A patient with type 2 diabetes and heart failure is started on dapagliflozin. The osmotic and natriuretic effects of SGLT2 inhibitors are primarily due to which mechanism?

• A Inhibition of sodium reabsorption in the thick ascending limb of Henle
• B Inhibition of glucose and sodium reabsorption in the proximal convoluted tubule ✓
• C Blockade of the Na-Cl cotransporter in the distal convoluted tubule
• D Osmotic inhibition of water reabsorption in the collecting duct

Explanation

SGLT2 inhibitors block the sodium-glucose cotransporter 2 in the early proximal convoluted tubule, preventing reabsorption of approximately 90% of filtered glucose. The unreabsorbed glucose acts as an osmotic agent, drawing water and sodium into the tubular lumen, producing osmotic diuresis and natriuresis. This mechanism reduces both plasma volume and glycemia. The other options describe sites of action of loop diuretics, thiazides, and osmotic diuretics respectively.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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