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 first and often only medication they ever need. It’s cheap, effective, and has been used safely for decades. But behind its reputation as a reliable drug lies a quiet, growing problem: metformin can slowly drain your body of vitamin B12 - and many people don’t realize it until damage is already done.

How Metformin Steals Your B12

Metformin doesn’t cause B12 deficiency by killing cells or poisoning your gut. It interferes with how your body absorbs the vitamin. Vitamin B12 comes from food, binds to a protein called intrinsic factor, and then needs calcium to latch onto receptors in your small intestine. Metformin disrupts that calcium-dependent step. Without it, up to 30% of the B12 you eat just passes through your body unused.

This isn’t a rare side effect. It’s common. Studies show that for every extra gram of metformin you take daily, your risk of B12 deficiency jumps more than double. People on 2,000 mg or more per day - the standard high dose - are at the highest risk. And it doesn’t happen fast. Your liver stores about 2,500 micrograms of B12. You only need 2.4 micrograms a day. So it can take 5 to 10 years of daily metformin before your stores run low enough to cause symptoms.

That’s why so many people miss it. By the time they feel something wrong, they’ve been on the drug for years. And because the symptoms look like diabetes complications, doctors often blame high blood sugar instead of checking B12 levels.

Symptoms No One Tells You About

Vitamin B12 deficiency doesn’t just make you tired. It attacks your nerves. Early signs are easy to ignore: a sore tongue, mouth ulcers, or feeling unusually fatigued. But left unchecked, it can lead to permanent nerve damage.

Here’s what actually happens:

• Peripheral neuropathy - burning, tingling, or numbness in hands and feet. Often mistaken for diabetic neuropathy.
• Muscle weakness - you feel like you’re losing strength, even if you’re exercising.
• Balance problems - you stumble more, feel unsteady, or lose coordination.
• Memory issues or brain fog - confusion, trouble focusing, or mood changes.
• Vision problems - blurred vision or sensitivity to light.
• Pale or yellow skin - a sign your red blood cells are abnormal.

In extreme cases, untreated B12 deficiency causes subacute combined degeneration of the spinal cord - a rare but irreversible condition that damages the spinal cord’s ability to send signals. One Reddit user described a five-year journey of misdiagnoses before finally finding out his numb legs and walking trouble were from B12 deficiency, not worsening diabetes.

And here’s the kicker: you don’t need anemia to be deficient. Many people have low B12 with normal blood counts. That’s why just checking for anemia misses half the cases.

Who’s at Highest Risk?

Not everyone on metformin will develop B12 deficiency - but some groups are far more vulnerable:

• People taking metformin for more than 4-5 years
• Those on doses of 2,000 mg/day or higher
• Vegetarians and vegans - you already get less B12 from food, and metformin cuts absorption even more
• People using proton-pump inhibitors (PPIs) like omeprazole for heartburn - these drugs reduce stomach acid, which is needed to free B12 from food
• Older adults - your body naturally absorbs less B12 as you age
• People with Crohn’s disease, celiac disease, or other gut absorption issues

One study found that among metformin users on PPIs, over 40% developed B12 deficiency. That’s not coincidence - it’s a dangerous combo.

What Doctors Should Be Doing

In 2022, the UK’s Medicines and Healthcare products Regulatory Agency officially declared B12 deficiency a common side effect of metformin. That’s a big deal. It means this isn’t a theoretical risk anymore - it’s standard clinical knowledge.

But not all doctors are on the same page. The American Diabetes Association says to “consider” testing B12 levels in long-term users. The European Association for the Study of Diabetes says to test everyone on metformin every 2-3 years. The UK’s NICE guidelines are clearer: check B12 at least every 2-3 years, and annually if you’re in a high-risk group.

Here’s what good testing looks like:

• Serum B12 level - normal is above 221 pmol/L (some labs say 150, but levels below 221 often show symptoms)
• Methylmalonic acid (MMA) - if B12 is borderline, elevated MMA confirms tissue deficiency
• Homocysteine - also rises when B12 is low, though it can be affected by other factors

Don’t rely on just one number. A B12 level of 180 pmol/L might seem “normal” to some labs, but if you have nerve symptoms, it’s too low.

What to Do If You’re Deficient

Once deficiency is confirmed, treatment works fast - if you act early.

For mild to moderate deficiency, high-dose oral B12 (1,000-2,000 mcg daily) is just as effective as injections for most people. You can buy it over the counter. For severe deficiency or neurological symptoms, doctors often start with weekly injections of 1,000 mcg for 4 weeks, then switch to monthly.

One patient on the NHS forum shared that after 8 years on metformin, her B12 was 128 pmol/L - severely low. She started injections and within six months, her nerve pain improved dramatically. She still takes metformin, but now she takes B12 daily.

And here’s a surprising twist: calcium may help prevent it. A 2021 trial showed that taking 1,200 mg of calcium carbonate daily reduced B12 deficiency by 47% in metformin users. The theory? Calcium helps restore the absorption mechanism that metformin breaks. It’s not a cure, but it’s a simple, cheap way to lower risk.

What’s Changing in 2025?

The tide is turning. By 2025, routine B12 testing is expected to be standard in diabetes clinics worldwide. New guidelines from the American Diabetes Association now explicitly recommend checking B12 in anyone on metformin for more than 4 years.

Researchers are also exploring ways to redesign metformin. A new enteric-coated version is in trials - it releases the drug lower in the gut, where it interferes less with B12 absorption. Early results show 32% less B12 reduction over a year.

And genetics may play a role. Scientists have found people with certain variations in the CUBN gene - which controls the B12 receptor in the gut - are far more likely to develop deficiency on metformin. In the future, a simple genetic test could identify high-risk patients before they even start the drug.

What You Can Do Today

You don’t need to stop metformin. It’s still the best first-line treatment for most people with type 2 diabetes. But you do need to protect yourself.

Here’s your action plan:

1. If you’ve been on metformin for 4+ years, ask your doctor for a B12 blood test - don’t wait for symptoms.
2. If you’re vegetarian, vegan, or on PPIs, get tested even if you’ve only been on metformin for 2-3 years.
3. If your B12 is below 221 pmol/L, start supplementation. Oral 1,000-2,000 mcg daily is safe and effective.
4. Consider adding 1,200 mg of calcium carbonate daily - especially if you can’t take B12 supplements.
5. Track your symptoms. If you feel more tired, numb, or unsteady, get tested - even if your last B12 was “normal.”

This isn’t about fear. It’s about awareness. Metformin saves lives. But like all medicines, it has hidden costs. B12 deficiency is silent, slow, and reversible - if you catch it early. Waiting until your feet are numb or your memory is failing is too late.

Ask your doctor for a test. Take control. Your nerves - and your future - will thank you.