Dapagliflozin reduces HbA1c in type 2 diabetes by a mechanism entirely independent of insulin secretion or action. This mechanism is:

• A Inhibition of intestinal alpha-glucosidase delaying glucose absorption
• B Blockade of renal proximal tubule SGLT2 co-transporter causing urinary glucose excretion ✓
• C Activation of AMPK in skeletal muscle promoting glucose uptake independent of insulin
• D Inhibition of DPP-4 enzyme increasing active GLP-1 and GIP levels

Explanation

Dapagliflozin inhibits SGLT2 (sodium-glucose co-transporter 2) in the proximal convoluted tubule of the kidney, which normally reabsorbs ~90% of filtered glucose. By blocking SGLT2, approximately 60–80 g of glucose is excreted in urine daily, lowering blood glucose independent of insulin. This mechanism is insulin-independent, making it effective even in advanced beta-cell failure, and also produces osmotic diuresis and caloric loss contributing to weight reduction and blood pressure lowering.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.