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SGLT2i Mechanism of Action — RACP Adult Medicine MCQ

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EasyEndocrinology & DiabetesSGLT2i Mechanism of ActionRACP Adult Medicine

A 60-year-old man with type 2 diabetes on empagliflozin and metformin develops a urinary tract infection. Urine dipstick shows glucose 4+ but his blood glucose is 7.5 mmol/L (normal). What is the explanation?

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Correct answer: C — Overflow glycosuria from hyperglycaemia

SGLT2 inhibitors (empagliflozin, dapagliflozin) work by blocking glucose reabsorption in the proximal renal tubule, causing therapeutic glycosuria (~70 g/day of glucose excretion). This is the MECHANISM of action, not an adverse effect. The glycosuria is expected and persists as long as the drug is taken with adequate renal function. However, the glycosuria creates a substrate for bacterial and fungal growth, explaining the increased risk of UTIs (particularly genital mycotic infections – vulvovaginal candidiasis in women, balanitis in men) and the rare but serious Fournier gangrene.

Reference: AMH – 2025 – SGLT2 Inhibitors; eTG – 2025 – Endocrinology