Metformin and Vitamin B12 Deficiency: What You Need to Know About Long-Term Risks

For millions of people with type 2 diabetes, metformin is the go-to medication. It’s affordable, effective, and has been used for decades. But there’s a quiet side effect that many patients - and even some doctors - don’t talk about enough: vitamin B12 deficiency. If you’ve been on metformin for more than four or five years, your body might be slowly running out of B12 - and the damage could be irreversible if you don’t catch it early.

How Metformin Drains Your B12

Metformin doesn’t just lower blood sugar. It also interferes with how your gut absorbs vitamin B12. The process happens in the lower part of your small intestine, called the ileum. Normally, B12 binds to a protein called intrinsic factor, and then latches onto receptors in the ileum with the help of calcium. Metformin blocks that calcium-dependent step. Without it, your body can’t absorb B12 properly.

Studies show this isn’t a rare glitch. It’s a direct, dose-related effect. For every extra 1 gram of metformin you take daily, your risk of B12 deficiency jumps by more than double. People taking 2,000 mg or more per day are at the highest risk. And it doesn’t happen overnight. Your liver stores about 2,500 micrograms of B12. You only need 2.4 micrograms a day. So it can take 5, 8, even 10 years before your levels drop low enough to cause symptoms.

Why This Is So Dangerous

Vitamin B12 isn’t just about energy. It’s critical for your nerves, brain, and blood. When you’re low, the first signs are subtle: feeling tired all the time, tingling in your hands or feet, trouble remembering things. These look exactly like symptoms of diabetic neuropathy - which is why so many people get misdiagnosed.

But here’s the scary part: if B12 deficiency isn’t treated, it can cause permanent nerve damage. One documented condition called subacute combined degeneration attacks the spinal cord. Patients describe walking like they’re drunk, losing balance, or even losing sensation in their legs. In some cases, the damage doesn’t reverse - even after years of B12 injections.

A 2016 study following over 3,000 people for 13 years found that each year on metformin increased the risk of B12 deficiency by 13%. And here’s what’s alarming: many of these people didn’t even have anemia. That means standard blood tests for anemia won’t catch it. You need a specific B12 blood test.

Who’s Most at Risk

Not everyone on metformin will get deficient. But certain groups are far more vulnerable:

• People taking metformin for 5+ years - risk climbs to 30% after 5 years, and over 50% after 12 years.
• Those on high doses - 2,000 mg or more daily.
• People using proton-pump inhibitors (PPIs) - drugs like omeprazole for heartburn. These reduce stomach acid, which is needed to pull B12 out of food. Combine that with metformin, and your risk jumps by nearly 40%.
• Vegans and vegetarians - if you don’t eat meat, eggs, or dairy, your dietary B12 intake is already low. Metformin makes it worse.
• Older adults - natural B12 absorption declines with age, and metformin accelerates it.

One patient on a UK diabetes forum shared that after 8 years on metformin, she was told her numb feet were just "worsening diabetes." Her B12 level was 128 pmol/L - far below the normal range of 221+. After six months of injections, her symptoms improved dramatically. She wasn’t alone.

What Symptoms to Watch For

Don’t wait for numbness or weakness. Early signs are easy to miss:

• Constant fatigue - reported by 72% of deficient patients in long-term studies
• Muscle weakness or difficulty climbing stairs
• Sore, red tongue or mouth ulcers
• Pale or slightly yellow skin
• Blurred or double vision
• Memory lapses or brain fog
• Feeling unsteady on your feet

If you’ve been on metformin for more than four years and notice any of these, get tested. Don’t assume it’s just your diabetes acting up.

How to Test and What to Do

The best way to catch B12 deficiency early is with a simple blood test. But here’s the catch: serum B12 alone isn’t always enough. Some people have "normal" B12 levels but still have tissue deficiency. That’s where two other markers help:

• Methylmalonic acid (MMA) - rises when your cells are starved of B12
• Homocysteine - also increases with B12 deficiency

Experts now recommend testing B12 at baseline (when you start metformin) and then every 2-3 years. If you’re in a high-risk group - like a vegetarian, on PPIs, or over 65 - test annually.

Once deficiency is confirmed, treatment is straightforward:

• High-dose oral B12 - 1,000 to 2,000 mcg daily. Surprisingly, this works almost as well as injections for most people.
• Injections - 1,000 mcg weekly for 4 weeks, then monthly. Used for severe deficiency or neurological symptoms.

In one study, 89% of patients saw their blood counts improve within 3 months of starting treatment. Nerve symptoms took longer - sometimes up to a year - but many improved significantly.

A Simple Way to Prevent It

Here’s something surprising: taking calcium supplements might help. A 2021 trial showed that people who took 1,200 mg of calcium carbonate daily while on metformin had a 47% lower chance of developing B12 deficiency. Why? Calcium helps restore the absorption pathway that metformin blocks.

You don’t need fancy pills. A regular over-the-counter calcium tablet (like calcium carbonate) taken with your evening metformin dose can make a real difference. Talk to your doctor about adding it - especially if you’re not ready to stop metformin.

What the Experts Are Saying Now

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) updated its guidance in 2022, calling B12 deficiency a "common side effect" of metformin. The European Association for the Study of Diabetes says testing should be routine. The American Diabetes Association says you should "consider" testing - but many specialists now say that’s not enough.

Professor John Wilding, who led the landmark UKPDS study, says: "Neurological damage from untreated B12 deficiency in diabetics on metformin can be permanent - and it’s often mistaken for diabetic nerve damage. We’re missing this because we’re not looking for it."

The National Institute for Health and Care Excellence (NICE) now lists metformin as a major risk factor in its official guidelines. If you’re on metformin long-term, your doctor should be checking your B12 - even if you feel fine.

What’s Next?

Researchers are working on better solutions. One new version of metformin, called enteric-coated, is designed to release the drug lower in the gut - away from the B12 absorption zone. Early trials show it reduces B12 loss by 32% compared to regular metformin. But it’s not widely available yet.

Another promising area is genetics. Scientists have found that some people have a gene variation (in the CUBN gene) that makes them more likely to absorb less B12 when taking metformin. In the future, a simple genetic test might tell you if you’re at higher risk before you even start the drug.

For now, the best defense is simple: know your risk. Get tested. Don’t wait for symptoms. And if you’re on metformin for more than four years, ask your doctor: "Have you checked my B12 lately?"

What to Do Next

If you’re on metformin and haven’t had your B12 checked in the last two years, book a blood test. Ask for serum B12, MMA, and homocysteine if your level is borderline. If you’re vegetarian, on PPIs, or over 65, don’t wait - get tested now.

Don’t ignore fatigue, tingling, or memory issues. They might not be "just diabetes." They could be your body screaming for B12. And if your doctor says it’s not necessary, ask them to check the latest NICE and ADA guidelines. You have the right to know.

Metformin saves lives. But like all medicines, it comes with trade-offs. The good news? This one is easy to fix - if you catch it early.