Does metformin cause vitamin B12 deficiency? Metformin is associated with lower vitamin B12 levels, and the American Diabetes Association's (ADA) Standards of Care in Diabetes—2026 suggest periodic B12 testing for people who take it long term. Most people on metformin do not become deficient, but the risk rises with time, and the symptoms can be easy to mistake for diabetes itself.
Key takeaways
- ADA's 2026 Standards say metformin is associated with vitamin B12 deficiency and suggest periodic testing, especially with anemia or nerve symptoms.
- In a long-term trial, low B12 was more common with metformin than with placebo after 5 years (4.3% vs 2.3%).
- The FDA label says metformin may interfere with B12 absorption and that the problem appears rapidly reversible with B12 supplementation or stopping the medicine.
- Never stop metformin on your own. A prescriber decides whether to test, treat, or change anything.
- Fatigue, numbness, and tingling can come from B12 deficiency, diabetic neuropathy, or other causes, so a blood test is how they are told apart.
Metformin and Vitamin B12: The Short Answer
- The link is well documented. ADA, the FDA prescribing information, and a long-term randomized trial all report lower B12 in people who take metformin.
- Risk grows with time on the medicine. The trial found higher odds of B12 deficiency for each added year of use.
- It is checkable and treatable. A blood test can find low B12, and the FDA label says the problem appears rapidly reversible with B12 supplementation or stopping metformin.
- It is not a reason to quit metformin. Metformin remains a widely used diabetes medicine. Questions about B12 belong with your prescriber or pharmacist.
What the Research Shows
The strongest long-term data come from the Diabetes Prevention Program Outcomes Study (DPPOS). It followed adults who had elevated blood sugar and extra weight and were randomly assigned to metformin or placebo, then followed many of them for years afterward. Researchers measured B12 at 5 years and at 13 years.
| Measure | Metformin group | Placebo group |
|---|---|---|
| Low B12 at 5 years | 4.3% | 2.3% |
| Low B12 at 13 years | 7.4% | 5.4% (difference not statistically significant) |
| Low or borderline-low B12 at 5 years | 19.1% | 9.5% |
| Low or borderline-low B12 at 13 years | 20.3% | 15.6% |
The authors also found that each additional year of metformin use was associated with higher odds of B12 deficiency (odds ratio 1.13). Anemia was more common in the metformin group, though it did not differ by B12 status, and nerve problems (neuropathy) were more common in people on metformin who also had low B12. The authors concluded that routine B12 testing in people treated with metformin should be considered.
The FDA prescribing information gives a similar picture. It says about 7% of people in 29-week clinical trials developed subnormal B12 levels, possibly because metformin interferes with B12 absorption, and that this may be associated with anemia. The label says people with inadequate B12 or calcium intake or absorption seem predisposed.
Our guide to how metformin works explains the medicine and its other side effects.
Symptoms of Low B12
The National Institutes of Health (NIH) Office of Dietary Supplements lists these signs of B12 deficiency:
- Tiredness or weakness
- Anemia (a low red blood cell count)
- A sore, inflamed tongue
- Palpitations
- Numbness or tingling in the hands or feet
NIH says nerve symptoms can occur without anemia, that symptoms can take years to appear, and that early diagnosis matters to avoid irreversible damage. ADA's Standards say metformin is associated with increased B12 deficiency risk and worsening neuropathy symptoms.
That overlap is the challenge. Numbness and tingling are also the signature of diabetic nerve damage, and tiredness has dozens of causes. Read about diabetic neuropathy, numbness in the hands, and feeling tired with diabetes. A blood test is how a clinician tells these apart, which is why you should not treat yourself based on symptoms alone.
Book a prompt appointment if you notice new numbness, tingling, unusual tiredness, palpitations, or a sore tongue, especially if you have taken metformin for years. Get emergency help for chest pain or trouble breathing.
Who Else Is at Risk for Low B12?
NIH names several other groups, and some overlap with people who take metformin:
- People who take acid-reducing medicines called proton pump inhibitors
- Adults over 50, since absorption can decline with age
- People with pernicious anemia or atrophic gastritis
- People who have had stomach or intestinal surgery
- Vegetarians and vegans, since plant foods contain no B12 unless fortified
If you fit more than one group, mention it to your prescriber. The combined picture matters more than any single factor.
How Testing Works
ADA's Standards suggest considering periodic B12 testing for people taking metformin, especially if anemia or peripheral neuropathy is present. The FDA label says to measure blood counts annually and to measure B12 at 2- to 3-year intervals. NIH advises asking a clinician about testing if you are at risk.
