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Reference material for UK healthcare professionals. Doses and licensing change — verify against the current SmPC and local policy before use.

Drug monographs / Glucagon

Glucagon

A hormone with a three-to-six-minute half-life, a licence covering hypoglycaemia and endoscopy, and a well-established emergency use that its own product label appears to prohibit.

AntidoteToxicologyEndocrineShockResuscitation

At a glance

ClassPancreatic α-cell hormone; Gs-coupled receptor agonist
Severe hypoglycaemia1 mg SC or IM (adult)
Children0.5 mg if <25 kg or under 6–8 years
OnsetResponse normally within 10 minutes
Half-life3–6 minutes
Beta-blocker overdoseOff-label — high dose, see below
Fails whenGlycogen depleted — alcohol, prolonged fasting, adrenal insufficiency
ContraindicatedPhaeochromocytoma; insulinoma caution

Why this drug is interesting

Glucagon is used in emergency medicine for two purposes that share almost nothing beyond the vial. The first is the reversal of severe hypoglycaemia — a licensed, well-evidenced, single-dose intervention that a paramedic or a family member can deliver. The second is the treatment of beta-blocker poisoning, which uses roughly ten times the dose, by a route and in a manner the product licence does not cover, on evidence that is thin.

The interesting part is the mechanism that connects them. Glucagon's receptor is Gs-coupled, so it raises intracellular cyclic AMP in cardiac myocytes without passing through the beta-adrenoceptor. That gives it an inotropic and chronotropic effect that a beta-blocker cannot antagonise — a pharmacological back door into a receptor system that has been locked.

Pharmacology

Mechanism

Glucagon is a 29-amino-acid polypeptide secreted by pancreatic α-cells. At the hepatic glucagon receptor it drives glycogenolysis and gluconeogenesis, raising blood glucose. In cardiac muscle it acts at the same Gs-coupled receptor to raise cAMP, producing positive inotropy and chronotropy that are independent of β-adrenoceptors — the property that makes it useful in beta-blockade.

It also relaxes smooth muscle throughout the gastrointestinal tract, which is the basis of its second licensed indication: motility inhibition for endoscopic and radiological examination.

Kinetics

Onset (SC/IM, hypoglycaemia)
Response normally within 10 minutes
Onset (IV, 0.2–0.5 mg, diagnostic)
Within 1 minute; duration 5–20 minutes
Onset (IM, 1–2 mg, diagnostic)
5–15 minutes; duration approximately 10–40 minutes
Half-life
3–6 minutes; liver and kidney each ~30% of clearance
Placental transfer
Does not cross the human placenta

Licensed indications and dosing

Severe hypoglycaemia

The licensed indication is "treatment of severe hypoglycaemic reactions, which may occur in the management of insulin treated children and adults with diabetes mellitus."1

  • Adults: 1 mg by subcutaneous or intramuscular injection
  • Children under 25 kg or younger than 6–8 years: 0.5 mg
  • Children above 25 kg or older than 6–8 years: 1 mg
  • No dose adjustment in the elderly, or in renal or hepatic impairment
  • The patient will normally respond within 10 minutes. If there is no response within 10 minutes, give intravenous glucose.

Inhibition of gastrointestinal motility (diagnostic)

  • Stomach, duodenal bulb, duodenum, small bowel: 0.2–0.5 mg IV, or 1 mg IM
  • Colon: 0.5–0.75 mg IV, or 1–2 mg IM
  • Safety and efficacy in children not established for this indication
  • Give oral carbohydrate afterwards if the procedure allows, particularly in a fasted patient

Beta-blocker and calcium channel blocker poisoning

The rationale

In beta-blocker overdose the β-adrenoceptor is occupied, so catecholamines are ineffective at achievable doses. Glucagon raises myocardial cAMP through its own receptor, bypassing the blockade entirely. That mechanism is sound, and in animal models the haemodynamic effect is real. The rationale is weaker in calcium channel blocker poisoning, where the lesion is downstream at the L-type channel — glucagon is sometimes tried, but high-dose insulin and calcium sit ahead of it.

The regimen in common use

  • A bolus of 5–10 mg IV in an adult (commonly quoted as 50–150 µg/kg), given over 1–2 minutes
  • Repeated if there is a haemodynamic response but it is not sustained
  • Followed, where a response is obtained, by an infusion titrated to effect — conventionally at the hourly rate that produced the response
  • Give an antiemetic. Vomiting at these doses is near-universal, and the patient's airway may already be compromised.

