Metformin is a popular medicine that helps millions of people manage type 2 diabetes, but scientists have discovered it can cause vitamin B12 and folate deficiencies over time. This review examines why this happens by looking at recent research. The problem might involve how your body absorbs these vitamins, changes in your gut bacteria, or how your body stores these nutrients. Understanding these mechanisms could help doctors prevent or treat this side effect better in the future.

The Quick Take

  • What they studied: Why does metformin, a common diabetes medicine, cause some people to develop low levels of vitamin B12 and folate?
  • Who participated: This is a review article that examined many previous studies about metformin users, rather than a new study with participants
  • Key finding: Scientists found multiple reasons why metformin causes these deficiencies: problems with how your body absorbs these vitamins, changes in gut bacteria that compete for B12, and how your body redistributes these nutrients
  • What it means for you: If you take metformin long-term, your doctor should monitor your B12 and folate levels. Taking calcium supplements or certain other medicines may help prevent these deficiencies, though more research is needed

The Research Details

This is a review article, meaning researchers searched through many published studies to understand what scientists already know about metformin and vitamin deficiencies. They looked at studies in two major scientific databases (PubMed and SCOPUS) using specific search terms related to metformin, B12, and folate. Rather than doing their own experiment, they analyzed and summarized findings from other researchers’ work to create a comprehensive picture of the problem.

A review article is valuable because it brings together all the available research on a topic, helping doctors and scientists understand the big picture. Since metformin is used by millions of people worldwide, understanding why it causes these deficiencies is important for improving patient care and preventing serious health problems.

This review was published in a peer-reviewed medical journal, meaning other experts checked the work. However, as a review article, it summarizes other studies rather than providing new experimental data. The strength of the conclusions depends on the quality of the studies reviewed. The researchers acknowledged that the exact mechanisms aren’t fully understood yet, which shows scientific honesty about current knowledge gaps.

What the Results Show

Early research focused on how metformin interferes with a special protein called intrinsic factor that helps your body absorb vitamin B12 from food. Scientists also found that metformin affects certain enzymes in your intestines that are needed for vitamin absorption. Some people developed temporary deficiencies that went away, while others had persistent problems that lasted longer. Recent studies suggest that bacteria in your gut may play a bigger role than previously thought. These bacteria can actually capture and use vitamin B12 that your body needs, competing with you for this essential nutrient. Some research also found that metformin might cause your body to redistribute B12 without actually losing it, though this doesn’t fully explain all cases of deficiency.

The review identified that calcium supplements and a medicine called miglitol show promise in helping prevent or reduce these deficiencies in people taking metformin. However, more research is needed to confirm how effective these approaches are and how they work. The deficiencies appear to develop gradually over time with long-term metformin use, rather than happening immediately.

This review builds on decades of research about metformin’s side effects. Earlier studies focused mainly on absorption problems in the intestines, but newer research has shifted focus to the role of gut bacteria and how the body handles and stores these vitamins. The review shows that scientists’ understanding has evolved from simple explanations to more complex ones involving multiple body systems.

The researchers noted that the exact mechanisms causing these deficiencies haven’t been completely figured out yet. Different studies sometimes found different causes, suggesting the problem may work differently in different people. Most research has been done in laboratory settings or small groups, so we need larger studies in real patients to confirm findings. The review also couldn’t determine how common these deficiencies are across all metformin users or predict who is most at risk.

The Bottom Line

People taking metformin long-term should have their B12 and folate levels checked regularly by their doctor (moderate confidence). If deficiencies develop, taking calcium supplements or discussing alternative medicines with your doctor may help (low to moderate confidence, needs more research). Don’t stop taking metformin without talking to your doctor, as it’s an important diabetes medicine (high confidence).

Anyone taking metformin for type 2 diabetes, especially those on it for many years, should be aware of this potential side effect. Older adults, people with digestive problems, and vegetarians (who get B12 mainly from supplements) may be at higher risk. People without diabetes taking metformin for other reasons should also discuss this with their doctor.

Deficiencies typically develop gradually over months to years of metformin use, not immediately. Regular blood tests can catch problems early before symptoms develop. If you start supplements or make changes, it may take several weeks to months to see improvements in blood levels.

Want to Apply This Research?

  • Log your metformin doses and set reminders for B12/folate blood tests every 6-12 months. Track any symptoms like fatigue, numbness, or weakness that might indicate deficiency
  • Set a reminder to discuss B12 and folate screening with your doctor at your next appointment. If recommended, add a B12 or folate supplement to your daily routine and log it in the app alongside your metformin
  • Create a health timeline showing metformin start date and all B12/folate test results. Track energy levels and any neurological symptoms monthly to catch problems early. Share this data with your doctor to personalize your care

This review summarizes scientific research about metformin and vitamin deficiencies but is not medical advice. If you take metformin, consult your doctor about whether B12 and folate screening is appropriate for you. Do not stop taking metformin or start supplements without discussing it with your healthcare provider first. This information is for educational purposes and should not replace professional medical evaluation and treatment.