The Link Between Metformin and B12 Deficiency in 2023

by Michael Gonzales |  September 12, 2023

The Link Between Metformin and B12 Deficiency in 2023

Imagine managing your diabetes with metformin, only to discover that this very treatment may lead to another health issue - vitamin B12 deficiency. This seemingly contradictory scenario is more common than one might think. In 2023, the link between metformin and B12 deficiency, specifically “metformin and B12” deficiency, is well-established, and it is essential for individuals taking metformin to be aware of this connection and take appropriate measures to prevent and manage B12 deficiency. Join us as we delve into this critical relationship, its consequences, and the steps you can take to protect your health.

Short Summary

  • Prolonged metformin usage has been linked to an increased risk of vitamin B12 deficiency and its associated complications.

  • Proton pump inhibitors (PPIs) can increase the risk of vitamin B12 deficiency when used alongside metformin, requiring careful consideration before taking them.

  • Regular monitoring and diagnosis is essential for early detection, while dietary considerations such as increasing intake of B12 rich foods or supplementation may be beneficial in managing this condition.

The Connection Between Metformin and Vitamin B12 Deficiency

The Connection Between Metformin and Vitamin B12 Deficiency
Metformin is a widely prescribed medication that helps manage blood sugar levels in individuals with type 2 diabetes. While it has proven effective in combating insulin resistance, a significant side effect has emerged: an increased risk of metformin vitamin deficiency. Research indicates that prolonged metformin usage results in vitamin B12 deficiency in 22,2% of patients taking metformin. This raises questions about the reason for this correlation and the possible mitigation measures for those taking daily metformin dose.

The connection between metformin use and vitamin B12 deficiency is believed to have several causes, including food cobalamin malabsorption. Other causes are:

1. Alteration of bile acid metabolism
2. Small intestinal bacterial overgrowth
3. Effects on intestinal motility

Interference by metformin on vitamin B12-intrinsic factor absorption in the terminal ileum
Despite these potential causes, treatment and investigation of vitamin B12 deficiency should proceed alongside long-term metformin therapy.

Ignoring this deficiency could lead to harmful health consequences, which will be discussed in the subsequent sections.

How Metformin Affects Vitamin B12 Absorption

Several mechanisms are believed to contribute to metformin’s interference with vitamin B12 absorption. These include:

1. Changes in intestinal motility
2. Bacterial overgrowth
3. Interactions with the intrinsic-factor/vitamin B12 and cubilin complex
4. Impairment of the uptake of B12-intrinsic factor complex by ileal cell surface, a calcium-dependent process

Metformin affects the uptake of B12-intrinsic factor complex by ileal cell surface, a calcium-dependent process, because of impaired calcium availability. This impact on intestinal absorption may contribute to the observed effects.

These factors combine to result in a decrease in the levels of vitamin B12 in the blood, putting metformin users at risk for cobalamin deficiency. Monitoring vitamin B12 levels and considering supplementation if necessary is crucial for metformin users, given that some instances may also result in folate deficiency.

The Role of Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are commonly prescribed medications that help reduce stomach acid production. However, when used alongside metformin, PPIs can further exacerbate the existing risk factors of vitamin B12 deficiency, especially at higher metformin doses. This is due to their potential to cause adverse effects such as:

1. Nausea
2. Vomiting
3. Diarrhea
4. Abdominal pain

Metformin users contemplating the use of PPIs should consult their healthcare provider for advice on potential risks and benefits. A multivitamin supplement might prove beneficial in preventing nutrient deficiencies that could arise from using metformin and PPIs simultaneously.

Identifying and Managing Metformin and B12

Identifying and Managing B12 Deficiency in Metformin Users
Recognizing the signs of vitamin B12 deficiency in metformin users is vital for proper management and prevention of further health complications.

This section will delve into the symptoms and risk factors of B12 deficiency higher metformin dose and the available monitoring and treatment options for metformin users.

Symptoms and Risk Factors

The signs of vitamin B12 deficiency in metformin users can manifest as damage to peripheral nerves, exhaustion, and cognitive dysfunction. Additionally, higher daily metformin doses and prolonged duration of use have been associated with an increased risk of B12 deficiency.

Awareness of these symptoms and risk factors is key for metformin users, as early detection and metformin treatment can stave off additional complications. In some cases, B12 deficiency can be effectively treated with an 8-week course of replacement therapy, long term metformin treatment although longer treatment duration might be necessary for certain individuals. Determining the metformin dose should be based on the average dose taken over the last 6 months. This helps ensure consistent treatment and effectiveness of the medication.

Monitoring and Diagnosis

Monitoring B12 levels in metformin users is of utmost importance, as the drug has the potential to impede the absorption of vitamin B12, thereby increasing the risk of deficiency. Blood and urine samples are obtained in a fasting state to appraise serum vitamin B12 levels. If there is no clinical response to treatment, B12 levels should be reassessed 1-2 months post-treatment.

The new MHRA guidance proposes considering the evaluation of vitamin B12 levels in users of metformin with risk factors for B12 deficiency as part of yearly review blood tests. Regular monitoring of B12 levels is essential in detecting and managing deficiency early, helping prevent further complications.

Treatment Options

Treatment options for vitamin B12 deficiency in metformin users may include oral or intramuscular B12 supplementation. After initiating oral B12 replacement therapy, it is advised to recheck B12 levels after 8-12 weeks. However, there is no requirement to reevaluate B12 levels after initiating intramuscular replacement therapy or upon confirmation of satisfactory absorption in replacement therapy.

