An SGLT-2 inhibitor is prescribed to a diabetic patient with heart failure with reduced ejection fraction. Beyond glycaemic control, the direct cardiac benefit is attributed to:

• A ACE-inhibitor-like reduction in angiotensin II levels reducing cardiac afterload
• B Direct GLP-1 receptor stimulation in cardiomyocytes increasing contractility
• C Inhibition of the late INa channel reducing intracellular calcium overload in cardiomyocytes
• D Natriuresis and osmotic diuresis reducing cardiac preload, and a possible switch to ketone bodies as a more oxygen-efficient myocardial fuel ✓

Explanation

SGLT-2 inhibitors reduce cardiac preload and afterload via glucosuria-driven osmotic diuresis and natriuresis. Additionally, they promote mild ketonaemia; ketone bodies (beta-hydroxybutyrate) are a more oxygen-efficient cardiac fuel than glucose or fatty acids, offering direct energetic benefit to the failing myocardium. They also reduce myocardial fibrosis and oxidative stress. GLP-1 receptor agonists (not SGLT-2 inhibitors) act via GLP-1R.

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

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