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Long-term metformin can lead to low vitamin B12

By Lilian Anekwe

Long-term metformin therapy can lead to vitamin B12 deficiency in patients with diabetes, according to a randomised controlled trial in patients with type 2 diabetes.

390 patients with type 2 diabetes who receiving insulin therapy were randomised to receiving either 850mg of metformin of placebo three times a day for 4.3 years, and the percentage change in their vitamin B12, folate and homocysteine concentrations from baselines were measured at 4,l 17, 30, 43 and 52 months.

During metformin treatment, vitamin B12 decreased by 89.9pmol/l, or 19%, whereas folate concentration increased by 0.21nmol/l or 3% overall and homocysteine levels increased by 3.3µmol/l or 26%.

The absolute risk of vitamin B12 deficiency, defined as a blood concentration of less then 150pmol/l, was 7.2% higher in the metformin group than in the placebo group.

Professor Coen Stehouwer, chair of internal medicine at Maastricht University, concluded: ‘Long term treatment with metformin increases the risk of vitamin B12 deficiency, which results in raised homocysteine concentration.

‘Vitamin B12 deficiency is preventable, therefore our findings suggest that regular measurement of vitamin B12 concentrations during long term metformin treatment should be strongly considered.'

BMJ published online 21 May

Long-term metformin can lead to low vitamin B12


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