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

For over 25 years, metformin has been the go-to drug for managing type 2 diabetes. It’s cheap, effective, and generally safe. But behind its widespread use is a quiet, often overlooked risk: vitamin B12 deficiency. And it’s not rare. It’s common. And if left unchecked, it can lead to nerve damage, fatigue, and even irreversible neurological problems - all masked as worsening diabetes symptoms.

How Metformin Drains Your B12

Metformin doesn’t just lower blood sugar. It also interferes with how your body absorbs vitamin B12 in the small intestine. The drug blocks calcium-dependent receptors in the ileum - the final part of your small intestine - where B12 normally binds to a protein called intrinsic factor and gets pulled into your bloodstream. Without enough calcium to help this process, up to 30% less B12 gets absorbed. It’s not a mystery; it’s a known mechanism backed by multiple studies.

And it gets worse with time. The longer you take metformin, the more your body’s B12 stores drop. You start with about 2,500 micrograms stored in your liver. You only need 2.4 micrograms a day. So it takes years for symptoms to show up. That’s why most people don’t realize they’re deficient until they’ve been on metformin for five, eight, or even ten years.

It’s not just the dose - though higher doses (2,000 mg/day or more) raise the risk - but the duration. A landmark 13-year study from the Diabetes Prevention Program found that each year of metformin use increased the chance of B12 deficiency by 13%. By year 10, nearly half of long-term users had levels low enough to cause problems.

Who’s Most at Risk?

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

• People taking 2,000 mg or more daily - Risk jumps significantly above this threshold.
• Those on metformin for 4+ years - Deficiency rarely shows up before this point.
• Vegetarians and vegans - If you don’t eat meat, eggs, or dairy, you’re already getting less B12 from food. Metformin makes it worse.
• People on proton-pump inhibitors (PPIs) - Drugs like omeprazole (Prilosec) reduce stomach acid, which is needed to free B12 from food. Add metformin, and absorption drops even further. Studies show up to 40% of diabetics on PPIs also develop B12 deficiency.
• Older adults - Natural B12 absorption declines with age. Metformin accelerates it.

One study found that patients with all four risk factors - high-dose metformin, PPI use, vegetarian diet, and age over 65 - had a 52% chance of being deficient after 12 years.

Symptoms That Get Mistaken for Diabetes

This is the dangerous part. B12 deficiency doesn’t always cause anemia. In fact, in over a third of cases, neurological symptoms appear first - and they look exactly like diabetic nerve damage.

Common signs include:

• Constant fatigue - reported by 72% of deficient patients in long-term studies
• Tingling or numbness in hands and feet - often blamed on diabetic neuropathy
• Muscle weakness - especially in legs, making walking harder
• Sore, red tongue or mouth ulcers
• Blurred or double vision
• Pale or yellowish skin
• Memory problems or brain fog

One patient on Reddit, u/MetforminSurvivor, spent five years being told his numb feet were just "worsening diabetes." Only after his B12 level hit 142 pmol/L (normal is above 221) did he get diagnosed with subacute combined degeneration - a serious spinal cord injury caused by long-term B12 lack. Some damage was permanent.

Another patient, "DiabeticSince2008," shared on NHS forums that after eight years on metformin, he was so weak he could barely climb stairs. His doctor finally tested his B12 - it was 128 pmol/L. After six months of injections, his energy returned. His nerve pain improved. He wasn’t getting worse from diabetes. He was just deficient.

Why Doctors Miss It

Many doctors still think B12 deficiency only shows up with anemia - pale skin, fatigue, fast heartbeat. But in metformin users, neurological damage often comes before any blood changes. A 2023 review found that 38% of patients had nerve symptoms before their blood tests showed low B12.

Also, standard B12 blood tests aren’t perfect. A level between 200 and 300 pmol/L might be "normal" on paper, but still too low for your nerves. That’s why experts now recommend checking methylmalonic acid (MMA) and homocysteine levels too. When B12 is low, MMA rises - even if your B12 number looks okay. It’s a more accurate signal of what’s happening in your tissues.

What You Should Do

If you’ve been on metformin for four or more years, here’s what you need to do:

1. Ask your doctor for a B12 blood test - don’t wait for symptoms.
2. Request MMA and homocysteine tests if your B12 is borderline (between 200-350 pmol/L).
3. Get tested every 2-3 years - or annually if you’re vegetarian, on PPIs, or over 65.
4. Consider calcium supplements - taking 1,200 mg of calcium carbonate daily has been shown to reduce B12 deficiency risk by 47% in metformin users.
5. Don’t stop metformin - it’s still the best drug for most people with type 2 diabetes. Fix the deficiency, not the medication.

Treatment: Simple, Fast, Effective

Once you’re diagnosed, fixing it is straightforward.

For mild to moderate deficiency (B12 150-300 pmol/L):

• Take 1,000-2,000 mcg of oral B12 daily
• Results usually show in 4-8 weeks: energy improves, tingling fades

For severe deficiency (below 150 pmol/L) or neurological symptoms:

• 1,000 mcg injections once a week for 4 weeks
• Then monthly for life, or switch to high-dose oral if absorption improves

Studies show 89% of patients recover fully with treatment - but only if caught early. Delayed treatment can lead to permanent nerve damage.

The Bigger Picture

With over 150 million people worldwide taking metformin, even a 10-20% deficiency rate means millions are at risk. The UK’s NHS spends £47 million a year treating complications from undiagnosed B12 deficiency in metformin users. That’s preventable money - and preventable suffering.

Regulators are catching on. The FDA updated metformin’s label in 2022. The European Medicines Agency added B12 deficiency as a known side effect in 2021. NICE (UK) and the European Association for the Study of Diabetes now recommend routine testing. The American Diabetes Association says testing should be "considered" - but many experts argue that’s not enough.

Future solutions are coming. Researchers are testing enteric-coated metformin - a version that releases the drug lower in the gut, where it doesn’t interfere with B12 absorption. Early trials show 32% less B12 loss. Genetic testing may soon identify people with mutations in the cubilin gene - making them extra sensitive to metformin’s effect on B12.

For now, though, the solution is simple: test, treat, and monitor. You don’t need to stop metformin. You just need to know your B12 level.

What to Ask Your Doctor

Don’t wait for symptoms. If you’ve been on metformin for four or more years, ask these questions:

• "Have you checked my vitamin B12 level?"
• "Can we also test my methylmalonic acid (MMA) and homocysteine?"
• "Should I take calcium supplements with my metformin?"
• "How often should I get tested?"
• "If my B12 is low, what’s the best treatment for me - pills or shots?"

These aren’t niche questions. They’re essential. Your doctor should know the answer.