Metformin induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes

Metformin blocks the absorption of vitamin B12 through a mechanism that has not been established. Still, it could be due to interference with the calcium‐dependent binding of the intrinsic factor‐ vitamin B12 complex to the cubam receptor in the terminal ileum. The subsequent deficiency of vitamin B12 may cause or accelerate distal symmetrical and autonomic neuropathy in diabetic patients. Several observational studies and meta‐analyses have reported a significant association between metformin utilization and vitamin B12 deficiency. Prospective studies have shown that metformin utilizers have lower vitamin B12 levels. Still, they also have higher frequencies of distal symmetrical polyneuropathy and autonomic neuropathy. Therefore, periodic monitoring of vitamin B12 is recommended in all patients who utilize metformin, especially if metformin has been used for over five years.