Background/Purpose: Type 2 diabetes mellitus (T2DM) is a worldwide pathology with several complications, and 50% of patients with T2DM develop peripheral neuropathy (PN) in the long term. The present study aimed to review the literature on the association between PN and vitamin B12 deficiency in patients with T2DM treated with metformin. Materials and methods: A literature review was carried out in the PubMed Central, Cochrane, Scielo, Scopus and Embase databases, from 2015 to 2021. We found 755 studies, of which 16 were included. Results: The serum level of vitamin B12 was lower in individuals with at least one neurological symptom. Treatment with metformin was associated with reduced serum vitamin B12 levels, and its use was defined as a probable cause of PN due to reduced vitamin B12. Studies that performed supplementation with methylcobalamin demonstrated significant improvement in neuropathic symptoms. Vitamin B12 supplementation therapy for diabetic patients undergoing metformin treatment has been suggested. Conclusion: Deficiency of vitamin B12 associated to metformin can be considered a risk factor for PN. Periodically evaluation of serum levels of vitamin B12 is recommended for patients on metformin treatment.
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