Long-term Metformin Treatment Associated with Reduced Vitamin B12 Levels

DynaMed Weekly Update - Volume 5, Issue 23

Metformin is a commonly prescribed first-line treatment for type 2 diabetes that not only lowers blood glucose concentrations but also may reduce cardiovascular mortality when used as monotherapy or in combination with sulfonylureas. Metformin has previously been linked to reduced vitamin B12 levels, but a new randomized trial with 390 patients is the first to look at the long-term relationship. Patients (mean age 62 years) with type 2 diabetes who were receiving insulin therapy were randomized to metformin 850 mg vs. placebo 3 times daily for 4.3 years. Vitamin B12 deficiency was defined as serum concentration < 150 pmol/L (203.3 pg/mL), and concentration > 220 pmol/L (298 pg/mL) was considered normal. In an analysis of the 71% of patients who completed the trial, the metformin group had a significantly higher incidence of both vitamin B12 deficiency (9.9% vs. 2.7%, p = 0.004, NNH 13.8 per 4.3 years) and below-normal vitamin B12 levels (18.2% vs. 7%, p = 0.001, NNH 8.9 per 4.3 years) ( level 3 [lacking direct] evidence). Metformin was also associated with a trend toward increased homocysteine levels (mean change 3.26 mcmol/L vs. 1.6 mcmol/L, p = 0.091).

The effect of metformin on vitamin B12 levels increased with treatment duration. The authors suggest regular monitoring of vitamin B12 levels for patients receiving long-term metformin treatment (BMJ 2010 May 20;340:c2181).

For more information, see the Metformin topic in DynaMed.