Glucagon

Endogenous peptide hormone used in medicine primarily for (1) emergency treatment of severe hypoglycemia when IV dextrose is delayed or impossible, and (2) high-dose IV therapy as an antidote in beta-blocker and calcium channel blocker overdose. Also used as an adjunct in refractory anaphylaxis in patients on beta-blockers.

For hypoglycemia in the field/ward: Adult and larger pediatric patients typically receive 1 mg IM, SC, or IV; smaller children receive 0.5 mg (or 0.02–0.03 mg/kg). Intranasal Baqsimi delivers 3 mg into one nostril for patients ≥1 year old.

In beta-blocker or calcium channel blocker overdose: An initial IV bolus of 50 mcg/kg (≈3–5 mg in adults) followed by an infusion (e.g., 2–5 mg/hour, up to ~10 mg/hour) is commonly recommended in toxicology resources, titrated to heart rate and blood pressure response.

Mechanism: Activates glucagon (Gs-coupled) receptors in the liver → glycogenolysis and gluconeogenesis (raising blood glucose), and in the heart → increased intracellular cAMP independent of β-adrenergic receptors, producing positive inotropy and chronotropy even in the presence of beta-blockade.

Onset for hypoglycemia: IV onset within ≈1 minute; IM/SC onset ≈5–15 minutes; intranasal onset about 10–15 minutes. Duration of hyperglycemic effect is typically 1–2 hours, dependent on hepatic glycogen stores.

• Generic Name: Glucagon (recombinant human, various formulations)
• Brand Names: GlucaGen, Gvoke, Baqsimi, Zegalogue (US), plus multiple generics – availability is region- and institution-specific

Peptide hormone; antihypoglycemic agent; antidote (beta-blocker/CCB toxicity); positive inotrope/chronotrope via non–β-adrenergic pathway

Mechanism of Action:

• Glucagon is a 29–amino acid peptide hormone that binds to the glucagon receptor, a Gs protein–coupled receptor present mainly on hepatocytes and cardiomyocytes
• Hepatic effects: Gs activation stimulates adenylyl cyclase → increased cAMP → activation of protein kinase A → stimulation of glycogenolysis and gluconeogenesis, raising blood glucose. This requires adequate hepatic glycogen stores
• Cardiac effects: In the heart, glucagon receptor activation raises cAMP independent of β-adrenergic receptors, increasing intracellular calcium and producing positive inotropic and chronotropic effects. This mechanism explains its use in beta-blocker and calcium channel blocker toxicity and in refractory anaphylaxis in beta-blocked patients
• GI effects: Glucagon relaxes smooth muscle of the gastrointestinal tract and transiently decreases motility; this is exploited in some radiologic procedures and historically for esophageal food impaction (efficacy variable)

Pharmacokinetics:

• Formulations/routes: Powder for reconstitution for IM/SC/IV injection (1 mg vials or prefilled devices), prefilled SC autoinjectors/syringes (e.g., Gvoke 0.5 mg and 1 mg), intranasal powder (Baqsimi 3 mg), and diagnostic IV formulations for radiology
• Onset of action: IV – within ~1 minute; IM/SC – typically 5–15 minutes; intranasal – around 10–15 minutes
• Duration of hyperglycemic effect: Usually 60–90 minutes (range 1–2 hours), depending primarily on hepatic glycogen stores and concurrent insulin levels
• Distribution: Small volume of distribution (~0.2–0.3 L/kg); plasma protein binding is minimal
• Metabolism: Glucagon is rapidly degraded by proteases in the liver, kidney, and plasma
• Elimination half-life: About 3–6 minutes in healthy individuals, but physiologic effects persist longer due to downstream signaling and hepatic glycogen mobilization
• Renal or hepatic impairment can alter clearance and responsiveness; clinical effect may be blunted in advanced liver disease due to reduced glycogen

• Emergency treatment of severe hypoglycemia (with unconsciousness, seizure, or inability to take oral carbohydrates) in patients with diabetes when IV access or IV dextrose is not immediately available (IM, SC, or intranasal)
• Hospital treatment of severe hypoglycemia when rapid IV dextrose cannot be administered or as a bridge while access is obtained
• High-dose IV therapy as an antidote in suspected or proven beta-blocker overdose with bradycardia, hypotension, or cardiogenic shock (often as an initial temporizing measure before high-dose insulin therapy and vasopressors)
• Adjunct high-dose IV therapy in calcium channel blocker overdose with hypotension or bradycardia (evidence less robust than for beta-blocker toxicity)
• Adjunct in refractory anaphylaxis in patients receiving beta-blockers (e.g., poor response to epinephrine) to provide non–β-adrenergic inotropy/chronotropy
• Diagnostic aid for GI radiologic procedures and other niche radiology uses (less relevant to EMS/ED, but worth knowing)

