Generic Name

Glucagon

Mechanism

• Glucagon is a 29‑amino‑acid peptide that activates the Gs‑coupled glucagon receptor (GCGR) primarily on hepatocytes.
• Binding stimulates adenylate cyclase, raising intracellular cAMP → activation of protein kinase A (PKA).
• PKA phosphorylates key enzymes:
• Glucose‑6‑phosphatase → promotes glycogenolysis and gluconeogenesis.
• Acetyl‑CoA carboxylase (ACC) → inhibits fatty acid synthesis, stimulating lipolysis.
• Net effect: rapid ↑ serum glucose (~5–8 mmol/L in 5–20 min) and lipolytic/thermogenic activity.

Pharmacokinetics

• Bioavailability: Injection route only.
• Intravenous (IV): 100 % bioavailability.
• Subcutaneous (SC) / Intramuscular (IM): ~70 % due to variable absorption.
• Distribution: Volume of distribution ~1 L/m²; modest tissue penetration.
• Metabolism: Peptidic degradation by serum peptidases, predominantly in the liver and kidneys.
• Elimination half‑life:
• Traditional glucagon: ~5–10 min (IV).
• Pegylated glucagon (e.g., Gvoke™): ~3‑4 h.
• Clearance: Mostly hepatic; renal excretion minimal.

Indications

• Severe hypoglycemia in adults and children, especially when standard glucagon kits are unavailable.
• Euglycemic clamp studies to confirm glucagon deficiency.
• Diagnostic testing for glucagonoma (exogenous glucagon detection).
• Pegylated glucagon (Gvoke™) for acute management of insulin‑induced hypoglycemia with a longer‑acting profile.

Contraindications

• Absolute contraindication: Known hypersensitivity to glucagon or any component of the formulation.
• Relative warnings:
• Severe hepatic disease – altered metabolism may prolong action.
• Cardiovascular disease – rapid glucose rise can precipitate arrhythmias in susceptible patients.
• Pregnancy & lactation – no definitive data; use only if benefits outweigh risks.
• Precautions: Monitor for hypotension or tachycardia; use cautiously in patients on beta‑blockers.

Dosing

• Reconstitution: 7 mL of sterile water → 1 mg vial; gently mix no more than 10 min.
• Auto‑injector use: Primed, check injection depth (IM vs. SC).
• Storage: Keep refrigerated (2–8 °C) or frozen (≤ –10 °C) until 30 days prior to use; thaw at room temperature before reconstitution.

Adverse Effects

• Common (≤ 10 %)
• Nausea, vomiting, diaphoresis.
• Hyperglycemia, transient hyperosmolarity.
• Injection site pain, erythema.
• Serious (≤ 1 %)
• Severe hypotension, tachycardia, arrhythmias.
• Hypersensitivity reactions: rash, angioedema.
• Hyperglycemia leading to diabetic ketoacidosis (rare in non‑diabetics).

Monitoring

• Blood glucose: Every 5–10 min during IV infusion until above 70 mg/dL; then every 30 min until stable.
• Hemodynamics: Heart rate, BP, ECG in patients with cardiac disease.
• Serum lactate: If lactic acidosis suspected.
• Post‑treatment glucose: 2–4 h after SC/IM to detect rebound hypoglycemia.

Clinical Pearls

• Use the 1 mg vial for rapid stabilization, but prefer the auto‑injector for out‑of‑hospital settings; the ABS (American Society of Clinical Oncology) recommends SC auto‑injectors for patients with type 1 diabetes in hypoglycemic emergencies.
• Reconstitute slowly and gently: vigorous shaking can denature the peptide.
• Do not dilute with glucose solutions; otherwise, the glucagon precipitates, reducing efficacy.
• Pegylated glucagon offers ~4‑fold longer duration, useful when frequent monitoring is not possible (e.g., in pediatric wards).
• Always have an insulin dose calculator handy: avoid over‑correction after glucagon; upper limit 3 IU/kg insulin if glucose remains >250 mg/dL.
• Adjunctive: If severe hypoglycemia persists after glucagon, add IV dextrose 50% to ensure adequate glucose delivery.

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• References: FDA label, UpToDate® “Glucagon for Hypoglycemia”, Endocrine Society guideline on glucagon use.