A popular diabetes drug has been shown in a new study to increase the risk for vitamin B12 deficiency and anemia when taken over several years.
Metformin (generic name: glucophage) is a drug prescribed to people with Type 2 diabetes to help control the amount of sugar (glucose) in the blood by reducing how much glucose is absorbed from food and produced by the liver. The medication also increases the body’s response to insulin.
Senior study author Dr. Jill P. Crandall of Albert Einstein College of Medicine in New York City told Reuters in an email:
“Metformin is the most commonly used drug to treat type 2 diabetes, so many millions of people are taking it, usually for a prolonged period (many years).”
Crandall added that some people also take the drug to prevent diabetes, and to treat polycystic ovarian syndrome (PCOS), one of the most common causes of female infertility.
For the study, Crandall and her team looked at data from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study, which followed individuals at high risk for Type 2 diabetes for more than a decade.
At the start of the study, more than 3,000 participants age 25 years and older had high blood sugar. They were randomly assigned to receive either 850 milligrams of metformin twice daily, placebo medication, or an intensive lifestyle program not including medication. Only those taking metformin were included in the new analysis, and about 50 participants were excluded who had undergone weight-loss surgery, which would affect their diabetes outcomes.
Researchers took blood samples from the participants at the 5- and 13-year follow-ups. These samples helped the team conclude that at year 5, average B12 levels were lower in the metformin group than the placebo group, and B12 deficiency was more common, affecting about 4% of participants on metformin, compared to 2% of those not taking the drug.
Approximately 20% of metformin users and 10% of non-users had borderline low B12 levels.
Average B12 levels were higher at the 13-year-point than at 5 years, but B12 deficiency was also found to be more common in both the metformin and the placebo groups.
At 5 years, more of the metformin patients had anemia than the placebo group, as well.
Monthly Prescribing Reference explains:
“The currently accepted explanation for the B12 deficiency is caused by the interference of metformin on calcium-dependent membrane action responsible for vitamin B12- intrinsic factor absorption in the terminal ileum. The authors note that although evidence points to metformin exposure creating low B12 levels, assessment of levels in individuals treated with metformin has not been incorporated into practice guidelines.”
The human body does not produce vitamin B12. We must get it from either supplements or animal sources, such as eggs, dairy products, and fortified grains. A B12 deficiency can lead to anemia, as well as cause brain and nerve damage. The vitamin also helps us absorb folic acid. People with low vitamin B12 levels are more likely to brain shrinkage and cognitive decline. 
The team concluded that “understanding the potential adverse consequences of metformin treatment is essential,” and that “routine measurement of vitamin B12 for metformin-treated individuals should be considered.”
“The FDA and organizations such as the American Diabetes Association do not have any formal recommendations for B12 monitoring for people taking metformin. That said, our study (and others) suggests that a small but significant number of people may develop deficiency.
“People who are taking metformin should ask their doctor about measuring their B12 level.”
Julie Fidler is a freelance writer, legal blogger, and the author of Adventures in Holy Matrimony: For Better or the Absolute Worst. She lives in Pennsylvania with her husband and two ridiculously spoiled cats. She occasionally pontificates on her blog.