A 62-year-old woman on metformin 1000 mg twice daily for 8 years develops progressive distal numbness and glove-stocking sensory loss. Her HbA1c is well controlled at 6.8%. Serum vitamin B12 level is low. Which mechanism explains her presentation?

• A Metformin induces chronic pancreatitis with malabsorption of cobalamin
• B Metformin interferes with calcium-dependent uptake of the intrinsic factor-B12 complex in the terminal ileum ✓
• C Metformin accelerates renal excretion of transcobalamin-bound B12
• D Metformin directly degrades dietary B12 in the gastric lumen

Explanation

Long-term metformin causes B12 deficiency by interfering with calcium-dependent absorption of the intrinsic factor-cobalamin complex at ileal receptors. Calcium supplementation reverses the effect experimentally, supporting this mechanism. The resulting neuropathy can mimic diabetic peripheral neuropathy, so B12 levels should be checked in metformin-treated patients with unexplained sensory loss even when glycaemic control is good. Renal losses and luminal degradation are not recognised mechanisms, and the condition is unrelated to pancreatic function.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.