Glucagon: Effect in Hypoglycemia and Emergency
Glucagon is an endogenous peptide hormone of the alpha cells of pancreatic islets and the main antagonist of insulin. In metabolism, it regulates glycogen release from the liver and stabilizes blood sugar between meals. As a medication, glucagon (brand names GlucaGen and generics, new intranasal form Baqsimi) is established in emergency treatment of severe hypoglycemia. Beyond this, it has specialized applications in endoscopy, cardiology for beta blocker or calcium antagonist poisoning, and in diagnostics.
Its use in hypoglycemia emergencies is particularly important for relatives and friends of people with type 1 diabetes mellitus. When the affected person is no longer responsive and cannot take glucose orally, glucagon is a life-saving option to raise blood sugar rapidly. The intranasal form has reduced application anxiety in recent years because injection is no longer required.
Mechanism of Action
Glucagon binds to the glucagon receptor, a Gs coupled receptor on hepatocytes, cardiac muscle cells, and smooth muscle. Activation leads to increased cAMP and thus activation of protein kinase A. In the liver, glycogen phosphorylase is activated and glycogen synthase is inhibited, so glycogen is rapidly broken down to glucose and released into the bloodstream. Additionally, gluconeogenesis and lipolysis are stimulated.
In the heart, glucagon exerts a positive inotropic and positive chronotropic effect that is independent of beta adrenoreceptors. This property makes glucagon an established antidote option for beta blocker and, to a lesser extent, calcium antagonist poisoning. On smooth muscle of the gastrointestinal tract, glucagon acts spasmolytically and is therefore used in endoscopy and radiology, for example in examinations of the upper gastrointestinal tract or to reduce peristaltic movement in MRI.
The half-life of glucagon is only about three to six minutes. Breakdown occurs enzymatically in the liver and kidneys. Because of the short duration of action, repeated administration or accompanying oral glucose intake is important in hypoglycemia once the patient becomes responsive.
Areas of Use
- Severe hypoglycemia in unconscious or altered consciousness patients with diabetes, especially under insulin therapy, intramuscularly, subcutaneously, or intranasally
- Beta blocker poisoning with marked bradycardia and hypotension, intravenously as a bolus followed by infusion
- Calcium antagonist poisoning, adjunctive to other therapy
- Endoscopy and radiology to inhibit gastrointestinal peristalsis, especially during gastroscopy, ERCP, and MRI of abdominal organs
- Diagnostic tests, such as in suspected pheochromocytoma
- Adjuvant in pediatrics in children with hypoglycemia under diabetes therapy or rare metabolic disorders
Glucagon does not replace professional emergency care in hypoglycemia. If altered consciousness persists, there is no response, or episodes recur, the emergency service must be called.
Dosage and Administration
Severe hypoglycemia adults: 1 mg subcutaneously or intramuscularly. If no improvement after 10 to 15 minutes, a second dose may be given. Once the patient becomes responsive, administer oral carbohydrates (juice, glucose gel, meal), because glucagon has only brief effect and liver glycogen reserves may be limited.
Intranasal (Baqsimi): 3 mg sprayed into one nostril, no deep inhalation required. Can be used even in unconscious persons.
Pediatric: Children under 25 kg 0.5 mg subcutaneously or intramuscularly, older children 1 mg. Intranasal form from defined age threshold according to prescribing information.
Beta blocker poisoning: initially 5 to 10 mg intravenously as a bolus, followed by continuous infusion 2 to 5 mg per hour, depending on clinical condition. Concomitant volume administration, vasopressors, possibly high-dose insulin glucose regimen.
Endoscopy and radiology: 0.2 to 1 mg intravenously or intramuscularly shortly before examination. Onset of action is rapid, duration of effect is several minutes.
Renal insufficiency and hepatic insufficiency: no relevant adjustment in emergency use. In chronic liver disease, efficacy may be reduced because liver glycogen reserves are limited.
Side Effects
Frequent: nausea, vomiting, headache, transient tachycardia, rebound hypoglycemia after effect wears off.