Available Forms:

• Traditional emergency kits (e.g., GlucaGen): 1 mg lyophilized glucagon powder with diluent for IM/SC/IV injection after reconstitution
• Prefilled SC autoinjectors and prefilled syringes (e.g., Gvoke): 0.5 mg/0.1 mL and 1 mg/0.2 mL for subcutaneous use
• Intranasal glucagon (Baqsimi): 3 mg single-use intranasal device for adults and children ≥1 year of age
• Diagnostic IV formulations (vials) for radiology use, with dosing per procedure protocol
• Always confirm product, route, and strength before administration; formulations intended only for SC use should not be used IV

Dosing – Severe Hypoglycemia (Emergency Use):

Dosing – High-Dose IV Glucagon (Beta-Blocker / CCB Overdose, Refractory Anaphylaxis):

Additional Dosing Notes:

• For hypoglycemia, glucagon is not a substitute for definitive carbohydrate replacement. Once the patient is awake and able to swallow, give oral carbohydrates; in hospital, follow with IV dextrose as appropriate
• Glucagon is less effective in patients with depleted hepatic glycogen (e.g., prolonged fasting, alcoholism, adrenal insufficiency, severe liver disease). In these cases, IV dextrose is preferred and may be the only effective therapy
• High-dose IV glucagon for overdose frequently causes severe nausea and vomiting; pre-treat with antiemetics and be prepared to protect the airway
• In beta-blocker/CCB overdose, glucagon is adjunctive therapy; high-dose insulin euglycemia therapy and vasopressors are often more important for sustained improvement. Always involve a poison control center or toxicologist
• For all high-dose indications, dosing ranges vary across references; always follow local toxicology protocols and consult poison control

Contraindications:

• Known hypersensitivity to glucagon or formulation components
• Pheochromocytoma – glucagon can precipitate massive catecholamine release, leading to severe hypertension and arrhythmias
• Insulinoma – glucagon may cause initial hyperglycemia followed by exaggerated insulin release and recurrent hypoglycemia

Major Precautions:

• Chronic hypoglycemia, prolonged fasting, malnutrition, adrenal insufficiency, or severe hepatic disease: Reduced glycogen stores limit glucagon efficacy
• Cardiovascular disease: Glucagon's inotropic and chronotropic effects can provoke tachycardia, hypertension, or ischemia; monitor closely, especially in patients with coronary artery disease or arrhythmias
• Pregnancy and lactation: Widely used for hypoglycemia rescue when needed; no strong evidence of teratogenicity, but severe hypoglycemia itself is harmful—treat promptly
• Use in children: Follow weight-based dosing and pediatric hypoglycemia guidelines; monitor closely for vomiting and airway compromise
• Sulfonylurea-induced hypoglycemia: Glucagon alone may be insufficient or temporary; dextrose infusion and sometimes octreotide are required

Common:

• Nausea and vomiting (very common, dose-related)
• Transient tachycardia and palpitations
• Mild hypertension or hypotension
• Headache and dizziness
• Injection-site discomfort with IM/SC dosing; nasal irritation with intranasal formulations

Serious:

• Severe vomiting with risk of aspiration, particularly in unprotected airways or patients with altered mental status
• Significant hypertension and arrhythmias in patients with pheochromocytoma or severe cardiovascular disease
• Rebound hypoglycemia in patients with insulinoma or sulfonylurea overdose if not followed by carbohydrate and definitive therapy
• Hypersensitivity reactions, including anaphylaxis (rare)

• Blood glucose before and after dosing (and serially every 15–30 minutes initially) until stable and definitive carbohydrate therapy is given
• Level of consciousness, seizure activity, and ability to protect airway; position unconscious patients on their side to reduce aspiration risk after IM/IN dosing
• Heart rate, blood pressure, and rhythm, especially when using high-dose IV glucagon for overdose or anaphylaxis
• Electrolytes (especially potassium) and metabolic panels in overdose contexts, as glucagon and accompanying therapies (e.g., insulin) can alter glucose and potassium
• For ongoing high-dose infusions, monitor for persistent vomiting, hemodynamic response, and development of ischemia or arrhythmias

• Morris, C. H., & Gabriele, A. (2024). Glucagon. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK559195/
• DrugBank Online. (2024). Glucagon (DB00040). DrugBank. https://go.drugbank.com/drugs/DB00040
• U.S. Food and Drug Administration. (2025). BAQSIMI (glucagon) nasal powder 3 mg prescribing information. DailyMed / FDA label.
• U.S. Food and Drug Administration. (2024). GVOKE (glucagon) injection prescribing information. DailyMed / FDA label.
• Khalid, M. M., et al. (2023). Beta-blocker toxicity. In StatPearls [Internet]. StatPearls Publishing.