SGLT2 inhibitors + sacubitril + valsartan

SGLT2 inhibitors + sacubitril + valsartan is a combination therapy consisting of: - An SGLT2 inhibitor (such as empagliflozin or dapagliflozin), a class of small molecules that inhibit sodium-glucose cotransporter 2 in the kidney to promote glycosuria and natriuresis, offering cardiovascular benefits and reducing the risk of hospitalization and mortality in heart failure. - Sacubitril/valsartan, a fixed-dose angiotensin receptor-neprilysin inhibitor that combines a neprilysin inhibitor (sacubitril) and an angiotensin II receptor blocker (valsartan), resulting in vasodilatory, natriuretic, and anti-fibrotic effects with proven benefits in heart failure with reduced ejection fraction. The combined regimen is used as advanced therapy for heart failure (especially with reduced ejection fraction), with evidence that the combination provides additive or synergistic cardiovascular protection beyond either agent alone[5][3][7][11]. The precise mechanism involves: - **SGLT2 inhibitors**: promote renal excretion of glucose and sodium, reducing preload, afterload, and improving cardiac metabolism. - **Sacubitril**: inhibits neprilysin, increasing levels of natriuretic peptides, bradykinin, and adrenomedullin, leading to vasodilatation and diuresis. - **Valsartan**: blocks the angiotensin II type 1 receptor, suppressing vasoconstriction and aldosterone secretion, lowering blood pressure and preventing cardiac remodeling[2][4][6][9]. This combination does not exist as a single fixed-dose product, but as individual drugs administered together in practice.