Metformin is one of the most widely dispensed oral diabetes medications for good reason. It works great, lowering A1c 1-2% points, with an added benefit of dropping LDL cholesterol levels. It doesn’t cause hypoglycemia or weight gain and it is incredibly cheap. Many pharmacies offer a 3 month supply of this highly effective glucose-lowering medication for $10 or less, and that’s without insurance. This medication also seems to boost the diversity of the gut microbiota, in particularly increased levels of the very beneficial Akkermansia muciniphila.

However, it does have a few drawbacks. A small group of people on metformin will experience a B₁₂ deficiency. This B₁₂ deficiency may manifest as neuropathic pain or anemia.

Plus, a percentage of people will experience upset stomach, bloating, and diarrhea. People with these complaints will often respond better to the extended-release version (metformin XR), which isn’t any more expensive and it can be taken once a day. See our Mediation PocketCards for more info.

How prevalent is B₁₂ Deficiency with metformin?

Currently, the ADA Standards have no clear recommendation for checking B₁₂ for those on metformin, but it does note that long-term metformin use is associated with B₁₂ deficiencies and that “measuring B₁₂ levels should be considered for those with type 1 diabetes, peripheral neuropathy or unexplained anemia”.

To add to this, a study published this month in Human Nutrition and Metabolism, found the prevalence of B₁₂ deficiency appears to be about 17% in people on metformin therapy. The highest rates of B₁₂ deficiency were seen in those taking metformin for 2 years. Moreover, vitamin B₁₂ deficiency is influenced by the occurrence and duration of diabetes.

They also measured the intake of vitamin B₁₂ in the daily diet of the study participants. Those with lower vitamin B₁₂ blood levels were also consuming less foods rich in vitamin B₁₂ in their daily meal plan.

Recommendations for Regular B₁₂ Monitoring and Replacement

The authors of this article suggest that routine monitoring for vitamin B₁₂ serum levels is needed in people with T2DM, particularly when metformin is used for more than 2 years with a dose of over 1000 mg per day. They also recommend further studies are needed to assess the correlation between metformin duration and dose and patients with T2DM and other metabolic syndromes.

B₁₂ replacement therapy

This article, nor the ADA Standards recommend dosing for B₁₂ replacement therapy. However, based on several articles, including this 2005 Cochrane review, high-dose oral replacement (1 mg to 2 mg per day) for B₁₂ deficiency, seems to be as effective as parenteral B₁₂ administration for correcting anemia and neurologic symptoms.

Conclusion – Vitamin B₁₂ deficiency is associated with worsening nerve pain and anemia. Testing B₁₂ levels for those on long-term metformin therapy, especially for those taking more than 1000 mg of metformin a day seems like a reasonable approach. Increasing the intake of foods high in vitamin B₁₂ and providing oral B₁₂ replacement therapy of 1 mg to 2 mg a day, are both helpful interventions to boost B₁₂ levels.

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