Long-Term Metformin Raises Risk for B12 Deficiency

Metformin -- the most commonly prescribed oral drug for patients with Type 2 diabetes -- induces vitamin B₁₂ malabsorption and therefore can raise risk for vitamin B₁₂ deficiency. In this multicenter randomized trial, Dutch investigators assessed risk for B₁₂ deficiency (blood level, <150 pmol/L), low vitamin B₁₂ level (blood level, 150–220 pmol/L), and elevated blood homocysteine levels in patients with Type 2 diabetes who were treated with metformin. 

Overall, 390 patients received metformin (850 mg) or placebo three times daily for 4.3 years. Compared with placebo, metformin was associated with a significant 19% decrease in baseline vitamin B₁₂ concentration. The absolute risks for vitamin B₁₂ deficiency and low vitamin B₁₂ level were significantly higher in the metformin group than in the placebo group: 7% and 11% higher, with numbers needed to harm of 14 and 9 per 4.3 years, respectively. Blood homocysteine levels were correspondingly and significantly elevated. Notably, the effect of metformin on lowering B₁₂ levels increased with duration of therapy.

That metformin use is associated with lower blood B₁₂ levels has been observed previously (JW Gen Med Mar 15 2010, p. 49, and Diabetes Care 2010; 33:156). However, this trial shows that metformin use raises risks for B₁₂ deficiency, low B₁₂ levels, and high homocysteine levels. Because B₁₂ deficiency can result in anemia, neuropathy, and cognitive changes and because elevated blood homocysteine level is a risk factor for cardiovascular disease, the authors recommend routine monitoring of B₁₂ levels in patients who receive metformin. Whether B₁₂ supplementation prevents B₁₂ deficiency in such patients is unknown.

de Jager J et al. Long term treatment with metformin in patients with Type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial. BMJ 2010 May 20; 340:c2181. (http://dx.doi.org/10.1136/bmj.c2181)