Long-term Metformin Use Linked to Vitamin B12 Deficiency

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Patients treated with metformin for diabetes are at a higher risk for developing a vitamin B12 deficiency, according to new research published in the journal BMJ. Metformin is the most commonly prescribed first-line therapy for patients with type 2 diabetes, and is sold under such brand names as Glucophage, Fortamet, Glumetza, and Riomet.

Researchers from the Academic Medical Center in the Netherlands gave 850 milligrams of metformin to 196 study participants three times daily for more than four years. Another 194 received placebos. During the study period, measures of the patients B12, folate, and homocysteine levels were taken.

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The participants taking metformin were found to have a 19% reduction in their vitamin B12 levels compared with those who had taken the placebo, who had almost no change in vitamin levels. In addition, the reduction of B12 persisted over time with an increase in symptoms.

Vitamin B12 is an essential water-soluble vitamin that is mainly found in animal foods such as fish, meat and dairy products. It helps to maintain healthy nerve cells and red blood cells, among other functions. Symptoms of B12 deficiency include fatigue, mental changes, anemia, and neuropathy. Because these symptoms are similar to those of uncontrolled diabetes or related to aging, the deficiency sometimes goes undiagnosed.

Vitamin B12 also works with other vitamins, such as folate and vitamin B6, to control levels of homocysteine in the body. Homocysteine is an amino acid in the blood and elevated levels have been shown to increase the risk of coronary heart disease, stroke and peripheral vascular disease. In the study, those taking metformin who had experienced a reduction in B12 also had an increase in homocysteine levels.

The authors say: "Our study shows that it is reasonable to assume harm will eventually occur in some patients with metformin-induced low vitamin B12 levels." For this reason, they suggest that physicians regularly monitor B12 levels during long-term metformin treatment.

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