Effects of metformin on vitamin B12 levels, including dose and duration of therapy: a narrative review

Abstract

Background: Metformin, a biguanide derivative medication, is administered worldwide as the first-line treatment for patients with type 2 diabetes mellitus. Despite its many advantages, it is not devoid of side effects. As many studies have evidenced thus far, metformin treatment may increase the risk of vitamin B12 deficiency, with the prevalence of this deficiency varying from 1.8% to 53.2%. We performed a review of studies to summarize their results and present dose and duration associations between metformin therapy and serum cobalamin levels. Aim of the study: The purpose of this study was to evaluate the relationship between metformin and vitamin B12 deficiency from a historical perspective.Material and Methods: Thirty articles focused on vitamin B12 deficiency during metformin therapy, collected from the PubMed database from 1971 to July 2021, were analyzed.Results: Based on the literature reviewed, we observed a prevalence of vitamin B12 deficiency with metformin use ranging from 1.8% to 53.2%, with a median of 11.2%. In studies with follow-up longer than six months, the incidence of vitamin B12 deficiency during metformin treatment was approximately 6–10%. The vast majority of studies showed an inverse correlation between dose and length of metformin intake and serum vitamin B12 levels. The findings of three out of 16 analyzed studies proved dose-only associations, and the other three showed time-only effects. Two studies found no relationship with these variables.Conclusions: Patients undergoing long-term metformin therapy, especially at high doses, should have their vitamin B12 levels measured regularly to protect them from complications resulting from cobalamin deficiency.