What is the primary mechanism of SGLT2 inhibitors?

• A. Stimulate pancreatic insulin secretion
• B. Inhibit intestinal glucose absorption
• C. Inhibit renal glucose reabsorption in the proximal tubule, causing glucosuria and lower plasma glucose
• D. Increase peripheral insulin sensitivity

Answer: (C)

Blocking the kidney’s ability to reabsorb glucose in the proximal tubule is the primary action. SGLT2 inhibitors target the sodium-glucose co-transporter 2, which normally reclaims most of the filtered glucose from the urine back into the blood. Inhibiting this transporter causes glucose to spill into the urine (glucosuria), which lowers plasma glucose levels. This effect happens independently of insulin and is accompanied by mild osmotic diuresis and some weight loss.

Other options describe actions that aren’t how SGLT2 inhibitors work: stimulating pancreatic insulin secretion, inhibiting intestinal glucose absorption, or improving insulin sensitivity.