Alvarez M, Prieto AE, Portilla N, Moya D, Rincon O, Guzman I. Metformin-induced vitamin B12 deficiency: An underdiagnosed cause of diabetic neuropathy. World J Diabetes 2025; 16(7): 107514 [DOI: 10.4239/wjd.v16.i7.107514]
Corresponding Author of This Article
Mauricio Alvarez, MD, Department of Endocrinology, Hospital Militar Central, Carrera 7a n 94 a 47, Bogotá 110221, Colombia. mauricioalvarez613@gmail.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Jul 15, 2025; 16(7): 107514 Published online Jul 15, 2025. doi: 10.4239/wjd.v16.i7.107514
Metformin-induced vitamin B12 deficiency: An underdiagnosed cause of diabetic neuropathy
Mauricio Alvarez, Andres E Prieto, Natalia Portilla, Diana Moya, Oswaldo Rincon, Isaac Guzman
Mauricio Alvarez, Natalia Portilla, Oswaldo Rincon, Isaac Guzman, Department of Endocrinology, Hospital Militar Central, Bogotá 110221, Colombia
Andres E Prieto, Internal Medicine Program, University Militar Nueva Granada, Bogotá 110221, Colombia
Diana Moya, Internal Medicine Program, University de la Sabana, Bogotá 110221, Colombia
Author contributions: Alvarez M, Prieto AE, Portilla N, Moya D, Rincon O, and Guzman I contributed to the preparation of the manuscript and approved its final content.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mauricio Alvarez, MD, Department of Endocrinology, Hospital Militar Central, Carrera 7a n 94 a 47, Bogotá 110221, Colombia. mauricioalvarez613@gmail.com
Received: March 25, 2025 Revised: April 24, 2025 Accepted: June 11, 2025 Published online: July 15, 2025 Processing time: 112 Days and 12 Hours
Abstract
Metformin-induced vitamin B12 deficiency is a prevalent condition among patients with type 2 diabetes mellitus. In recent years, a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset, progression, and worsening of diabetic neuropathy (DNP) as well as its improvement with supplementation in cases of deficiency. Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measurement and supplementation, and some guidelines do not address it at all. Given that vitamin B12 therapy is an economical, safe, and widely available treatment in most countries and supported by emerging evidence of its potential benefits, greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency. Vitamin B12 deficiency should be treated in all affected patients, and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable. Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.
Core Tip: Metformin-induced vitamin B12 deficiency is common in type 2 diabetes and is increasingly linked to diabetic neuropathy. Despite emerging evidence supporting screening and supplementation, major clinical guidelines provide inconsistent recommendations. Given the safety, affordability, and potential benefits of vitamin B12, systematic screening should be prioritized in patients with diabetes at risk of deficiency, especially those with neuropathy.
