Metformin has been a cornerstone of type 2 diabetes treatment for decades. It is effective, inexpensive, and has a long safety record. Most patients are told to watch their blood sugar, get regular A1C checks, and take it with food to reduce stomach upset. What most are not told, until they develop symptoms, is that metformin can deplete vitamin B12 in a clinically significant way.
This is not obscure pharmacology. The UK's Medicines and Healthcare products Regulatory Agency updated the Glucophage (metformin) prescribing information to classify vitamin B12 deficiency as a common adverse effect. "Common" in regulatory language means it affects more than 1 in 10 patients who take it.
The Primary Concern: Vitamin B12
Studies have shown that metformin is associated with vitamin B12 deficiency in up to 30 percent of patients taking it long term. The mechanism is well understood: metformin interferes with the absorption of the B12 intrinsic factor complex in the small intestine, reducing how much vitamin B12 the body can pull from food.
This matters because vitamin B12 deficiency is not benign. It causes:
- Peripheral neuropathy, tingling, numbness, or burning in the hands and feet (symptoms that can look a lot like diabetic neuropathy, making it easy to miss the B12 component)
- Megaloblastic anemia, large, malformed red blood cells that do not function properly
- Cognitive decline, memory problems, difficulty concentrating, fatigue
- Elevated homocysteine, an independent cardiovascular risk factor
The compounding problem is that the symptoms of B12 deficiency overlap significantly with complications of diabetes itself. A patient who develops peripheral neuropathy while on metformin may have their neuropathy attributed entirely to their diabetes when B12 deficiency is the actual or contributing cause.
Who Is Most at Risk
The risk of B12 depletion from metformin is dose- and duration dependent. Higher doses and longer treatment duration increase risk. Additional risk factors include:
- Vegetarian or vegan diet (dietary B12 comes almost entirely from animal products)
- Age over 65 (B12 absorption declines with age regardless of metformin)
- History of gastritis or use of proton pump inhibitors (PPIs), which also reduce B12 absorption
- Individuals with pre existing B12 levels on the lower end of normal
The American Diabetes Association Recommendation
The ADA recommends periodic monitoring of vitamin B12 levels in patients on metformin, especially those with peripheral neuropathy or other symptoms. GoodRx and other clinical references suggest this check should happen at least once a year for patients on long term metformin.
If your B12 is low, your prescriber will determine whether oral supplements or intramuscular B12 injections are the right correction based on how severe the deficiency is and whether you have absorption issues.
Secondary Depletions: Folate and CoQ10
Metformin has also been associated with depletion of folic acid and, to a lesser degree, CoQ10.
Folate (vitamin B9): Some research suggests metformin may also reduce folate levels. This is particularly relevant for women of childbearing age on metformin for conditions like PCOS. A daily multivitamin with adequate folate, or a prenatal vitamin for those trying to conceive, addresses this concern.
CoQ10: The evidence for metformin depleting CoQ10 is weaker than for B12, but CoQ10 supplementation may be worth discussing with your provider, particularly if you are also on a statin (which depletes CoQ10 through a separate mechanism).
What to Do About It
The practical steps are straightforward:
- Ask your prescriber to check your vitamin B12 level at least once a year while on metformin. If you haven't had it checked recently, bring it up at your next appointment.
- Increase dietary B12 sources where possible, beef, fish, eggs, dairy, and fortified foods are good sources.
- Don't automatically start a B12 supplement without guidance. GoodRx's pharmacist guidance specifically notes that supplementation is warranted when levels are actually low, not as a precaution for everyone on metformin. Let your lab results and prescriber guide that decision.
- Take a daily multivitamin containing the RDA for B12 and folate if your prescriber agrees it is appropriate for your situation.
When to Talk to a Pharmacist
Worth a conversation if:
- You have been on metformin for more than one year and have not had your B12 checked
- You are experiencing tingling, numbness, fatigue, or memory changes while on metformin
- You are a vegetarian or vegan taking metformin
- You are a woman of childbearing age on metformin for PCOS and are considering pregnancy
- You are also taking a proton pump inhibitor and want to understand combined depletion risk
You can shop pharmacist selected supplements including B12 and B complex formulations at Fairview Pharmacy.
This article is for general information only and is not a substitute for personalized medical advice. Before starting or changing any medication, including over the counter products and supplements, talk with your pharmacist or physician about your specific situation.