Empagliflozin (an SGLT-2 inhibitor) demonstrates cardiovascular mortality benefit in diabetic patients with established heart failure. Which mechanism BEST explains its haemodynamic benefit independent of glucose lowering?

• A Reduction in afterload via direct arteriolar vasodilation
• B Beta-1 receptor partial agonism improving cardiac output
• C Inhibition of the cardiac sodium-hydrogen exchanger (NHE-1) directly
• D Osmotic diuresis and natriuresis reducing preload and cardiac filling pressures ✓

Explanation

SGLT-2 inhibitors block sodium-glucose cotransporter-2 in the proximal renal tubule, causing glycosuria along with natriuresis and osmotic diuresis. This reduces circulating volume, lowers ventricular filling pressures (preload), and decreases cardiac wall stress—leading to regression of cardiac fibrosis and improved haemodynamics in heart failure with reduced ejection fraction. Additional proposed mechanisms include haematocrit rise (erythropoietin-like effect) and reduced epicardial fat, but natriuresis/osmotic diuresis is the most established haemodynamic explanation.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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