Pharmacists Can Develop More Effective Consults for Older Patients About Metformin and Vitamin B12 Deficiency

Pharmacists Can Develop More Effective Consults for Older Patients About Metformin and Vitamin B12 Deficiency

Metformin and Vitamin B12 DeficiencyManaging type 2 diabetes can be quite a challenge for older patients, so it doesn’t help that the preferred treatment—metformin—could add to the problem by causing a deficiency of vitamin B12. Low B12 leads to a higher risk of falls and nerve damage that mimics diabetic neuropathy.

Pharmacist counseling may be the first—or the only—time that elderly patients learn about the relationship between metformin and vitamin B12 deficiency, so it’s vital information to convey when you dispense medications. Your intervention may prevent serious health problems caused by an undiagnosed B12 deficiency.

Metformin and Vitamin B12 Deficiency 

While the association between metformin and vitamin B12 is generally acknowledged, it has only been recently that researchers verified the connection. A systematic review published in PLOS One in June 2014 noted heterogeneity among earlier studies, but said there was enough evidence to conclude that vitamin B12 was significantly reduced by metformin in a dose-dependent manner.1

In April 2016, the Journal of Clinical Endocrinology and Metabolism published a large study that evaluated long-term metformin use and vitamin B12 deficiency in patients enrolled in the Diabetes Prevention Program.2 The results showed the following at the 5-year follow-up:

  • Vitamin B12 levels were 10 percent lower in the metformin group than the control group.
  • Vitamin B12 deficiency existed in 4.3 percent of the metformin group, compared to 2.4 percent in the control group.
  • Borderline-low levels of B12 were present in 19 percent of those taking metformin, compared to 9.5 percent in the control participants.

Experts believe that metformin inhibits B12 absorption by acting on calcium-dependent membranes responsible for vitamin B12-intrinsic factor absorption in the terminal ileum. However, this theory could evolve as researchers dig deeper into the molecular mechanisms.

When the American Diabetes Association (ADA) published the Standards of Medical Care in Diabetes in their January 2017 issue, they included vitamin B12, but didn’t offer much in the way of specific recommendations due to the lack of scientific evidence. The ADA standards state:3

  • Metformin is associated with vitamin B12 deficiency.
  • Periodic testing of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy.
  • Supplementation with vitamins likely does not improve outcomes in people with diabetes who do not have an underlying deficiency—evidence in favor of supplementation is rated “C” or low.

Vitamin B12 Concerns in Older Adults

Diabetes professionals continue to debate the clinical significance of low B12 in metformin patients and they still don’t agree about whether screening is justified.4 As a result, patient care varies from one physician to the next.

The thing pharmacists need to remember is that these debates revolve around management of diabetes. The perspective shifts when you consider the age of the patient. Older adults naturally face a higher risk of B12 deficiency for the following reasons:

  • About 10 to 30 percent of adults over the age of 60 have atrophic gastritis, which decreases secretion of stomach acid and lowers absorption of vitamin B12.
  • Less hydrochloric acid can also encourage overgrowth of normal intestinal bacteria that use vitamin B12, further reducing the amount of the nutrient that’s absorbed.
  • Adults with pernicious anemia can’t properly absorb B12—an estimated 2 percent of older adults have this type of anemia.

Atrophic gastritis and pernicious anemia only block absorption of B12 from food; most adults can readily absorb the synthetic form of the vitamin used in supplements and added to fortified foods. Given the large percentage of adults at risk for a deficiency, the Institute of Medicine recommends that everyone over the age of 50 should get most of their daily intake from synthetic B12.5 When you combine the risks of malabsorption from normal aging and metformin, you end up with a cross-section of patients whose health may depend on a professional who counsels them about vitamin B12 deficiency.

Pharmacist Counseling for Elderly Patients Taking Metformin

No one can afford a vitamin B12 deficiency. It’s essential for producing DNA, red blood cells, and maintaining normal neurological function. As a cofactor, B12 is required for the metabolism of homocysteine, fat and protein, and for the formation of the universal methyl donor, S-adenosylmethionine. A deficiency causes anemia and neurological complications, but those who are less anemic have more prominent neurological symptoms and vice versa. Patients with low vitamin B12 may also have a sore tongue, loss of appetite, and constipation.

When you have the opportunity to counsel these patients, remember that vitamin B12 deficiency manifests in ways that are easily confused with other health concerns caused by aging and diabetes. Keep these tips in mind:

  • Symptoms of a deficiency take time to develop. Vitamin B12 is the only water-soluble vitamin that’s stored in the body—the liver can hold about a 3-year supply. Low dietary intake or malabsorption due to metformin will slowly erode the supply until it’s depleted enough to cause symptoms.
  • Vitamin B12 supplements are safe. No toxic or adverse effects have been associated with large intakes of supplemental B12 in healthy people.
  • Oral supplements can treat a deficiency. For many years, it was assumed that injections were needed, but a severe B12 deficiency can be treated with high-dose supplements, while a mild case may only need a multivitamin. A study published in August 2016 reported that oral vitamin B12 at a dose of 1000 mcg daily was adequate to treat patients with pernicious anemia.6
  • Low B12 can cause dizziness, which increases the risk of falls. Polypharmacy in the elderly further raises the risk, so pharmacists should screen patients and collaborate with other health care providers to help them avoid falls.7 You’ll find fall prevention resources for health care providers, including a 3-question risk assessment, at the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) website.8
  • Vitamin B12 deficiency and diabetes both cause peripheral neuropathy. This means that neuropathy in patients taking metformin will be attributed to diabetes without screening for vitamin B12 deficiency. Advise older diabetic patients to talk with their doctors about B12.

Education About B12 and Metformin Prevents a Deficiency

Diabetes professionals may or may not talk to patients about their risk for a B12 deficiency, which means it’s all the more essential for pharmacists to make it a regular part of patient counseling. In addition to aging-related concerns and metformin, other medications can also lower vitamin B12, including proton pump inhibitors, histamine 2 receptor antagonists, and colchicine.9 This issue falls squarely in your area of expertise, so reach out to educate elderly, diabetic adults about their risk for vitamin B12 deficiency.

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Show 9 footnotes

  1. “Vitamin B12 Status in Metformin Treated Patients: Systematic Review,” June 2014,
  2. “Long-Term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study,” April 2016,
  3. “Standards in Medical Care in Diabetes – 2017,” January 2017,
  4. “Metformin Link to Vitamin B12 Deficiency, Neuropathy in Diabetes,” September 2015,
  5. “Vitamin B12,” February 2016,
  6. “Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia,” August 2016,
  7. “The Role of Pharmacists in Preventing Falls Among America’s Older Adults,” November 2016,
  8. “STEADI: Stopping Elderly Accidents, Deaths and Injuries,” September 2016,
  9. “Medications Known to Decrease Vitamin B12 Levels,” October 2015,

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