Metformin reduces intestinal absorption of vitamin B12 by up to 30%. The mechanism is thought to involve impaired calcium-dependent binding of the intrinsic factor-B12 complex to its receptor, thus decreasing ileal absorption. The risk of developing vitamin B12 deficiency increases with older patients, higher metformin doses, and longer durations of treatment. Neurologic symptoms may appear before anemia develops.
Small amounts of vitamin B12 present in daily multivitamin supplements do not protect against the development of vitamin B12 deficiency in metformin-treated patients. As a result, patients taking metformin should be routinely monitored for B12 deficiency. Increased calcium intake may improve vitamin B12 absorption.