Is it necessary to be afraid of vitamin B12 deficiency during metformin treatment?

Metformin, a biguanide derivative, is the most frequently used antihyperglycaemic agent in the world. Various adverse effects can occur during the drug therapy. One of them is vitamin B12 deficiency, which may be either asymptomatic (biochemical) or may lead to neurological and/or haematological disorders. Causal diagnosis of these disorders is hampered due to the fact that nervous system symptoms are similar to neurological complications developing over the course of diabetes mellitus. It is estimated that 5.8 to 33% of metformin treated patients have a low (below the reference level) serum vitamin B12 concentration. The interrelation between vitamin B12 deficiency and metformin usage has been known for decades and over that time many studies have been carried out to assess the issue. Unfortunately, these studies were mainly observational, retrospective and performed on nonhomogeneous groups of patients. Recently a meta-analysis of studies concerning only diabetic patients was performed and it demonstrated the existence of a relationship between metformin treatment and vitamin B12 deficiency. Nevertheless, further well-designed, large-scale, randomized studies performed on a homogenous group of patients and employing homogenous criteria for diagnosing vitamin B12 deficiency are necessary in order to decide whether serum vitamin B12 concentration should be routinely checked among metformin treated patients