SGLT2 inhibitors act in which part of the nephron to block glucose reabsorption?

• A. Proximal tubule
• B. Distal tubule
• C. Loop of Henle
• D. Collecting duct

Answer: (A)

SGLT2 inhibitors work where most filtered glucose is reabsorbed: the proximal tubule. In the early proximal tubule (the S1/S2 segments), the sodium-glucose cotransporter 2 reclaims the bulk of glucose from the filtrate back into the bloodstream. Blocking this transporter with SGLT2 inhibitors prevents this reabsorption, so glucose remains in the tubular fluid and is excreted in urine (glucosuria). This is why the proximal tubule is the site of action, not the distal tubule, loop of Henle, or collecting duct. The remaining glucose reabsorption in the distal segments is handled by SGLT1, which is not the primary target of these drugs.