A 61-year-old man with type 2 diabetes on metformin 1000 mg twice daily for 8 years develops distal numbness and a macrocytic anaemia. Serum vitamin B12 is 148 pg/mL. What is the mechanism?
- A Metformin inhibits calcium-dependent absorption of the B12 intrinsic factor complex in the terminal ileum ✓
- B Metformin induces intrinsic factor antibodies
- C Metformin competes with B12 for renal tubular reabsorption
- D Metformin accelerates hepatic consumption of B12 stores
Correct answer: A. Metformin inhibits calcium-dependent absorption of the B12 intrinsic factor complex in the terminal ileum
Explanation
Long-term metformin interferes with the ileal uptake of the vitamin A12 intrinsic factor complex in a calcium-dependent manner; calcium supplementation reverses the malabsorption experimentally, supporting this mechanism. Prevalence of deficiency rises with dose and duration beyond four years, and it can mimic or worsen diabetic peripheral neuropathy, so periodic A12 monitoring is advised. Pernicious anaemia involves intrinsic factor antibodies but is unrelated to metformin. Renal handling and hepatic turnover do not explain the deficiency.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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