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November 1, 2014

Vitamin B12 deficiency linked to diabetes drug ‘increases over time’

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Diabetic patients treated over prolonged periods with metformin are at risk of developing vitamin B12 deficiency, which is likely to get progressively worse over time, according to a new study.

The researchers suggest that regular measurement of vitamin B12 levels during long-term metformin treatment should be strongly considered.

Metformin is the most commonly prescribed first-line therapy for patients with type II diabetes, according to the authors. Taking metformin can lead to vitamin B12 deficiency and could be associated with decreased folate concentrations.

Researchers from the Netherlands set out to study the effects of metformin treatment on levels of vitamin B12, folate, and homocysteine in 390 patients with type II diabetes.

They gave 850mg of metformin to 196 of the study’s participants and a placebo to the other 194 people three times daily for more than four years. Measures were taken at regular intervals of the patients’ vitamin B12 levels, folate and homocysteine levels.

People who had taken the metformin were found to have a 19 per cent reduction in their vitamin B12 levels, compared with people who had taken a placebo, who had almost no change in their levels. The reduction of vitamin B12 levels by metformin persisted and became more apparent over time.

There was also a significant rise in the number of people with deficient levels of vitamin B12 over the period of the study if they had been taking metformin, from three patients to 19. The equivalent number for the placebo group rose from four patients to five.

Compared with people taking a placebo, people taking metformin also had a 5 per cent increase in homocysteine, but their folate levels were the same once the researchers took body mass index and smoking figures into account. Homocysteine levels increased especially in individuals in whom vitamin B12 levels decreased – showing that the decrease in vitamin B12 levels were functionally meaningful.

BMJ Online, available at http://www.bmj.com/cgi/doi/10.1136/bmj.c2181