Occasional: allergic skin reactions, local reaction at injection site, intranasal sneezing, eye tearing, nasal mucosa irritation.
Rare but relevant: anaphylaxis, hyperkalemia, marked hyperglycemia after high dose in patients without hypoglycemia.
In pheochromocytoma: possible triggering of hypertensive crisis because glucagon stimulates catecholamine release.
Rebound hypoglycemia: blood sugar may drop again after the effect wears off. Therefore oral carbohydrates and a meal after regaining consciousness, possibly hospital observation.
Drug Interactions
- Insulin and oral antidiabetics: opposing effects, in acute hypoglycemia the effect of glucagon is important despite ongoing therapy.
- Beta blockers: glucagon is an antidote at higher doses, lower doses are less effective for beta blocker associated bradycardias.
- Vitamin K antagonists (warfarin, phenprocoumon): glucagon may theoretically enhance anticoagulation, clinically rarely relevant in acute use.
- Indomethacin: may reduce the hyperglycemic effect of glucagon.
- Anticholinergics: in endoscopy alternative spasmolytic options, combined use rare.
Special Notes
Pregnancy: use is possible when vitally indicated for severe hypoglycemia because the risk of hypoglycemia to mother and fetus clearly outweighs the possible risk of the active substance. Breastfeeding: transfer into breast milk is clinically not relevant because oral ingestion by the infant produces minimal systemic effect.
Children: established in pediatric diabetology.
Pheochromocytoma, insulinoma: contraindications because paradoxical reactions may occur.
Training: relatives and close caregivers of people with type 1 diabetes should be trained in the use of glucagon, ideally as part of diabetes education. The intranasal form significantly lowers the application barrier.
Storage: powder with solvent in dual chamber cartridges, refrigeration according to prescribing information, check expiration date, keep multiple emergency kits in important locations (home, workplace, car).
After acute treatment: oral carbohydrates, medical reevaluation of diabetes therapy, adjustment of insulin doses, identification of triggering factors such as exercise, meal timing errors, alcohol.
Driving ability: after hypoglycemia and glucagon emergency, driving should be avoided for at least several hours because cognitive functions are often not yet fully restored.
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Frequently Asked Questions
When do I use glucagon?
In severe hypoglycemia when the affected person is no longer able to safely drink or eat, for example with altered consciousness, seizure, or unconsciousness. Prior training of family members is important to respond correctly in the acute situation. Once the patient becomes responsive, oral carbohydrates are essential.
Does glucagon work with alcohol consumption?
In alcohol-induced hypoglycemia, liver glycogen reserves are often depleted and glucagon is ineffective. In this case, intravenous glucose via emergency service is the safer option. Also with prolonged fasting or severe liver disease, glucagon may be less effective.
What happens after glucagon administration?
Blood sugar rises rapidly and the person becomes responsive again. The effect lasts several minutes to at most one hour. Therefore oral carbohydrates, a meal, observation. Rebound hypoglycemia is possible, so in type 1 diabetes mellitus patients are monitored further in the hospital.
Do I need glucagon for hypoglycemia in type 2 diabetes?
Not routinely, because severe hypoglycemia is rare under typical type 2 therapy. With intensified insulin therapy or sulfonylureas with risk of severe hypoglycemia, an emergency kit may be appropriate. The indication is determined individually by the diabetes care team.
Sources
- Gelbe Liste, Glucagon active ingredient profile
- BfArM, Federal Institute for Drugs and Medical Devices
- AWMF, Guidelines for Type 1 Diabetes Mellitus and Hypoglycemia
- German Diabetes Society
Legal Notice and Disclaimer
The information provided on this page is for general information purposes only and does not constitute medical advice, diagnosis, or treatment recommendation. It does not replace the advice of a licensed physician or pharmacist. Glucagon for emergency use should be part of comprehensive diabetes education with medical supervision. All information is based on prescribing information published at the time of preparation and recognized scientific sources, with the currently valid prescribing information of the manufacturer being authoritative. Sanoliste assumes no liability for completeness, currency, or accuracy of the information presented. In a medical emergency, call the emergency number 112.