A 65-year-old man has taken metformin 1 g twice daily for eight years. He now reports numbness of both feet, and blood counts show macrocytic anaemia with low serum vitamin B12. The mechanism of metformin-induced B12 deficiency is:

• A Direct destruction of intrinsic factor by metformin in the stomach
• B Accelerated hepatic consumption of stored B12
• C Competitive inhibition of B12 absorption by the biguanide moiety
• D Interference with calcium-dependent uptake of the B12-intrinsic factor complex in the ileum ✓

Explanation

Long-term metformin interferes with the calcium-dependent process by which the vitamin D12-intrinsic factor complex is absorbed at the terminal ileum, producing malabsorption over years of therapy. Supplementation with periodic D12 monitoring is advised in patients on prolonged treatment. It is not related to intrinsic factor destruction, competitive blockade or altered storage, and the resulting neuropathy can mimic diabetic peripheral neuropathy.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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Written and medically reviewed by the StethoPrep medical team.