Empagliflozin reduces cardiovascular mortality and hospitalisation for heart failure in diabetic patients independently of its glycaemic effect. The most widely accepted mechanism for its cardioprotective benefit is:

• A Osmotic diuresis and natriuresis leading to reduced plasma volume, cardiac preload, and ventricular wall stress, combined with reduction in late Na current in cardiomyocytes ✓
• B Reduction of visceral adiposity reducing pericardial fat and myocardial inflammation
• C SGLT2 inhibition in the kidney directly triggering release of atrial natriuretic peptide
• D Competitive inhibition of SGLT1 in the gut reducing glucose-dependent GLP-1 secretion and insulin secretion

Explanation

SGLT2 inhibitors produce sustained natriuresis and osmotic diuresis (reduction in plasma volume and interstitial fluid), lowering preload and afterload — haemodynamic benefits particularly important in heart failure. Additionally, emerging evidence supports direct myocardial effects: inhibition of the late (persistent) Na+ current (NHE-Na+ mediated) in cardiomyocytes reduces intracellular Ca2+ overload and diastolic dysfunction. The diuretic/haemodynamic effect acts rapidly, whereas anti-inflammatory and metabolic effects are longer-term. SGLT2 inhibitors are not linked to ANP release, and their gut SGLT1 effect (minor) does not explain cardiac benefits.

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

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Written and medically reviewed by the StethoPrep medical team.