Dapagliflozin reduces HbA1c and also has proven cardiovascular and renal benefits in T2DM. Its mechanism is:

• A Inhibition of sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubule, causing glucosuria and natriuresis ✓
• B Stimulation of GLP-1 receptors in pancreatic β-cells, increasing insulin secretion
• C Activation of PPARγ in adipocytes, enhancing peripheral insulin sensitivity
• D Inhibition of DPP-4, prolonging incretin hormone activity

Explanation

SGLT2 accounts for ~90% of renal glucose reabsorption in the proximal tubule S1/S2 segment. Dapagliflozin inhibits SGLT2, causing ~70–80 g/day of glucose to be excreted in urine, lowering plasma glucose insulin-independently. The associated natriuresis reduces preload and afterload (explaining heart failure benefits), and reduced glomerular hyperfiltration explains renoprotection. Euglycaemic DKA is a rare but serious complication. GLP-1 receptor agonists, PPARγ agonists, and DPP-4 inhibitors have distinct mechanisms.

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

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Written and medically reviewed by the StethoPrep medical team.