Metformin is a widely prescribed medication for managing type 2 diabetes. Peripheral neuropathy, a condition characterized by nerve damage, is also a common issue for individuals with diabetes. While diabetes itself is a primary cause of this nerve damage, research has highlighted a connection between the long-term use of metformin and an increased risk of developing neuropathy.
Understanding Diabetic Neuropathy
Diabetic neuropathy is nerve damage that can occur in people with diabetes. The condition is primarily driven by prolonged exposure to high blood sugar (hyperglycemia). Over time, elevated glucose can injure the walls of the small blood vessels, or capillaries, that supply nerves with oxygen and nutrients. This impairment of blood flow starves the nerve fibers, leading to damage and dysfunction.
This nerve damage most commonly manifests as peripheral neuropathy, affecting the longest nerves first. This results in a “stocking-glove” distribution of symptoms, starting in the toes and feet and progressing up the legs, and later affecting the hands and arms. The sensory nerves are often the first to be impacted, causing tingling, numbness, or burning sensations. As the damage progresses, it can affect motor nerves, leading to muscle weakness and loss of coordination.
The process is gradual, with symptoms developing over several years. The severity of diabetic neuropathy often correlates with how long a person has had diabetes and how well their blood sugar has been controlled. Consistent metabolic stress from high blood sugar also contributes to inflammation and further damage to the nerve cells.
The Metformin and Vitamin B12 Connection
A distinct mechanism links metformin use to neuropathy, separate from nerve damage caused by high blood sugar. Research shows that metformin can interfere with vitamin B12 absorption in the digestive system. It is thought to affect a calcium-dependent process in the terminal ileum, the final section of the small intestine, where B12 is absorbed. Long-term use of the medication can lead to a depletion of the body’s B12 stores.
Vitamin B12 is necessary for the health of the nervous system. It is a component in the synthesis and maintenance of the myelin sheath, a fatty substance that insulates nerve fibers. This sheath allows for the rapid transmission of electrical impulses along the nerves. When B12 levels are insufficient, the myelin sheath can degrade in a process called demyelination.
This breakdown of the protective nerve covering disrupts normal nerve signaling, leading to the symptoms of peripheral neuropathy. The resulting nerve damage is not directly caused by diabetes but by a medication-induced nutrient deficiency. Studies indicate that the risk of B12 deficiency, and consequently neuropathy, increases with both the dosage and duration of metformin treatment.
Identifying Symptoms and Risk Factors
The symptoms of peripheral neuropathy, whether from diabetes or metformin-induced B12 deficiency, are largely indistinguishable. Patients often report a sensation of tingling, “pins and needles,” or numbness in their feet and hands. Many experience burning or sharp, stabbing pains, which can be constant or intermittent and often worsen at night. As the condition progresses, a loss of sensation can occur, increasing the risk of injuries to the feet going unnoticed.
Several factors increase the risk of developing neuropathy associated with metformin use. These risk factors include:
- The duration of treatment, as individuals taking metformin for five years or more are at a higher risk.
- Higher daily doses of the medication, as one study found that a daily dose over 2.0 g/d was associated with the highest risk.
- Older age, as the body’s ability to absorb B12 can naturally decrease over time.
- Poor dietary habits, particularly a diet low in animal products which are the primary source of vitamin B12.
Diagnosis and Management Strategies
When a patient on metformin presents with neuropathy symptoms, a healthcare provider will determine the underlying cause. The diagnostic process involves a physical examination of reflexes, sensation, and muscle strength in the extremities. A primary step is to perform blood tests to measure serum vitamin B12 levels. In some cases, levels of methylmalonic acid (MMA) and homocysteine may also be checked, as these can be more sensitive indicators of a B12 deficiency.
The primary management strategy for metformin-associated neuropathy is replenishing vitamin B12. This is accomplished through supplementation with oral tablets, sublingual (under the tongue) forms, or injections. Injections are used for individuals with severe deficiencies or absorption issues. Regular monitoring of B12 levels helps ensure the supplementation is effective.
Patients should not stop taking metformin without consulting their doctor. The benefits of metformin for controlling blood sugar and reducing long-term diabetic complications often outweigh the risk of B12 deficiency. Since both types of neuropathy can coexist, maintaining good glycemic control remains a foundation of treatment. The standard approach is to address the B12 deficiency while continuing metformin.