An 82-year-old woman with eGFR 28 mL/min/1.73 m² was given glibenclamide for type 2 diabetes. Two days later she is found drowsy with glucose 38 mg/dL requiring repeated dextrose infusions over 48 hours. Which property of glibenclamide best explains this course?
- A It stimulates GLP-1 release, causing delayed insulin secretion
- B It inhibits renal gluconeogenesis independently of insulin
- C Its active metabolites accumulate in renal failure and its long receptor binding prolongs insulin release ✓
- D It blocks counter-regulatory glucagon release at the alpha cell
Correct answer: C. Its active metabolites accumulate in renal failure and its long receptor binding prolongs insulin release
Explanation
Glibenclamide (glyburide) closes beta-cell KATP channels via SUR1, and its metabolites retain hypoglycaemic activity while being partly renally cleared, so accumulation in elderly patients with low eGFR drives prolonged, recurrent hypoglycaemia lasting days. This is why short-acting agents such as glipizide, or drugs avoiding hypoglycaemia entirely, are preferred in renal impairment. It does not act through GLP-1, renal gluconeogenesis, or glucagon blockade.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
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