A 45-year-old man with type 2 diabetes is switched to dapagliflozin 10 mg daily as monotherapy. What is the mode of action of dapagliflozin?

• A. Reversibly inhibits sodium-glucose co-transporter 2 in the renal proximal tubule to reduce glucose reabsorption and increase urinary glucose excretion
• B. Inhibits DPP-4 to increase incretin levels
• C. Stimulates insulin secretion from pancreas
• D. Inhibits hepatic gluconeogenesis

Answer: (A)

Dapagliflozin works by blocking the sodium-glucose co-transporter 2 (SGLT2) in the kidney’s proximal tubule. Normally, this transporter reabsorbs most of the filtered glucose back into the bloodstream. By inhibiting SGLT2, less glucose is reabsorbed and more is lost in the urine (glucosuria), which lowers blood glucose levels. This mechanism does not rely on stimulating insulin, does not inhibit hepatic glucose production, and is distinct from DPP-4 inhibition. The effect is primarily renal and insulin-independent, with potential benefits like modest weight and blood pressure changes, and risks such as genital infections or volume depletion.