Glucagon

What is glucagon?

Glucagon is a 29-amino-acid peptide hormone made by the alpha cells of the pancreas from the proglucagon gene. It is also an approved prescription medicine, first approved by the FDA in 1960. Modern products contain recombinant (rDNA) glucagon; older products were extracted from animal pancreas.

Identity

Glucagon should not be confused with:

• Dasiglucagon (Zegalogue), a separate glucagon analogue with its own INN, several amino-acid substitutions for stability in solution, and its own label.
• GLP-1 and GLP-2 (glucagon-like peptides, such as native GLP-1), which are different molecules.
• Glucagon-receptor co-agonists such as retatrutide, survodutide, mazdutide, pemvidutide and cotadutide, which are investigational drugs that include glucagon-receptor activity among other actions.
• Homeopathic products named "Glucagon" listed in DailyMed, which do not contain pharmacologically active glucagon.

How it works

Glucagon raises blood glucose mainly by releasing glucose from glycogen stored in the liver (hepatic glycogenolysis). Because it depends on those stores, the labels warn that it may not work when glycogen is depleted — for example in starvation, adrenal insufficiency or chronic hypoglycaemia. In some products, its relaxing effect on the smooth muscle of the gut is used to temporarily inhibit gastrointestinal motility during radiological examinations.

Approved uses and evidence

• Severe hypoglycaemia in diabetes: Baqsimi is approved for adults and children from 1 year, and Gvoke from 2 years; generic glucagon for injection is also approved for this use (labels).
• Diagnostic aid in radiology: generic glucagon for injection and Gvoke VialDx (adults) are approved as a diagnostic aid. The Fresenius Kabi product is approved for diagnostic use only and is "not indicated for the treatment of hypoglycemia" (labels). Published clinical data on this use are small (Pacchioni 1995); the labels are the primary source.

In a randomised crossover non-inferiority trial in adults with type 1 diabetes and insulin-induced hypoglycaemia, treatment success was 98.7% with intranasal glucagon versus 100% with intramuscular glucagon, with median times to success of 16 versus 13 minutes; head and facial discomfort was more common with the nasal form (25% vs 9%) (Rickels 2016). A phase 3 trial in Japanese patients compared the same forms (Matsuhisa 2020), and a phase 1 study described nasal glucagon in children and adolescents (Sherr 2016). A ready-to-use liquid glucagon autoinjector was non-inferior to the classic emergency kit and took less time to prepare (27 vs 97 seconds) (Christiansen 2021), and a further phase 3 trial compared room-temperature liquid glucagon with lyophilised glucagon (Pieber 2022).

Regulatory status

Generic glucagon for injection is marketed under several ANDAs. Drugs@FDA gives no reason for the discontinued Lilly and Novo Nordisk applications. In the EU, Baqsimi was centrally authorised in 2019 and Ogluo (the EU name for the Gvoke ready-to-use solution) in 2021; GlucaGen is nationally authorised.

Warnings and precautions

Current FDA labels carry no boxed warning. The labels list:

• Phaeochromocytoma: contraindicated because of the risk of a marked rise in blood pressure.
• Insulinoma: contraindicated because of the risk of rebound hypoglycaemia.
• Serious hypersensitivity and known hypersensitivity to the product.
• Lack of effect when glycogen stores are depleted (starvation, adrenal insufficiency, chronic hypoglycaemia).
• Injectable labels also mention hypoglycaemia in glucagonoma, necrolytic migratory erythema with continuous infusion, hyperglycaemia when used diagnostically in people with diabetes, and increases in blood pressure and pulse in people with heart disease.

Glucagon and weight-loss claims

Glucagon itself is not approved for weight loss, and no source reviewed here supports vendor claims that "research glucagon" causes weight loss or improves performance. The weight-loss results often mentioned alongside glucagon come from investigational co-agonists that combine glucagon-receptor activity with GLP-1 or GIP activity (for example retatrutide) — they do not apply to glucagon. Its use in beta-blocker or calcium-channel-blocker poisoning is off-label and not part of the labels; this page gives no protocol for it.

Dasiglucagon

Dasiglucagon (Zegalogue) is a separate, stabilised glucagon analogue with its own INN, PubChem record and label. It is covered on its own page and is not a redirect to glucagon.

Dosing

No dose is given here. Doses depend on the product, route and age and are defined only by the official prescribing information — see the Baqsimi FDA label on DailyMed (opens in a new tab) and the other labels in the references.

Claims vs evidence

Related pages

Dasiglucagon, Native GLP-1, Pramlintide, Retatrutide, Survodutide, Mazdutide, Pemvidutide, Cotadutide, Incretin axis.