A patient with type 2 diabetes on metformin develops recurrent hypoglycemia after adding a new oral agent. On examination, there is bilateral lower leg edema. The newly added drug is most likely:

• A Sitagliptin (DPP-4 inhibitor)
• B Dapagliflozin (SGLT2 inhibitor)
• C Pioglitazone (thiazolidinedione)
• D Glimepiride (sulfonylurea) ✓

Explanation

Sulfonylureas (glimepiride, glibenclamide, glipizide) stimulate insulin secretion independent of glucose levels by closing KATP channels on pancreatic beta cells, making hypoglycemia the most common significant adverse effect. The leg edema is not directly from glimepiride; however, the combination of hypoglycemia (option D) as the primary feature makes sulfonylurea the most likely culprit. DPP-4 inhibitors and SGLT2 inhibitors carry minimal intrinsic hypoglycemia risk; pioglitazone causes edema but not hypoglycemia as monotherapy.

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

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