A large study of over 14,000 people with type 2 diabetes found that those taking metformin for 4 or more years had a higher risk of vitamin B12 deficiency compared to those taking it for shorter periods or not at all. Vitamin B12 is important for nerve health, and the study also found that long-term metformin users had more nerve problems in their hands and feet. Doctors may need to check vitamin B12 levels more often in patients who have been on metformin for many years to prevent these complications.

The Quick Take

  • What they studied: Whether taking metformin (a common diabetes medicine) for a long time increases the chances of having low vitamin B12 and nerve damage in the feet and hands
  • Who participated: 14,808 adults with type 2 diabetes, with 9,136 taking metformin. Of those on metformin, 5,609 had been taking it for 4 years or longer
  • Key finding: People taking metformin for 4+ years were 67% more likely to have low vitamin B12 than those not taking metformin, and 39% more likely to have nerve problems compared to those taking it for less than 4 years
  • What it means for you: If you’ve been taking metformin for several years, ask your doctor to check your vitamin B12 levels regularly. Low B12 can cause nerve problems, so catching it early matters. This doesn’t mean you should stop taking metformin—it’s still an important diabetes medicine—but monitoring is important

The Research Details

Researchers looked at health records from a large database called All of Us, which contains medical information from thousands of Americans. They compared three groups: people taking metformin for 4 years or longer, people taking it for less than 4 years, and people not taking metformin at all. They looked at how many people in each group had low vitamin B12 and nerve problems. The researchers adjusted their analysis to account for other factors that might affect these outcomes, like age, weight, and other medicines people were taking.

This type of study is useful because it looks at real-world health records rather than controlled lab experiments. It shows patterns that actually happen in people’s lives over time. However, because it’s observational (just looking at what happened, not testing something new), we can see connections but can’t prove that metformin directly causes the problem.

The study included a very large number of people (over 14,000), which makes the findings more reliable. The researchers adjusted for many other factors that could affect the results. However, this was a snapshot study looking at data from one point in time, so we can’t be completely certain about cause and effect. The findings are strong enough that doctors should pay attention, but more research is needed to fully understand the relationship.

What the Results Show

Among people taking metformin for 4 years or longer, vitamin B12 deficiency was significantly more common. Specifically, long-term users were 67% more likely to have low B12 compared to people not taking metformin, and 38% more likely compared to those taking it for less than 4 years. These differences were very unlikely to happen by chance (p < 0.001). Nerve problems in the feet and hands were also more common in long-term metformin users—39% higher than in short-term users. Interestingly, long-term users didn’t have significantly more nerve problems than people not taking metformin at all, which suggests that low vitamin B12 might be part of the explanation for the nerve issues.

The study also looked at how the length of time since diabetes diagnosis affected these relationships. The findings suggest that the longer someone takes metformin, the more important it becomes to monitor vitamin B12 levels. The connection between low B12 and nerve problems was particularly clear in long-term users, supporting the idea that B12 deficiency may be contributing to nerve damage.

Previous research has suggested that metformin can interfere with vitamin B12 absorption in the stomach, but this is one of the largest studies to look at the real-world impact of this effect. The findings confirm what smaller studies have suggested and show that this is a meaningful problem affecting a significant number of people taking this common diabetes medicine.

This study looked at data from one point in time rather than following people over years, so we can’t be completely certain about cause and effect. The study couldn’t prove that metformin directly causes low B12—only that the two are connected. Some people in the database may not have had their B12 or nerve problems checked, which could affect the results. Additionally, the study couldn’t account for all possible factors that might influence B12 levels, such as diet or other supplements people were taking.

The Bottom Line

If you’ve been taking metformin for 4 years or longer, talk to your doctor about checking your vitamin B12 levels regularly (moderate confidence). Ask about B12 supplements if your levels are low. Don’t stop taking metformin without talking to your doctor first, as it’s an important diabetes medicine. Consider eating more B12-rich foods like meat, fish, eggs, and dairy products, or ask about B12 supplements (moderate confidence).

This is most important for people with type 2 diabetes who have been taking metformin for 4 years or longer. It’s also relevant for doctors prescribing metformin long-term. People taking metformin for less than 4 years should still be aware but may have lower risk. People not taking metformin don’t need to worry about this particular issue.

Vitamin B12 deficiency develops slowly over time, so the risk increases the longer you take metformin. It may take months or years to develop noticeable symptoms. If you start taking B12 supplements or increase B12 intake, it may take several weeks to months to feel improvements in energy or nerve symptoms.

Want to Apply This Research?

  • Set a quarterly reminder to log your B12 levels if you’ve been on metformin for 4+ years. Track the date and result (normal, low, or supplementing) to share with your doctor and monitor trends over time
  • If you’re a long-term metformin user, add a weekly reminder to eat B12-rich foods (eggs, cheese, fish, chicken) or take a B12 supplement as recommended by your doctor. Log which B12 sources you’re using to stay consistent
  • Create a health dashboard showing your metformin duration, B12 check-up dates, and any nerve symptoms (tingling, numbness). Review quarterly with your doctor to catch any changes early and adjust supplementation if needed

This research shows an association between long-term metformin use and vitamin B12 deficiency, but does not prove that metformin causes this problem. If you take metformin, do not stop taking it without talking to your doctor first. Always consult with your healthcare provider before making changes to your diabetes medication or starting supplements. This information is for educational purposes and should not replace professional medical advice. Individual results may vary based on your specific health situation.