Your clinician decides how often to test you and what a result means. A "borderline" result is a good example: the trial counted both low and borderline-low levels, and what to do about a borderline number is a clinical judgment. Our guide to yearly diabetes tests shows where a B12 check can fit.
Food, Supplements, and Shots
NIH lists these B12 sources:
- Fish and shellfish, including clams and oysters
- Meat, poultry, and beef liver
- Eggs and dairy
- Fortified cereals and nutritional yeast
NIH says adults over 50 should get most of their B12 from fortified foods or supplements. It also says no form of B12 supplement is better than the others, that a prescription injection is used to treat deficiency, and that B12 has not been shown to cause harm even at high intakes but can interact with some medicines.
That does not mean everyone on metformin should start a supplement. ADA's Standards say supplements offer no benefit without an underlying deficiency, so the question to ask is whether you are low. Our overview of vitamins and supplements for diabetes explains how to handle supplements safely, including what to tell your pharmacist.
What to Do If You Take Metformin
- Keep taking it as prescribed. Do not stop, skip, or change your dose because of B12 concerns.
- Ask about a B12 test. Say how long you have taken metformin and mention any numbness, tingling, or tiredness.
- List every medicine and supplement. Acid reducers and other products affect the picture.
- Report new symptoms promptly. Early treatment protects nerves.
- Check your diet. If you eat little or no animal food, tell your clinician.
Frequently Asked Questions
Does metformin cause vitamin B12 deficiency?
Metformin is associated with vitamin B12 deficiency. ADA's 2026 Standards cite findings from the Diabetes Prevention Program Outcomes Study and suggest periodic B12 testing in people taking metformin long term. Most people on metformin do not become deficient, but the risk rises with years of use.
How common is low B12 with metformin?
In the Diabetes Prevention Program Outcomes Study, low B12 was found in 4.3% of the metformin group and 2.3% of the placebo group at 5 years. At 13 years the figures were 7.4% and 5.4%, a difference that was not statistically significant. The FDA label reports about 7% in 29-week trials.
What are the symptoms of low B12 from metformin?
NIH lists tiredness, anemia, a sore tongue, palpitations, and numbness or tingling. Nerve symptoms can occur without anemia and can take years to appear. Because diabetic neuropathy causes similar symptoms, a blood test is the way to tell the causes apart.
Should I take a B12 supplement if I take metformin?
Ask your prescriber first. ADA's Standards say supplements offer no benefit without an underlying deficiency, so a blood test comes first. If you are low, your clinician may recommend food changes, a supplement, or an injection.
How often should B12 be checked with metformin?
ADA suggests periodic testing, especially with anemia or nerve symptoms. The FDA label says to measure B12 at 2- to 3-year intervals. Your prescriber will set a schedule that fits your history and risk factors.
Can low B12 from metformin be reversed?
The FDA label says the problem appears rapidly reversible by stopping metformin or by B12 supplementation. Do not stop metformin on your own. NIH warns that nerve damage from long-standing deficiency can become irreversible, which is why early testing and treatment matter.
References
- American Diabetes Association Professional Practice Committee for Diabetes. "5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes—2026." Diabetes Care. 2026;49(Suppl. 1):S89–S131. Accessed October 2026.
- American Diabetes Association Professional Practice Committee for Diabetes. "9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2026." Diabetes Care. 2026;49(Suppl. 1). Accessed October 2026.
- Aroda VR, Edelstein SL, Goldberg RB, et al. "Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study." J Clin Endocrinol Metab. 2016;101(4):1754–1761.
- U.S. Food and Drug Administration. "Metformin hydrochloride extended-release oral solution prescribing information, Warnings and Precautions 5.2: Vitamin B12 Deficiency." Accessed October 2026.
- National Institutes of Health Office of Dietary Supplements. "Vitamin B12: Fact Sheet for Health Professionals." Updated July 2, 2025. Accessed October 2026.
- American Diabetes Association. "Diabetes, Vitamins & Supplements." Accessed October 2026.
Next Steps
If you take metformin, write down how long you have been on it, any numbness, tingling, or tiredness you have noticed, and your full medicine and supplement list. Ask your prescriber whether a vitamin B12 test is right for you.
For adults with type 2 diabetes or prediabetes who want lifestyle education alongside clinical care, the Done With Diabetes™ program, a holistic approach to diabetes type 2, organizes daily learning about meals, movement, sleep, and stress. It does not diagnose or treat B12 deficiency or diabetes, interpret test results, recommend supplements, change medicines, or replace your prescriber or care team.