Type 1 Diabetes (T1D) is an autoimmune condition where the body’s immune system attacks and destroys the insulin-producing beta cells in the pancreas, leading to an absolute deficiency of insulin. People with T1D require lifelong treatment with exogenous insulin to manage blood sugar levels. Metformin is a common oral medication primarily used to treat Type 2 Diabetes (T2D), which is characterized by insulin resistance. A person with T1D can take Metformin, but it is not a primary treatment and never replaces insulin therapy. It is typically prescribed as an adjunct therapy for specific T1D patients who also exhibit features of insulin resistance.
Metformin’s Mechanism of Action
Metformin belongs to the biguanide class of medications. Its main effect is lowering glucose in the bloodstream without directly stimulating the pancreas to release insulin. It works through multiple pathways, primarily targeting the liver and muscle tissues. The most significant action involves decreasing the production of glucose by the liver (hepatic gluconeogenesis). Metformin limits this excessive glucose output by activating an enzyme called AMP-activated protein kinase (AMPK), helping to lower fasting blood sugar levels.
This action is distinct from insulin, which works by facilitating the uptake of glucose from the blood into cells. The second primary action is increasing the sensitivity of the body’s tissues, particularly muscle cells, to insulin. It enhances the effectiveness of administered insulin, allowing glucose to move more efficiently from the bloodstream into the cells for energy. Unlike some other diabetes medications, Metformin does not generally cause hypoglycemia when used alone because it does not increase insulin secretion.
Clinical Rationale for Use in Type 1 Diabetes
Metformin is not approved by the U.S. Food and Drug Administration (FDA) for T1D, but it is often used “off-label” as an add-on therapy for patients who have developed insulin resistance. This resistance, sometimes called “double diabetes,” occurs when a person with T1D develops the insulin resistance features typical of T2D. It often arises in T1D patients who are overweight or obese and require high doses of insulin to maintain glycemic control. The primary goal of prescribing Metformin is to act as an insulin sensitizer, making injected insulin work more effectively.
By improving insulin sensitivity, Metformin can potentially lead to a reduction in the total daily dose of insulin required. This reduction is beneficial, as high-dose insulin therapy is often associated with weight gain. Metformin has also been shown to help with modest weight loss and a reduction in body mass index (BMI) for overweight T1D patients. The medication may also offer cardiovascular benefits, such as reducing low-density lipoprotein (LDL) cholesterol and potentially slowing the progression of atherosclerosis.
Clinical guidelines in some regions recommend considering Metformin as an adjunctive treatment for overweight T1D patients seeking to optimize blood sugar control while minimizing insulin requirements. However, studies on the long-term impact of Metformin on reducing the A1C level in T1D patients have yielded variable results.
Monitoring and Management of Potential Side Effects
The addition of Metformin to an insulin regimen for a T1D patient requires careful monitoring to mitigate potential adverse events.
Gastrointestinal Issues
The most frequent side effects are gastrointestinal, including nausea, diarrhea, abdominal discomfort, and gas. These symptoms can affect up to 25% of users. They may be lessened by starting with a low dose, taking the medication with food, or switching to an extended-release formulation.
Hypoglycemia Risk
While Metformin itself has a low risk of causing hypoglycemia, its introduction alongside insulin necessitates a careful reduction in the insulin dose. If the insulin dose is not adequately adjusted, the enhanced insulin sensitivity provided by Metformin can increase the risk of low blood sugar. This risk must be carefully managed through continuous glucose monitoring and patient education. The risk of severe hypoglycemia may be greater if the patient is not frequently monitoring their blood sugar levels.
Lactic Acidosis
A rare but serious complication associated with Metformin is lactic acidosis, where lactic acid builds up in the bloodstream. Symptoms include extreme weakness, tiredness, rapid breathing, and unusual muscle pain. This condition is more likely to occur in individuals with pre-existing kidney or liver impairment, or those who consume excessive alcohol. Screening for these risk factors is performed before prescribing the drug.
Vitamin B12 Deficiency
Long-term use of Metformin is associated with a potential decrease in Vitamin B12 levels. Low B12 can lead to symptoms like tiredness, weakness, and potentially peripheral neuropathy. Regular monitoring of Vitamin B12 levels is recommended for patients on extended Metformin therapy.