Metformin and Vitamin B12: An insight into the Hidden Deficiency in Diabetic Patients

Metformin is the most commonly prescribed oral hypoglycemic drug and is considered as the first-line treatment for non-insulin-dependent diabetes mellitus (T2DM). It is either used as a monotherapy or adjuvant to other anti-hyperglycemic drugs. While it generally has mild and self-limiting side effects, studies have linked its use to low vitamin B12 levels in diabetic patients.

The present review examined the literature on this association, potential mechanisms, and individual risk factors contributing to vitamin B12 deficiency. The primary mechanism of the effect of metformin on vitamin B12 level involves metformin's interference with the absorption of vitamin B12 by antagonizing calcium and disrupting the binding of the vitamin B12-intrinsic factor complex to the ileal cubilin receptor in the intestines. Several factors such as higher doses and prolonged use of metformin increase the risk of deficiency of vitamin B12 in diabetic patients, with males typically having lower vitamin B12 levels than females. Interestingly, Black patients tend to have a lower prevalence of vitamin B12 deficiency in metformin-treated patients. Additionally, chronic conditions like T2DM, hyperlipidemia, coronary artery disease, polycystic ovary disease (PCOD), and obesity further elevate the risk of vitamin B12 deficiency in patients undergoing metformin therapy.

Nonetheless, the advantages outweigh the potential risks of vitamin B12 deficiency. The experts encouraged physicians and healthcare practitioners to remain vigilant about these side effects. Other studies have also recommended routine monitoring of vitamin B12 levels in patients undergoing long-term metformin therapy, among a few suggested the regular checks for doses exceeding 1000 to 2000 mg per day, while others did not specify particular dosages or durations. 

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.