Metformin use may cause vitamin B-12 deficiency

January 01, 0001

Metformin use may cause vitamin B-12 deficiency

This group of Dutch and Belgian researchers examined the effects of metformin on vitamin B-12 levels. They performed a multicentre randomised placebo controlled trial enrolling 390 type 2 diabetics who used insulin Participants were randonmized to 850 mg metformin or placebo three times a day for over 4 years. They measured vitamin B-12, folate, and homocysteine concentrations from baseline at 4, 17, 30, 43, and 52 months.

The researchers report: "Compared with placebo, metformin treatment was associated with a mean decrease in vitamin B-12 concentration of -19 percent and in folate concentration of -5 percent, and an increase in homocysteine concentration of 5 percent. After adjustment for body mass index and smoking, no significant effect of metformin on folate concentrations was found. The absolute risk of vitamin B-12 deficiency (less than 150 pmol/l) at study end was 7.2 percentage points higher in the metformin group than in the placebo group, with a number needed to harm of 13.8 per 4.3 years. The absolute risk of low vitamin B-12 concentration (150-220 pmol/l) at study end was 11.2 percentage points higher in the metformin group, with a number needed to harm of 8.9 per 4.3 years. Patients with vitamin B-12 deficiency at study end had a mean homocysteine level of 23.7 µmol/l, compared with a mean homocysteine level of 18.1 µmol/l for patients with a low vitamin B-12 concentration and 14.9 µmol/l compared with vitamin B-12 deficiency."

The authors concluded: "Long term treatment with metformin increases the risk of vitamin B-12 deficiency, which results in raised homocysteine concentrations. Vitamin B-12 deficiency is preventable; therefore, our findings suggest that regular measurement of vitamin B-12 concentrations during long term metformin treatment should be strongly considered."

This study finds evidence that metformin use may lead to vitamin B-12 deficiency and suggests that this side effect should be tested for routinely.

For the full abstract, click here.

BMJ 340:c2181, 20 May 2010
© 2010 de Jager et al.
Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. Jolien de Jager, Adriaan Kooy, Philippe Lehert, et al. Correspondence to C D A Stehouwer:

Category: T. Endocrine/Metabolic/Nutritional. Keywords: vitamin B-12, folate, homocysteine, metformin, diabetes, randomized controlled trial, journal watch.
Synopsis edited by Dr Paul Schaefer, Toledo, Ohio. Posted on Global Family Doctor 6 July 2010

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