerstone in the contemporary management of heart failure.