Can type 1 diabetics safely take GLP-1 (Glucagon-Like Peptide-1) receptor agonists and insulin?

GLP-1 Receptor Agonists in Type 1 Diabetes: Safety and Efficacy

Type 1 diabetics can safely take GLP-1 receptor agonists alongside insulin, with studies showing modest improvements in glycemic control, weight reduction, and decreased insulin requirements, though this remains an off-label use. 1, 2

Evidence for GLP-1 RAs in Type 1 Diabetes

Efficacy

• Clinical trials with liraglutide 1.8 mg daily in type 1 diabetes have demonstrated:
  • Modest A1C reductions (approximately 0.4%)
  • Significant weight loss (about 5 kg)
  • Reduced insulin requirements 1
• A recent meta-analysis of 7 randomized controlled trials found:
  • Greater reductions in HbA1c (mean difference -0.21%)
  • Significant weight loss (mean difference -3.53 kg)
  • Reduced daily bolus insulin requirements 2
• A 2024 real-world study of 144 patients with type 1 diabetes showed consistent benefits over 18 months with GLP-1 RAs:
  • HbA1c reduction of 0.5-0.8%
  • Weight loss of 2.4-3.6 kg
  • Decreased basal insulin requirements 3

Safety Considerations

• GLP-1 RAs are not FDA-approved for type 1 diabetes 1
• Safety profile in type 1 diabetes appears similar to type 2 diabetes:
  • Common side effects include gastrointestinal symptoms (nausea, vomiting) 1
  • In the 2024 study, only 8.3% of patients experienced GI adverse events 3
  • No significant increase in severe hypoglycemia when properly managed 3

Practical Implementation

Patient Selection

1. Consider GLP-1 RAs as adjunctive therapy in type 1 diabetes patients who:
   • Have inadequate glycemic control despite optimized insulin therapy
   • Would benefit from weight reduction
   • Have excessive postprandial glucose excursions

Insulin Adjustment

1. When initiating a GLP-1 RA in a type 1 diabetes patient:
   • Reduce basal insulin dose by approximately 20% initially 4
   • Monitor closely for hypoglycemia, especially during the first few weeks
   • Adjust bolus insulin based on carbohydrate intake and glucose monitoring

Monitoring Recommendations

1. More frequent blood glucose monitoring or continuous glucose monitoring during initiation
2. Regular follow-up visits (every 1-3 months initially)
3. Monitor for:
   • Glycemic control (HbA1c, time in range)
   • Weight changes
   • Gastrointestinal side effects
   • Insulin requirements

Important Caveats and Pitfalls

1. Risk of DKA: Unlike type 2 diabetes, type 1 diabetes patients are insulin-dependent and at higher risk of diabetic ketoacidosis. Insulin should never be discontinued when starting GLP-1 RAs 1

2. Medication Selection: While multiple GLP-1 RAs exist, most studies in type 1 diabetes have been conducted with liraglutide, with newer evidence for semaglutide 3

3. Off-Label Use: Patients should be informed that GLP-1 RAs are not FDA-approved for type 1 diabetes 1

4. Insulin Adjustments: Improper insulin dose reduction when starting GLP-1 RAs could lead to hyperglycemia or DKA; conversely, failure to reduce insulin appropriately could increase hypoglycemia risk

5. Cost and Access: Insurance coverage for off-label use may be limited, creating potential barriers to access

The combination of insulin and GLP-1 RAs represents a promising approach for selected patients with type 1 diabetes, particularly those struggling with weight management or requiring large insulin doses. While not standard of care, the evidence suggests this combination can be safely implemented with appropriate monitoring and insulin adjustments.