Metformin tied to risk of B12 deficiency- Study

People taking metformin, a common type 2 diabetes medication, for several years may be at heightened risk of vitamin B12 deficiency and anemia, according to a new analysis of long-term data.

Metformin helps to control the amount of sugar, or glucose, in the blood by reducing how much glucose is absorbed from food and produced by the liver, and by increasing the body’s response to the hormone insulin, according to the National Institutes of Health.

“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),” said senior study author Dr. Jill P Crandall of Albert Einstein College of Medicine in New York City, by email.

“Smaller numbers of people take metformin for prevention of diabetes or treatment of polycystic ovary syndrome,” Crandall told Reuters Health.

The researchers used data from the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study, which followed participants at high risk for type 2 diabetes for more than 10 years.

The study began with more than 3,000 people age 25 years and older with high blood sugar. The participants were randomly assigned to receive either 850 milligrams of metformin twice daily, placebo medication or an intensive lifestyle program than did not include medication. For the new analysis only those taking placebo or metformin were considered, and about 50 participants were excluded after having weight-loss surgery, which would affect their diabetes outcomes.

During follow-up, the participants provided blood samples at the five- and 13-year points.

Using these blood samples, the researchers found that at year five, average B12 levels were lower in the metformin group than the placebo group, and B12 deficiency was more common, affecting 4 percent of those on metformin compared to 2 percent of those not taking the drug.

Borderline low B12 levels affected almost 20 percent of those on metformin and 10 percent of those taking placebo.

Average vitamin B12 levels were higher by year 13 than in year five, but B12 deficiency was also more common in both the metformin and placebo groups, as reported in the Journal of Clinical Endocrinology and Metabolism.

Vitamin B12 deficiency may lead to nerve damage which can be severe and may be irreversible, Crandall said.

“Severe and prolonged B12 deficiency has also been linked to impaired cognition and dementia,” she said. “It can also cause anemia (low red blood cell count) - fortunately, this condition is reversible with treatment.”

More people in the metformin group were also anemic at year five than in the placebo group.

There are more than three million cases of vitamin B12 deficiency each year in the U.S., which can be caused by diet or certain medical conditions. Symptoms include fatigue, and numbness or tingling.

Humans do not make vitamin B12 and need to consume it from animal sources or supplements. Vegetarians may get enough from eating eggs and dairy products, but vegans need to rely on supplements or fortified grains.

Doctors who prescribe metformin to patients long-term for type 2 diabetes, gestational diabetes, polycystic ovarian syndrome or other indications should consider routine measurement of vitamin B12 levels, the authors conclude.

“The FDA and organizations such as the American Diabetes Association do not have any formal recommendations for B12 monitoring for people taking metformin,” Crandall said. “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,” she said.

Restoring healthy B12 levels is easy to accomplish with pills or monthly injections, she added.

“The risk of B12 deficiency should not be considered a reason to avoid taking metformin,” Crandall said.

Source: Reuters