Metformin remains the most common oral drug for the management of type 2 diabetes because of its effectiveness in controlling blood glucose levels. However, emerging studies indicate a greater risk of vitamin B12 deficiency, particularly with long-term metformin use.
This deficiency is associated with a number of serious health problems, including neurological problems such as peripheral neuropathy and blood issues such as anemia, both of which negatively impact quality of life.
The prevalence of type 2 diabetes is increasing worldwide, posing significant public health challenges. Factors contributing to this increase include increased obesity, sedentary lifestyles and an aging population.1 Metformin is a common first-line treatment for the management of type 2 diabetes.
However, long-term use of metformin is associated with decreased absorption of vitamin B12.2 This vitamin is important for nerve function and the production of red blood cells. Deficiency leads to serious health problems, including peripheral neuropathy and megaloblastic anemia, which greatly affects the quality of life of diabetics.
These findings highlight the importance of regular monitoring of vitamin B12 levels in individuals receiving metformin therapy to prevent potential adverse effects.
Early detection of B12 deficiency in metformin users
In the year In the early 1970s, health care professionals began to notice an alarming trend among diabetic patients treated with metformin. A study published in the British Medical Journal found that individuals on long-term metformin therapy showed symptoms such as peripheral neuropathy and macrocytic anemia – symptoms of vitamin B12 deficiency.3
Further investigations indicate that metformin interferes with calcium absorption by disrupting the binding of the vitamin B12-intrinsic factor complex to ileal receptors. This study has prompted recommendations for regular monitoring of vitamin B12 levels in patients prescribed metformin.
High prevalence of vitamin B12 deficiency in long-term metformin users
Studies have consistently shown that people with type 2 diabetes who are on long-term metformin therapy have significantly higher rates of vitamin B12 deficiency compared to those who are not using the drug.4 Up to 93% of diabetics treated with metformin may develop this deficiency over time, highlighting the need for greater awareness and proactive management.
Higher doses of metformin and longer duration of treatment were directly associated with increased deficiency.5 Patients taking more than 2,000 milligrams (mg) daily or taking more than four years are particularly at risk. This suggests that clinicians should consider dosage and length of treatment when prescribing metformin and implement regular monitoring protocols.
Age, high doses, and long-term use of metformin increase the risk of vitamin B12 deficiency. Older patients and those requiring higher doses may benefit from more frequent screening and supplementation to prevent complications.6
Vitamin B12 deficiency worsens nerve pain and impairs cognitive health, leading to issues such as memory loss and dementia. This interaction between diabetes management and nutritional deficiencies highlights the importance of ensuring overall health, not just blood glucose control.
How does metformin interfere with vitamin B12 absorption?
Metformin disrupts the absorption of vitamin B12 by interfering with calcium ions in the intestine, which prevents the formation of the vitamin B12-intrinsic factor complex, which is necessary for absorption in the eye.7 In addition, metformin affects the receptors responsible for identifying and absorbing this complex, further reducing the absorption of vitamin B12.
In addition, metformin’s effect on intestinal motility contributes to interference with vitamin B12 absorption. The drug changes the gastrointestinal tract, which affects the bioavailability of important substances, including vitamin B12.
This effect is especially pronounced in patients who take high doses for a long time, which requires a thorough examination of the dosage and the need for supplementation. Recognizing this multifactorial disruption is key to understanding why metformin patients are at risk for vitamin B12 deficiency.
Effects of vitamin B12 deficiency
The neurological implications of vitamin B12 deficiency in patients taking metformin are of particular concern. Peripheral neuropathy, characterized by tingling, numbness or burning in the hands and feet, is a common condition that can lead to serious nerve damage if left untreated. This complex condition often mimics diabetic neuropathy, making it difficult for health care providers to differentiate between the two conditions without proper diagnosis.
In addition to peripheral neuropathy, vitamin B12 deficiency increases the risk of cognitive impairment, such as memory impairment, concentration problems, and dementia. These cognitive symptoms affect quality of life, especially in older adults who are at risk for cognitive decline. Management of diabetes and the complex effect of vitamin deficiency is a great challenge to maintain physical and mental health.
In hematology, vitamin B12 deficiency causes megaloblastic anemia, a condition in which red blood cells are too large and ineffective in oxygen transport. Symptoms of this type of anemia are fatigue, weakness, dizziness and shortness of breath.
These symptoms exacerbate the taxing demands of managing type 2 diabetes, leading to higher health care visits, additional medical costs, and decreased patient safety. Therefore, early detection and treatment of vitamin B12 deficiency are critical to maintaining overall health and controlling diabetes.
Metformin-wide societal impact of vitamin B12 deficiency
Long-term use of metformin to control type 2 diabetes has significant public health implications. Metformin in combination with vitamin B12 deficiency causes an increase in neuropathy and anemia in diabetic patients. These health problems will require more medical interventions, which will put more pressure on health care systems due to the already increasing incidence of diabetes.
Economically, the implications are profound. Management of problems caused by vitamin B12 deficiency often requires medical consultation, additional laboratory tests, and additional treatments such as vitamin B12 supplementation. This not only increases the cost of health care for individuals, but also increases the overall financial burden on the health care infrastructure, diverting resources from other critical areas of patient care.
Strategies to reduce vitamin B12 deficiency in metformin users
Serum vitamin B12 levels and additional biomarkers such as homocysteine and methylmalonic acid provide more sensitive indicators for early detection of deficiency.8 Elevated homocysteine and methymalonic acid levels are particularly useful in diagnosing functional vitamin B12 deficiency, even when serum B12 levels are borderline.
Using these biomarkers, health care providers can identify a deficiency before symptoms are clinically apparent, ensuring timely intervention. In addition, also consider:
• Supplement – Oral or intramuscular vitamin B12 supplements may help restore adequate levels, depending on the severity of the deficiency.9 Oral supplementation in doses ranging from 1,000 to 2,000 micrograms daily is generally effective for mild to moderate deficiency.
Intramuscular injections, particularly monthly, may be more appropriate for patients with severe deficiency or wear and tear. Patients on long-term metformin therapy should discuss additional options with their healthcare providers to determine the best approach based on individual needs and risk factors.
• Dietary changes – It is important to include foods rich in B12 such as meat and dairy products. In particular, vegetarians and vegans who are prone to vitamin B12 deficiency due to dietary restrictions should consider supplements.10 Regular nutritional assessments help identify gaps in nutrition and guide appropriate dietary adjustments to support proper vitamin B12 levels.
• Regular monitoring – Regular blood tests every six to 12 months allow for early intervention to maintain B12 levels. Monitoring is important for patients who have been taking high doses of metformin or have been taking the drug for many years. Establishing a regular screening schedule can help catch defects early.
• Patient Education – Patients should be educated about the risks associated with metformin and the importance of a healthy lifestyle for diabetes prevention and treatment. Many patients are unaware of the connection between metformin use and vitamin B12 deficiency and the potential for safe diabetes treatment.
Lifestyle strategies work better than metformin for diabetes management
Lifestyle changes such as diet and exercise can prevent type 2 diabetes more effectively than metformin alone, reducing drug dependency and reducing the risk of vitamin B12 deficiency.11
Studies show that weight loss, increased exercise, and dietary changes can significantly improve insulin sensitivity and glycemic control, allowing patients to reduce or stop using metformin. Such lifestyle choices support overall nutritional health, thereby reducing the risk of nutrient deficiencies.