Ensuring that B12 levels are within the normal range can help prevent peripheral neuropathy and other complications associated with deficiency. It is critical for metformin users to work closely with their healthcare providers to develop a personalized treatment plan that best suits their needs.

Implications for Patients with Diabetes

Implications for Patients with Diabetes
The consequences of vitamin B12 deficiency for individuals with diabetes are severe and far-reaching. This section will address the heightened risks of diabetic neuropathy, cognitive impairment, and cardiovascular disease resulting from B12 deficiency and the significance of monitoring and managing B12 levels in diabetes patients.

Diabetic neuropathy is a common complication of diabetes and is caused by damage to the nerves.

Diabetic Neuropathy

Diabetic neuropathy is a common symptom of B12 deficiency and can be exacerbated by metformin use. B12 deficiency in metformin users may cause or exacerbate distal symmetrical and autonomic neuropathy in patients with diabetes.

The Michigan Neuropathy Screening Instrument is employed to detect diabetic neuropathy. Monitoring and managing B12 levels enables metformin users to avoid additional nerve damage and complications tied to diabetic neuropathy.

Cognitive Impairment and Cardiovascular Disease

Recent studies have demonstrated that B12 deficiency is correlated with a heightened risk of cognitive impairment and cardiovascular disease. Patients with diabetes are at an increased risk for B12 deficiency, and monitoring and managing B12 levels can assist in decreasing the risk of cognitive impairment and cardiovascular disease.

Cardiovascular disease was characterized by a medical history of coronary heart disease, stroke, or peripheral arterial disease. A specialist would verify diagnosis. Patients with diabetes can safeguard themselves from these severe complications by taking proactive steps to monitor and manage B12 levels.

Prevention Strategies

Prevention Strategies
Preventing vitamin B12 deficiency in metformin users involves more than just monitoring levels and seeking treatment when necessary.

This section will touch upon dietary considerations and calcium supplementation as preventive strategies against B12 deficiency for metformin users.

Dietary Considerations

To prevent vitamin B12 deficiency in metformin users, it is recommended to increase intake of foods rich in vitamin B12, such as meat, fish, eggs, and dairy products. Additionally, consideration should be given to taking vitamin B12 supplements or injections under the guidance of a healthcare professional.

Furthermore, it is advised to regularly monitor B12 levels through blood tests to detect any deficiency early. Maintaining a balanced diet rich in B12 and considering multivitamin supplementation can help metformin users prevent deficiency and the associated health complications.

It is also recommended to have ongoing conversations with a healthcare professional regarding the need for B12 supplementation while on metformin.

Calcium Supplementation

Calcium supplementation does not play a direct role in preventing B12 deficiency in metformin users. It has been observed that metformin can interfere with the absorption of B12 in the body, and calcium supplementation is not known to counteract this effect. Therefore, it is recommended that metformin users monitor their B12 levels regularly and consider B12 supplementation if necessary.

However, calcium supplementation can still be beneficial for overall health. It can assist in:

1. Sustaining robust bones and teeth
2. Decreasing the likelihood of osteoporosis
3. Regulating blood pressure
4. Lessening the risk of certain types of cancer
5. Decreasing the risk of cardiovascular disease


In conclusion, the link between metformin and B12 deficiency is a critical issue for individuals with diabetes. Understanding the connection, recognizing the symptoms, and taking appropriate measures to prevent and manage deficiency are essential in maintaining overall health. By considering dietary modifications, calcium supplementation, and regular monitoring of B12 levels, metformin users can effectively minimize the risk of deficiency and its associated complications.

Take control of your health and be proactive in managing your B12 levels while using metformin. Consult your healthcare provider, monitor your levels, and make informed decisions about your treatment and prevention strategies. Your health is worth the effort, and a proactive approach can help ensure better outcomes for you and your loved ones.

Frequently Asked Questions

Should I take B12 if I take metformin?

If your healthcare provider recommends it, you should take a B12 supplement while taking metformin. This is because low levels of vitamin B12 can cause serious neurological damage and bone marrow production issues, and should be monitored in anyone taking metformin.

A vitamin B12 supplement can help treat the deficiency and prevent further nerve damage.

How quickly can metformin cause B12 deficiency?

Metformin can cause B12 deficiency in a dose-related manner, potentially leading to a prevalence of 20.3% after 9.5 years of use and a 22% prevalence when levels fall below 300 pg/mL.

Dr. Buvat also recommends calcium supplementation for patients on long-term metformin.

Does metformin have side effects from B12?

Metformin can commonly reduce Vitamin B12 levels in patients, resulting in Vitamin B12 deficiency and symptoms such as diarrhea, exhaustion, loss of appetite, pale skin, and bleeding gums.

Taking metformin for a long time can also lead to Vitamin B12 deficiency, so your doctor may check the Vitamin B12 level in your blood and provide vitamin B12 supplements if needed.

What vitamins are not good with metformin?

Vitamin B12 and, sometimes, folic acid can be depleted when taking metformin, so supplementation should be considered.

Monitoring levels of both vitamins is also advised for people on metformin.


Michael Gonzales

Michael has a diverse set of skills and passions, with a full-time career as an airline pilot and a dedicated focus on health and fitness consulting. He understands the importance of balancing a busy lifestyle with maintaining a healthy mind and body, and is committed to helping others achieve the same success. Michael's expertise in health and fitness is not just limited to physical training, but also extends to nutrition, stress management, and overall wellbeing. He takes a holistic approach to health and fitness, helping clients to achieve their goals in a sustainable and fulfilling way. With a strong desire to inspire and motivate others, Michael is always ready to share his time and knowledge with those who seek his guidance. Whether in the air or on the ground, Michael is dedicated to helping others live their best lives.

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