Introduction
Glucagon is a polypeptide hormone secreted by the alpha cells of the pancreatic islets of Langerhans. As a medication, it is a critical agent used for the treatment of severe hypoglycemia and as a diagnostic aid in radiologic examinations. This monograph provides a comprehensive overview of glucagon's pharmacology, clinical applications, and safety profile.
Mechanism of Action
Glucagon exerts its effects primarily through activation of specific G-protein-coupled glucagon receptors in the liver. This activation stimulates adenylate cyclase, increasing intracellular cyclic AMP (cAMP) levels. The elevated cAMP activates protein kinase A, which subsequently phosphorylates and activates key enzymes involved in glycogen metabolism. The primary result is the promotion of glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis (formation of glucose from non-carbohydrate sources), leading to a rapid increase in blood glucose levels. Glucagon also has relaxant effects on smooth muscle of the gastrointestinal tract, which is utilized in its diagnostic applications.
Indications
FDA-Approved Indications:- Treatment of severe hypoglycemia in patients with diabetes mellitus
- Diagnostic aid in radiologic examinations to temporarily inhibit gastrointestinal motility
- Management of beta-blocker overdose
- Management of calcium channel blocker overdose
- Treatment of anaphylaxis when epinephrine is unavailable (limited evidence)
Dosage and Administration
For Severe Hypoglycemia:- Adults and pediatric patients ≥25 kg: 1 mg subcutaneous, intramuscular, or intravenous
- Pediatric patients <25 kg: 0.5 mg (or 20-30 mcg/kg) subcutaneous, intramuscular, or intravenous
- May repeat in 15 minutes if no response
- Adults: 0.2-0.5 mg IV immediately prior to procedure
- Pediatric: 0.025-0.1 mg IV (not to exceed 0.5 mg)
- Use provided diluent (typically 1 mL of sterile water)
- Gently swirl until completely dissolved; do not shake vigorously
- Use immediately after reconstitution
- Hepatic impairment: Use with caution; reduced glycogen stores may diminish response
- Renal impairment: No dosage adjustment required
- Geriatric patients: Standard dosing recommended
- Pregnancy: Category B; use if clearly needed
- Lactation: Exercise caution; unknown if excreted in human milk
Pharmacokinetics
Absorption: Rapidly absorbed after IM or SC administration; onset of action within 10-15 minutes Distribution: Primarily distributed to liver, kidney, and gastrointestinal tract; minimal plasma protein binding Metabolism: Extensive metabolism in liver, kidney, and plasma Elimination: Half-life approximately 8-18 minutes; cleared by proteolytic enzymes in plasma and tissues Onset of Action:- IV: 1 minute
- IM: 8-10 minutes
- SC: 10-15 minutes
Contraindications
- Hypersensitivity to glucagon or any component of formulation
- Pheochromocytoma
- Insulinoma
- Glucagonoma
- Known lack of hepatic glycogen stores (starvation, chronic hypoglycemia, adrenal insufficiency)
Warnings and Precautions
- Hypoglycemia: May cause rebound hypoglycemia after initial hyperglycemic effect
- Gastrointestinal Effects: May cause nausea and vomiting, increasing aspiration risk in unconscious patients
- Cardiac Effects: Use with caution in patients with cardiac disease; may increase myocardial oxygen demand
- Hypersensitivity Reactions: Although rare, anaphylactoid reactions have been reported
- Ineffectiveness: Will not work in patients with depleted hepatic glycogen stores
- Pancreatic tumors: Contraindicated in patients with insulinoma or glucagonoma
Drug Interactions
- Beta-blockers: Glucagon may be used to treat overdose, but may have additive hyperglycemic effects
- Indomethacin: May blunt hyperglycemic effect of glucagon
- Anticholinergic agents: Additive effects on gastrointestinal motility inhibition
- Warfarin: Glucagon may enhance anticoagulant effect
- Insulin: Antagonistic effect; glucagon counteracts insulin's hypoglycemic action
Adverse Effects
Common (≥1%):- Nausea (most common)
- Vomiting
- Headache
- Dizziness
- Injection site reactions
- Hypersensitivity reactions (rash, urticaria, respiratory distress)
- Hypertension
- Tachycardia
- Hypoglycemia (rebound effect)
- Hypokalemia
Monitoring Parameters
- Blood glucose levels before, during, and after administration
- Vital signs (blood pressure, heart rate)
- Signs of hypersensitivity reactions
- Electrolytes (particularly potassium)
- Level of consciousness in hypoglycemic patients
- Gastrointestinal motility in diagnostic use
Patient Education
- Recognize signs and symptoms of severe hypoglycemia (confusion, seizures, unconsciousness)
- Proper storage and reconstitution technique
- Administration technique for caregiver education
- Importance of seeking emergency medical attention after administration
- Have a fast-acting carbohydrate source available after regaining consciousness
- Rotate injection sites to prevent lipodystrophy
- Discard any unused portion after reconstitution
- Carry medical identification indicating diabetes diagnosis
- Inform all healthcare providers about diabetes status
References
1. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2023;46(Suppl 1) 2. Glucagon Prescribing Information. US Food and Drug Administration 3. Seaquist ER, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association. Diabetes Care. 2013;36(5) 4. Cryer PE. Hypoglycemia in diabetes. Diabetes Care. 2014;37(5) 5. Pontiroli AE, et al. Glucagon administration and glucose metabolism in humans. Endocr Rev. 2021;42(5) 6. Pearson T. Glucagon as a therapeutic agent in hypoglycemia. Curr Diabetes Rev. 2019;15(2) 7. US National Library of Medicine. Glucagon - Drug Information. MedlinePlus 8. Micromedex Solutions. Glucagon Drug Monograph. Truven Health Analytics