A 58-year-old man with type 2 diabetes and a history of heart failure with reduced ejection fraction (HFrEF) is started on empagliflozin. Beyond glucose lowering, the cardiovascular benefit of SGLT-2 inhibitors in HFrEF is BEST explained by:

• A Direct positive inotropic effect on cardiomyocytes via intracellular Na+ reduction
• B Osmotic diuresis and natriuresis reducing preload, and metabolic shift to ketone bodies improving cardiac energetics ✓
• C Inhibition of the renin-angiotensin-aldosterone system reducing afterload
• D Stimulation of erythropoietin production increasing oxygen-carrying capacity

Explanation

SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) reduce cardiovascular hospitalizations and mortality in HFrEF through multiple mechanisms. Glucosuria-driven osmotic diuresis and natriuresis reduce intravascular volume and cardiac preload. The resulting mild ketonemia shifts myocardial substrate utilization toward ketone bodies—a more oxygen-efficient fuel—improving cardiac energetics. Additionally, SGLT-2 inhibitors may reduce epicardial fat mass and inflammation. Erythropoietin stimulation (increasing haematocrit) is a real but secondary effect. The heart failure benefit occurs independently of glycaemic status.

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

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Written and medically reviewed by the StethoPrep medical team.