Why Should Metformin Users Watch Their Vitamin B12?

Vitamin B12 deficiency can lead to cognitive impairment and dementia as well as fatigue and nerve damage. Studies have shown that one of the most common diabetes medications, metformin, can increase the risk of this nutritional deficiency.

How Scientists Studied Metformin’s Effect:

In one study, over 3,000 adults at high risk for type 2 diabetes were enrolled in the Diabetes Prevention Program (Journal of Clinical Endocrinology and Metabolism, April 2016). They were randomized to receive metformin or placebo.

Blood samples taken at five and 13 years after the start of the study showed that average vitamin B12 levels were lower among participants on metformin at the five-year mark. More alarming, vitamin B12 deficiency was twice as common among those taking metformin. Approximately 4 percent of the metformin users were deficient, compared to 2 percent of those on placebo. 20 percent of those on metformin had borderline low levels of this vitamin. Similar trends were seen at year 13.

Our Advice to Metformin Users:

People who are taking metformin should have their vitamin B12 levels monitored regularly. We don’t think people should refuse to take metformin because of this potential complication. It has a number of very useful benefits, including weight control and cancer prevention. But it definitely makes sense for metformin users to be on the lookout for this problem.

Does Sublingual Vitamin B12 Overcome the Metformin Effect?

Q. You have written about the importance of vitamin B12 and medications, like metformin, that might interfere with it. Older adults (over 50) can lose the ability to absorb B12, even with a diet high in foods that have a lot.

Lack of absorption means that even supplementing can fail to solve the problem. In that case, using sublingual (under the tongue) B12 tablets can work well, since this allows the vitamin to be absorbed directly into the bloodstream via the mucus membranes of the mouth. Research has shown that this approach works as well as injections and is far more convenient and consistent.

Sublingual B12 changed my life. It didn’t take too long for the confusion and other symptoms to abate. I’m a fan.

A. Suboptimal levels of vitamin B12 can lead to nerve pain, weakness, unsteadiness, depression and confusion, among other problems. That’s why we stress the importance of checking vitamin B12 levels for people taking an acid-suppressing drugs such as omeprazole or esomeprazole. Like metformin, these can deplete vitamin B12 over time.

You are correct that sublingual administration of vitamin B12 is effective. An Israeli study found it raised vitamin B12 levels even better than intramuscular injection of the vitamin (Drug Delivery and Translational Research, June 2019). A systematic review concluded that it doesn’t much matter how you get your vitamin B12, so long as you get enough (Irish Journal of Medical Science, June 2024).

Other Drugs That Affect Vitamin B12:

Metformin users may also take other medicines that can decrease vitamin B12 levels.

Q. I have been taking metformin for type 2 diabetes. It gives me gas and a bellyache.

As a result, I have also been taking omeprazole for a long time. When I realized that these drugs could deplete vitamin B12, I began taking a supplement. The tingling and nerve pain have improved a lot.

I wonder how many people know that metformin can affect nerves through its impact on vitamin B12. They may be going through life with more pain than need be. My own doctor never mentioned that my medications could reduce vitamin B12 and I was never tested.

PPIs Can Mess with Vitamin B12:

A. The diabetes drug metformin and all the proton pump inhibitors (PPIs) such as omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid) and pantoprazole (Protonix) can interfere with vitamin B12 absorption. When levels of this crucial vitamin drop too low, the symptoms may include numbness and tingling in the hands and feet as well as weakness, fatigue, constipation and loss of appetite. People with too little vitamin B12 may also feel depressed, confused or unsteady. In some cases, memory deteriorates to the point that they might be misdiagnosed with dementia.

We commend you for being alert to the potential side effects of your medications. Taking a supplement is a good way to deal with vitamin depletion caused by such medications. In many instances, a high-dose oral vitamin B12 supplement, such as 1,000 mcg (1 mg), provides enough of this vitamin that injections are not necessary.

Treating Diabetes:

Metformin is a good treatment for diabetes. There are other options for controlling blood sugar, however. You can learn more about them in our Guide to Managing Diabetes.