Contraindications, cautions and adverse effects

Contraindications

  • Hypersensitivity to glucagon or excipients
  • Phaeochromocytoma — glucagon stimulates catecholamine release, and in the presence of a phaeochromocytoma will provoke an acute hypertensive crisis

Cautions

  • Insulinoma — the SmPC advises caution, noting only that "glucagon reacts antagonistically towards insulin". The mechanism usually given for the hazard is that glucagon stimulates insulin release from the tumour, producing rebound hypoglycaemia; the label does not state this, so treat it as the conventional explanation rather than a labelled one
  • Glucagonoma — caution when used diagnostically
  • Cardiac disease — glucagon raises myocardial oxygen demand, blood pressure and heart rate; monitor and treat if indicated
  • Diabetes — short-term hyperglycaemia when used as a diagnostic aid

Interactions

Insulin
Directly antagonistic
Indomethacin
Glucagon may lose its ability to raise blood glucose, or paradoxically produce hypoglycaemia
Warfarin
Glucagon may increase the anticoagulant effect
Beta-blockers
A greater rise in pulse and blood pressure is expected — temporary, given the short half-life, but may need treatment in coronary disease. This is the interaction being exploited deliberately in overdose.

Adverse effects

  • Nausea — common (≥1/100); vomiting uncommon (≥1/1,000) and abdominal pain rare at licensed doses. At the doses used in poisoning, vomiting is the rule rather than the exception — but that is a dose effect, not the labelled frequency
  • Hypersensitivity reactions including anaphylaxis — very rare (<1/10,000)
  • Hypoglycaemia and hypoglycaemic coma when used diagnostically, especially in fasted patients
  • Tachycardia and blood pressure changes — reported with the diagnostic (endoscopic/radiographic) use
  • Hyperglycaemia and hypokalaemia at the high doses used in poisoning

Practical use in the ED

  1. In hypoglycaemia, glucose beats glucagon whenever you have a vein. Glucagon exists for the situation where you do not — prehospital, in a fitting patient, in a family member's hands. If a cannula is already in, use it.
  2. Ask about alcohol before you rely on glucagon. The overlap between severe hypoglycaemia and alcohol is substantial, and it is precisely the population in whom glucagon fails. Same for the malnourished and the patient with advanced liver disease.
  3. Then feed them. Oral carbohydrate after response is part of the drug's mechanism, not aftercare.
  4. In beta-blocker overdose, treat glucagon as a bridge. It buys minutes while high-dose insulin is prepared and takes effect — and high-dose insulin takes 30–45 minutes to work, which is exactly the gap glucagon is good at filling.
  5. Call NPIS early. Both the dose and the infusion are outside the licence, and the decisions get harder, not easier, as the case progresses.

Critical appraisal

  1. The hypoglycaemia indication is solid; the poisoning indication is not. Glucagon in beta-blocker overdose rests on animal studies and case reports. There is no randomised human evidence, and the effect in reported cases is frequently transient. It is reasonable to give it; it is not reasonable to expect it to be the treatment.
  2. The three-to-six minute half-life makes bolus therapy incoherent in poisoning. Any sustained haemodynamic effect requires an infusion, and the SmPC says the product is not stable enough to be infused. That contradiction has never been properly resolved — it is simply worked around in practice, and worth naming rather than glossing.
  3. Vomiting is under-weighted in most teaching. At 10 mg the emetic effect is close to universal, in a patient who may be obtunded from the poisoning itself. Airway protection and an antiemetic should be planned before the dose, not after the vomit.
  4. Its niche is genuinely narrow but genuinely real. A Gs-coupled inotrope that works through a receptor a beta-blocker cannot reach is not something else in the cupboard can do. The honest framing is a short-acting bridge with a supply problem, not a rescue.

References

  1. 1
    GlucaGen 1 mg / GlucaGen HypoKit 1 mg powder and solvent for solution for injection — Summary of Product Characteristics, Novo Nordisk. electronic Medicines Compendium. Sections 4.1–4.5, 4.8, 5.2. Verified 23 Aug 2026.
  2. 2
    St-Onge M, Anseeuw K, Cantrell FL, et al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Crit Care Med 2017;45(3):e306–15. PubMed
  3. 3
    Engebretsen KM, Kaczmarek KM, Morgan J, Holger JS. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin Toxicol 2011;49(4):277–83. PubMed
  4. 4
    TOXBASE — beta-blockers; glucagon. National Poisons Information Service. toxbase.org (NHS login required. NPIS: 0344 892 0111. The authoritative UK source for the off-label regimens described above.)
  5. 5
    Glucagon — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk

Last reviewed 2026-08-24 · Author: Dr Nirmalya Hore