Vitamin B12 deficiency in diabetic patients treated with metformin: A narrative review
Mazhar Salim Al Zoubi, Rasha Al Kreasha, Sarah Aqel, Ahmad Saeed, Ahmad R. Al‐Qudimat, Raed M. Al‐Zoubi
Abstract
Abstract Metformin is the most prescribed oral hypoglycemic drug and is considered by many health practitioners as the first-line treatment for non-insulin-dependent diabetes mellitus (T2DM). It is used either as a monotherapy or adjuvant to other anti-hyperglycemic agents. Most of its side effects are usually mild and self-limiting. However, several studies have shown an association between the use of metformin and low vitamin B 12 levels in diabetic patients. The current review aimed to provide a literature review of the current published reports on the association, the possible mechanisms, and the related individualized risk factors that might lead to this incidence. The most accepted mechanism of the effect of metformin on vitamin B 12 level is related to the absorption process where metformin antagonism of the calcium cation and interference with the calcium-dependent IF-vitamin B 12 complex binding to the ileal cubilin receptor. In addition, many risk factors have been associated with the impact of metformin on vitamin B 12 levels in diabetic patients such as dose and duration where longer durations showed a greater prevalence of developing vitamin B 12 deficiency. Male patients showed lower levels of vitamin B 12 compared to females. Black race showed a lower prevalence of vitamin B 12 deficiency in metformin-treated patients. Moreover, chronic diseases including T2DM, hyperlipidemia, coronary artery disease, polycystic ovary disease (PCOD), obesity, and metformin therapy were significantly associated with increased risk of vitamin B 12 deficiency. Graphical abstract Metformin impacts vitamin B 12 by (A) inhibiting calcium-dependent IF-B12 binding. (B) Prolonged use raises deficiency risk. (C) Males have lower B12 levels than females. (D) Black individuals show lower deficiency rates. (E) Conditions like T2DM, hyperlipidemia, coronary artery disease, PCOD, obesity, and metformin use heighten deficiency risk.