Can glucagon be administered orally?

Glucagon Cannot Be Administered Orally

Glucagon cannot be administered orally as it is destroyed in the gastrointestinal tract before absorption can occur, making oral administration ineffective for treating hypoglycemia. 1

Why Oral Glucagon Is Not Viable

Glucagon is a peptide hormone that is rapidly degraded by digestive enzymes in the gastrointestinal tract. According to the FDA drug information, "Glucagon is not active when taken orally because it is destroyed in the gastrointestinal tract before it can be absorbed." 1

The American Diabetes Association's 2024 and 2025 Standards of Care in Diabetes clearly outline the approved routes of administration for glucagon, which include:

1. Injection (subcutaneous or intramuscular)

   • Traditional powder requiring reconstitution
   • Ready-to-inject prefilled pens and syringes 2

2. Intranasal administration

   • Nasal powder formulation 2

Appropriate Glucagon Administration Routes

The current guidelines emphasize that glucagon is indicated specifically "for the treatment of hypoglycemia in people unable or unwilling to consume carbohydrates by mouth." 2 The approved administration routes include:

• Injectable formulations:

  • Traditional powder with diluent for reconstitution (1 mg)
  • Prefilled pens/syringes (0.5 mg, 1 mg)
  • Dasiglucagon prefilled pens/syringes (0.6 mg) 2

• Nasal formulation:

  • Nasal powder (3 mg) 2

Clinical Implications

For patients at risk of severe hypoglycemia, the following approach is recommended:

1. First-line treatment for conscious patients who can swallow: Oral glucose or simple carbohydrates 2

   • Glucose tablets are preferred over dietary sugars 2
   • 15-20g of carbohydrate should be administered 2

2. For patients unable to take oral carbohydrates:

   • Glucagon should be administered via injection or intranasal route 2
   • Family members, caregivers, and others in close contact should be trained in glucagon administration 3

Important Considerations

• The newer formulations (intranasal and ready-to-inject) are preferred due to their ease of administration, resulting in more rapid correction of hypoglycemia 2, 3

• All individuals treated with insulin or at high risk of hypoglycemia should be prescribed glucagon, yet appropriate glucagon prescribing remains very low in current practice 2

• Glucagon products should be replaced when they reach their expiration date and stored according to specific product instructions 2

• After glucagon administration, patients should be monitored and given oral carbohydrates once alert to prevent recurrent hypoglycemia 3

Common Pitfalls to Avoid

1. Attempting oral administration: This is ineffective as glucagon is destroyed in the GI tract 1

2. Administering insulin during hypoglycemia: Caregivers should be explicitly educated to never administer insulin to individuals experiencing hypoglycemia 2

3. Inadequate training: Those in close contact with high-risk patients should be properly trained in glucagon administration techniques 3

4. Expired products: Glucagon products should be checked regularly and replaced when expired 2

While researchers have investigated oral delivery systems for peptide hormones like GLP-1 analogs 4, no such viable delivery system exists for glucagon in clinical practice. Current evidence and guidelines clearly indicate that glucagon must be administered via injection or intranasal routes for effective treatment of hypoglycemia.