Glucagon

Overview

Glucagon is a 29-amino-acid peptide hormone produced by the alpha cells of the pancreatic islets. It acts as the body's primary counter-regulatory hormone to insulin, raising blood glucose when levels fall too low. Pharmaceutical glucagon is FDA-approved for the emergency treatment of severe hypoglycemia, a situation in which a person cannot safely swallow food or drink because of confusion, unconsciousness, or seizure.

Several formulations exist. Injectable products such as GlucaGen historically required reconstitution from a powder, while newer ready-to-use auto-injectors and pen devices simplify administration during an emergency. Baqsimi is a nasal powder that delivers glucagon through the lining of the nose without an injection, which can make treatment easier for a frightened family member or bystander to give.

Beyond rescue therapy, glucagon-receptor agonism has become an area of interest in metabolic drug development. Some dual and triple incretin agents combine activity at the glucagon receptor with GLP-1 and GIP receptor activity, aiming to influence energy expenditure and metabolism. Those investigational combination drugs are distinct from the single-hormone rescue products discussed here.

How it works

Glucagon binds to the glucagon receptor, a G-protein-coupled receptor found mainly in the liver. Activation raises intracellular cyclic AMP, which triggers two key processes: glycogenolysis, the breakdown of stored glycogen into glucose, and gluconeogenesis, the synthesis of new glucose. The net effect is a rapid release of glucose from the liver into the bloodstream.

Because this mechanism depends on adequate liver glycogen stores, glucagon works best in people who have reserves to mobilize. Its effect may be blunted in individuals who are malnourished, have been fasting for an extended period, have advanced liver disease, or have depleted glycogen through heavy alcohol use. In those settings, glucose given by another route may be necessary.

Glucagon also relaxes smooth muscle and can transiently increase heart rate, properties that underlie some off-label and specialty uses. After administration, blood glucose typically begins to rise within minutes, but the effect is temporary. Once a person is alert enough to swallow, fast-acting carbohydrate followed by a longer-acting snack helps prevent glucose from falling again as the glucagon wears off.

Clinical evidence

Glucagon has a long history of clinical use, and its approval rests on its established ability to reverse severe hypoglycemia. Clinical studies of the various formulations have focused on whether each product reliably raises glucose to a safe level within a clinically meaningful window and how successfully caregivers can administer it under realistic conditions.

Comparative work on the nasal formulation examined whether intranasal delivery achieves glucose recovery comparable to injectable glucagon, including in usability studies where untrained or minimally trained people attempted to give a simulated dose. These studies are relevant because real-world rescue is often performed by a relative or colleague rather than a clinician, and ease of correct use can determine whether treatment succeeds.

It is important to be honest about the limits of the evidence. The peptide is well characterized for short-term rescue, but it is not a treatment for the underlying cause of recurrent hypoglycemia. Investigations of glucagon-receptor agonism within multi-receptor metabolic drugs are a separate and evolving field, and conclusions from those programs should not be generalized to the rescue products.

Dosing & side effects

Glucagon for severe hypoglycemia is administered as a single emergency dose by injection or, for the nasal product, into one nostril. This guide does not provide dose amounts; the correct product, route, and quantity are determined by the prescribing clinician and printed in the device instructions, which caregivers should review in advance. After giving glucagon, emergency services should generally be contacted, and the person should be turned on their side in case of vomiting.

The most common side effects are nausea and vomiting, which can occur after both injectable and nasal forms. The nasal product may additionally cause nasal or throat discomfort, watery eyes, and sneezing related to local delivery.

Glucagon should be used with caution or avoided in people with certain rare tumors, such as pheochromocytoma or insulinoma, where it could provoke harmful responses. Once the person recovers enough to eat, oral carbohydrate is needed to restore liver glycogen and reduce the risk of glucose dropping again. Any severe hypoglycemic event warrants follow-up to review its cause and adjust ongoing diabetes management.

Legal status

Glucagon products such as GlucaGen and Baqsimi are approved prescription medicines in the United States and many other countries. They are dispensed by pharmacies on the authorization of a licensed prescriber and are not available over the counter. Because they are intended for emergencies, prescriptions are often written so that a supply can be kept at home, school, or work and used by a trained caregiver.

Glucagon is not a controlled substance and carries no scheduling restrictions related to abuse potential. Regulatory oversight instead focuses on manufacturing quality, correct labeling, device usability, and appropriate storage, since an expired or improperly stored product may not work when it is needed most.

People who are prescribed glucagon, and those who live or work with them, are encouraged to learn how and when to use it before an emergency arises. Insurance coverage, product availability, and the specific approved formulations vary by region and over time, so a pharmacist or prescriber is the best source for current local information.

Frequently asked questions

References

Each source links to its original record — peer-reviewed studies, regulator pages, or reference texts, labelled by type. We summarize findings neutrally; a citation is a reference, not an endorsement, and not a claim that its authors reviewed this page.

1. Muller TD, Finan B, Clemmensen C, DiMarchi RD, Tschop MH. The New Biology and Pharmacology of Glucagon. Physiol Rev. 2017. Peer-reviewed study
2. Rickels MR, Ruedy KJ, Foster NC, et al. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care. 2016. Peer-reviewed study
3. Kajani S, Laker RC, Ratkova E, et al. Hepatic glucagon action: beyond glucose mobilization. Physiol Rev. 2024. Peer-reviewed study
4. Wewer Albrechtsen NJ, Holst JJ, Cherrington AD, et al. 100 years of glucagon and 100 more. Diabetologia. 2023. Peer-reviewed study
5. Neumann J, Hofmann B, Dhein S, et al. Glucagon and Its Receptors in the Mammalian Heart. Int J Mol Sci. 2023. Peer-reviewed study
6. Kleinert M, Sachs S, Habegger KM, et al. Glucagon Regulation of Energy Expenditure. Int J Mol Sci. 2019. Peer-reviewed study