Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D) both result in high blood sugar but have distinct causes. T1D is an autoimmune disease leading to an absolute deficiency of insulin, requiring external replacement. T2D is characterized by insulin resistance, where cells fail to respond effectively to insulin. Metformin is a first-line treatment for T2D, primarily improving the body’s response to insulin. Due to the difference in underlying causes, Metformin was not initially considered for T1D management.
Adjunctive Therapy in Type 1 Diabetes
Metformin is not approved by the Food and Drug Administration (FDA) for treating T1D, but healthcare professionals frequently use it off-label as an adjunctive therapy. It is added to a patient’s established insulin regimen, never replacing insulin. This practice is typically reserved for adults with T1D who exhibit insulin resistance, often called “double diabetes.”
Insulin resistance is often indicated by a body mass index (BMI) in the overweight or obese range, requiring a high total daily dose of insulin. Clinical guidance recommends considering Metformin for adults with T1D who have a BMI of 25 kg/m$^2$ or higher to optimize glucose control. This off-label use is common; population data shows approximately 15% of adults with T1D have received a prescription for Metformin.
Physiological Benefits Beyond Blood Sugar Control
Metformin improves the body’s sensitivity to administered insulin, providing physiological advantages to T1D patients with insulin resistance. Its primary mechanism is reducing the liver’s production of glucose, known as hepatic gluconeogenesis. It also enhances glucose uptake and utilization in peripheral tissues, such as skeletal muscle. Metformin achieves this by activating AMP-activated protein kinase (AMPK), which improves the efficiency of insulin signaling pathways. By increasing peripheral insulin sensitivity, Metformin decreases the total amount of exogenous insulin needed, with studies showing a reduction in daily requirements by around 12%.
The drug offers several benefits extending to overall metabolic health. The reduction in daily insulin dose can lead to modest weight loss, counteracting the weight gain often associated with high-dose insulin therapy. Metformin also favorably affects lipid profiles, decreasing low-density lipoprotein (LDL) cholesterol and triglycerides. These positive effects on weight and lipids translate into potential long-term cardiovascular benefits, including reduced progression of atherosclerosis.
Essential Safety and Monitoring Requirements
The use of Metformin as an adjunct therapy in T1D requires close clinical supervision. The most common adverse effects are gastrointestinal, including diarrhea, nausea, and abdominal pain, which are often mitigated by starting at a low dose and titrating slowly. A more serious, though rare, safety concern is the risk of lactic acidosis, a potentially life-threatening buildup of lactic acid. This risk is significantly elevated with impaired kidney function, making baseline and routine monitoring of kidney function mandatory before and during therapy. Metformin does not appear to increase the risk of severe hypoglycemia or diabetic ketoacidosis (DKA) when used appropriately.
Metformin can interfere with the absorption of Vitamin B12, potentially leading to a deficiency over time. Physicians often monitor B12 levels, especially in patients on long-term therapy, to prevent complications like anemia or neuropathy.