Glucagon Administration for Hypoglycemia
For severe hypoglycemia, glucagon should be administered intramuscularly (IM), subcutaneously (SC), or intranasally, with newer intranasal and ready-to-inject formulations preferred over traditional reconstitution kits due to their ease of administration and more rapid correction of hypoglycemia. 1, 2
Routes of Administration
Glucagon can be administered via three primary routes for treating severe hypoglycemia 3:
- Intramuscular (IM) injection: Into the upper arm, thigh, or buttocks 3
- Subcutaneous (SC) injection: Into the upper arm, thigh, or buttocks 3
- Intranasal administration: Using nasal powder formulations 1, 2
- Intravenous (IV) administration: Only under medical supervision in healthcare settings 3
Preferred Formulations
Intranasal and ready-to-inject glucagon preparations are now preferred over traditional reconstitution kits because they are easier to administer by untrained caregivers, resulting in more rapid correction of hypoglycemia 1, 2. Traditional glucagon kits require reconstitution immediately prior to injection, a process prone to error or omission by non-medical personnel 4.
Available formulations include 1:
- Intranasal powder (3 mg)
- Prefilled pens or syringes (0.5 mg, 1 mg)
- Dasiglucagon prefilled pens (0.6 mg)
- Traditional injection powder requiring reconstitution (1 mg)
Dosing for Severe Hypoglycemia
Adults and Children ≥25 kg (or ≥6 years with unknown weight):
- 1 mg (1 mL) administered IM, SC, or intranasally 3
- If no response after 15 minutes, an additional 1 mg dose may be administered while waiting for emergency assistance 3
Children <25 kg (or <6 years with unknown weight):
- 0.5 mg (0.5 mL) administered IM, SC, or intranasally 3
- If no response after 15 minutes, an additional 0.5 mg dose may be administered while waiting for emergency assistance 3
Expected Response and Monitoring
- Glucagon typically increases blood glucose within 5-15 minutes after administration 2, 5
- Blood glucose should be monitored after administration to ensure adequate response 2
- Once the patient responds and can swallow, give oral carbohydrates to restore liver glycogen and prevent recurrence of hypoglycemia 3
Clinical Efficacy Evidence
Research demonstrates that intranasal glucagon is highly effective and non-inferior to IM glucagon 4, 6:
- In a randomized crossover trial of 75 adults with type 1 diabetes, intranasal glucagon (3 mg) achieved success in 98.7% of cases versus 100% for IM glucagon (1 mg), with mean time to success of 16 minutes versus 13 minutes 4
- Meta-analysis of 8 studies involving 269 patients showed equivalent effectiveness between intranasal and IM/SC glucagon (OR 0.80,95% CI 0.28-2.32) 6
Who Should Be Prescribed Glucagon
All individuals treated with insulin—even basal-only regimens—should be prescribed glucagon 1. Glucagon may also be considered for persons taking sulfonylureas who meet criteria for high hypoglycemia risk 1.
Caregiver Training Requirements
Family members, roommates, school personnel, childcare professionals, correctional staff, and coworkers should be trained on glucagon administration 1, 5. Training should include 1:
- Where the glucagon product is kept
- When to administer it
- How to administer it
- Explicit education to never administer insulin to individuals experiencing hypoglycemia 1
Important Clinical Considerations
Common Side Effects:
- Nausea and vomiting are common after glucagon administration 5
- Head/facial discomfort occurs in approximately 25% of intranasal administrations 4
Limitations of Efficacy:
- Glucagon is only effective if sufficient hepatic glycogen is present 3
- Patients in states of starvation, with adrenal insufficiency, or chronic hypoglycemia may not have adequate hepatic glycogen for glucagon to be effective and should be treated with glucose instead 3
Storage and Replacement:
- Replace glucagon products when they reach their expiration date 1, 2
- Store according to specific product instructions to ensure safe and effective use 1, 2
Emergency Protocol
After glucagon administration 3: