Can Glucagon-like peptide-1 receptor agonists (GLP-1RA) be used in Type 1 Diabetes Mellitus (Type 1 DM)?

From the Guidelines

GLP-1 receptor agonists (GLP-1RAs) can be used as adjunctive therapy in type 1 diabetes mellitus, but they are not FDA-approved for this specific indication, and their use should be guided by the most recent evidence and patient-specific factors. According to the most recent study 1, GLP-1RAs have been shown to have modest benefits in type 1 diabetes, including improved glycemic control, reduced glycemic variability, decreased insulin requirements, and potential weight loss. Medications like semaglutide, liraglutide, and dulaglutide may be prescribed off-label alongside insulin therapy in type 1 diabetes patients.

Key Considerations

• Typical starting doses follow standard protocols (e.g., semaglutide starting at 0.25mg weekly, titrating up to 0.5-1mg weekly)
• When adding a GLP-1RA to a type 1 diabetes regimen, insulin doses often need reduction by approximately 10-20% initially to prevent hypoglycemia, with further adjustments based on blood glucose monitoring
• Patients should be monitored for gastrointestinal side effects and the risk of diabetic ketoacidosis, which can occur with reduced insulin doses
• GLP-1RAs do not replace insulin therapy in type 1 diabetes but serve as complementary treatment

Benefits and Risks

• Benefits for type 1 diabetes patients may include improved glycemic control, reduced glycemic variability, decreased insulin requirements, and potential weight loss
• Risks include gastrointestinal side effects and the risk of diabetic ketoacidosis, which can occur with reduced insulin doses
• The most recent study 1 highlights the importance of careful patient selection and monitoring when using GLP-1RAs in type 1 diabetes.

From the FDA Drug Label

• Not indicated for use in type 1 diabetes mellitus or treatment of diabetic ketoacidosis (1) The FDA drug label for semaglutide (OZEMPIC) explicitly states that it is not indicated for use in type 1 diabetes mellitus.

• The label clearly contraindicates the use of semaglutide in type 1 diabetes mellitus.
• Therefore, GLP-1RA should not be used in type 1 diabetes mellitus, according to the FDA drug label for semaglutide 2.

From the Research

GLP-1RA Use in Type 1 Diabetes

• GLP-1 receptor agonists (GLP-1RAs) have been studied as a potential treatment for type 1 diabetes mellitus (T1DM) 3, 4, 5, 6, 7
• The use of GLP-1RAs in T1DM has been shown to improve glycemic control, reduce weight, and decrease insulin requirements 3, 4, 5, 6
• Studies have demonstrated that GLP-1RAs can be used as an add-on therapy to insulin in T1DM patients, particularly those who are overweight or obese and not at glycemic goals despite aggressive insulin therapy 3, 5
• The most commonly used GLP-1RAs in T1DM are liraglutide and semaglutide, with liraglutide having the strongest evidence for use in overweight or obese adult patients with uncontrolled T1DM 3, 4

Efficacy and Safety

• GLP-1RAs have been shown to reduce HbA1c levels, weight, and daily insulin doses in T1DM patients 4, 5, 6
• The use of GLP-1RAs in T1DM has been associated with a low risk of hypoglycemia and gastrointestinal adverse events 3, 4, 5, 6
• However, gastrointestinal adverse events, such as nausea, have been reported in some studies 3, 5
• Diabetic ketoacidosis (DKA) has been reported in some cases of GLP-1RA use in T1DM, particularly with SGLT2 inhibitors 6

Patient Selection

• GLP-1RAs may be beneficial for T1DM patients who are overweight or obese and not at glycemic goals despite aggressive insulin therapy 3, 5
• Patients with detectable C-peptide and/or those who cannot achieve glycemic goals without hypoglycemia may also benefit from GLP-1RA therapy 5
• Further studies are needed to evaluate the potential impact of GLP-1RAs on clinical outcomes such as microvascular and macrovascular complications in T1DM patients 5