Impact of Metformin on Vitamin B12 Levels in Diabetic Patients

Metformin is the most commonly prescribed oral hypoglycemic drugs and is considered as the first-line treatment for managing non-insulin-dependent diabetes mellitus (T2DM) and is often used alone or in combination with other anti-hyperglycemic agents. While most side effects are generally mild and self-limiting, research has indicated an association between metformin use and reduced vitamin B12 levels in diabetic patients. 

The current review aimed to summarize existing studies on this association, explore potential mechanisms, and identify individual risk factors that may contribute to vitamin B12 deficiency. The primary mechanism by which metformin affects vitamin B12 levels involves its interference with the absorption process; specifically, it disrupts the calcium-dependent binding of the intrinsic factor (IF)-vitamin B12 complex to the ileal cubilin receptor. Several risk factors have been identified, including the duration and dosage of metformin treatment, with longer use correlating with a higher likelihood of deficiency. Male patients generally have lower vitamin B12 levels than females, while Black patients tend to show a lower incidence of deficiency. Additionally, chronic conditions such as T2DM, hyperlipidemia, coronary artery disease, polycystic ovary syndrome (PCOS), obesity, and the use of metformin are significantly associated with an increased risk of vitamin B12 deficiency.

Source: Al Zoubi MS, Al Kreasha R, Aqel S, Saeed A, Al-Qudimat AR, Al-Zoubi RM. Vitamin B12 deficiency in diabetic patients treated with metformin: A narrative review. Ir J Med Sci. 2024 Aug;193(4):1827-1835. doi: 10.1007/s11845-024-03634-4. Epub 2024 Feb 21. PMID: 38381379; PMCID: PMC11294377.