Diabetes is the most common metabolic disorder in the world. In 2019, approximately 9.3 percent of adults between the ages of 20 and 79 years worldwide were known to have diabetes. While diabetes is a collective term, there are several different types: Type 1, Type 2 and Gestational.

Diabetes is often treated by metformin, which is an antihyperglycemic drug. Primarily relied on to treat Type 2 diabetes, metformin is preferred over other drugs because it more effectively reduces hemoglobin bound to glucose (HbA1C).

Metformin helps diabetic patients through the following mechanisms:

  • Reduces the production of glucose in the liver
  • Interferes with and reduces vitamin B12 absorption in the small intestine
  • Decreases insulin resistance of cells, which increases their glucose intake and utilization

It takes up to eight hours for a dosage of metformin to reach maximum plasma concentration levels. There are no reported immediate severe adverse reactions.

Common side effects include:

  • Nausea
  • Gastric irritation
  • Abdominal pain
  • Diarrhea
  • Weakness in limbs
  • Muscular pain
  • Vitamin B12 deficiency

Diabetes and Vitamin B12 Deficiency

Vitamin B12 is also called cobalamin. It is a water-soluble vitamin that plays a prominent role in many of the body’s metabolic and physiological processes, including:

  • Maturation of red blood cells (RBS) in the bone marrow
  • Myelinogenesis, a process wherein the myelin sheath surrounding the body’s axon cells proliferates and maturates
  • Gene expression required for the metabolism of fatty and amino acids

The primary sources of this vitamin are:

  • Meat
  • Dairy products such as cheese, yogurt, and low-fat milk
  • Eggs
  • Liver
  • Fish
  • Fortified cereal

According to the National Academy of Medicine, the daily requirement (recommended dietary allowance – RDA) of vitamin B-12 is:

  • 2.4 micrograms/day (µg/day) for both men and women 14 years and up
  • 0.4 to 0.5 µg/day for neonates or infants from birth to 12 months of age
  • 0.9 to 18 µg/day for children between 1 and 13 years of age
  • 2.6 µg/day for pregnant women
  • 2.8 µg/day for lactating women

People who are 50 years and older are recommended to take additional supplements in addition to their typical daily allowance.

A concentration of less than 200 picograms per deciliter (pg/dl) in serum constitutes vitamin b12 deficiency. Individuals with Type 2 diabetes are more likely to be deficient.

A case study was conducted on a group of 81 patients with Type 2 diabetes who were on metformin for more than five years. It was discovered that 8 percent of these patients were vitamin B-12 deficient, and 26 percent were borderline.

The study concluded that a higher and prolonged concentration of metformin in the body is a cause of vitamin B12 deficiency in patients with Type 2 diabetes. While the depletion begins as early as four months after beginning metformin treatment, the symptoms appear after nearly five years. This is because the liver stores vast amounts of vitamin B12; once the reserve amount is depleted, symptoms manifest.

Role of Metformin in Vitamin B-12 Deficiency

The primary cause of vitamin B12 deficiency in patients using metformin is interference with absorption. It disrupts calcium dependant vitamin absorption, which results in lower serum vitamin B-12 levels. This effect can be reversed by proper intake of calcium.

The following metformin effects also influence vitamin B12 deficiency:

  • Decreased gut motility
  • Bacterial overgrowth in the digestive tract
  • Competitive inhibition
  • Cubulin endocytic receptor interaction
  • Intrinsic factor (IF) interaction


If there are no underlying conditions that cause vitamin B12 deficiency, such as anemia, treatment is straightforward. In severe deficiency, your physician may recommend no longer taking metformin.

The B12 dosage for diabetics has several protocols. Different physicians may follow different protocols, and the dosage may vary accordingly. A high dose of 1000 to 2000mg per day (mg/day) is given to patients with severe symptoms, orally or via injection.

In some instances, the initial dosage is administered via intramuscular or intravenous injection, which is then followed by oral dosages once the B12 levels stabilize. Both chewable and sublingual tablets are available. A nasal spray may also be available. Your physician will prescribe the appropriate dosage and administration method.

While neurological damage caused by vitamin B12 deficiency cannot be reversed, additional progression and damage can be prevented with proper treatment.


Disclaimer: Please note that the contents of this community article are strictly for informational purposes and should not be considered as medical advice. This article, and other community articles, are not written or reviewed for medical validity by Canadian Insulin or its staff. All views and opinions expressed by the contributing authors are not endorsed by Canadian Insulin. Always consult a medical professional for medical advice, diagnosis, and treatment.