Glucagon

The 29-residue pancreatic alpha-cell hormone that raises blood glucose through the hepatic glucagon receptor, FDA approved since 1960 as an injectable rescue for severe hypoglycemia and a radiologic diagnostic aid, and since 2019 as ready-to-use autoinjectors and a nasal powder.

Also referenced as: Glucagon hydrochloride, Glucagon for injection, Glucagon (rDNA origin), Recombinant glucagon, Nasal glucagon, Glucagon nasal powder, Baqsimi, LY900018, Gvoke, Gvoke HypoPen, Gvoke VialDx, GlucaGen, GlucaGen HypoKit, Glucagon Emergency Kit, Pancreatic glucagon

Also appears in: Metabolic

COA Public product evidence No certificate records are bound to a tracked Glucagon product page A record counts here only when a vendor publishes a certificate against one of its own tracked Glucagon product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

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What is Glucagon?

Glucagon is a 29-amino-acid peptide hormone (sequence HSQGTFTSDYSKYLDSRRAQDFVQWLMNT, about 3,483 Da) secreted by the alpha cells of the pancreatic islets. It is cut from the proglucagon precursor, the same gene product that intestinal L-cells process into GLP-1 and GLP-2, and its job in physiology is the mirror image of insulin’s: when blood glucose falls, glucagon tells the liver to release glucose. It was first noticed in 1923 as a hyperglycemic contaminant of early insulin extracts (Kimball and Murlin, Journal of Biological Chemistry, 1923), crystallized in 1955 (Staub et al., Journal of Biological Chemistry, 1955, 214(2):619–632), and sequenced in 1957 (Bromer et al., Diabetes, 1957, 6(3):234–238).

As a drug, glucagon has been FDA approved since 1960, originally as animal-sourced powder for injection, then as recombinant kits in 1998, and since 2019 as ready-to-use autoinjectors and a nasal powder for severe hypoglycemia in people with diabetes. It is also used intravenously or intramuscularly as a diagnostic aid to still the gut during radiologic examinations. The molecule matters beyond its own label: the glucagon receptor is the “glucagon” in the dual and triple agonists now in late development for obesity, which is the main reason the name shows up in research-peptide discussions.

How it works

Glucagon acts through the glucagon receptor (GCGR), a class B G-protein-coupled receptor expressed most densely on hepatocytes, with lower expression in kidney, heart, adipose tissue, and pancreatic islets.

• Receptor coupling — GCGR was expression-cloned from rat liver in 1993 and shown to couple to Gs-driven cAMP production, with a secondary calcium signal (Jelinek et al., Science, 1993, 259(5101):1614–1616). The crystal structure of the human receptor’s seven-transmembrane domain was solved in 2013 and explained how the peptide’s N-terminus reaches into the receptor core while its C-terminal helix docks on the extracellular domain (Siu et al., Nature, 2013, 499(7459):444–449)
• Hepatic glucose output — in the liver, cAMP activates protein kinase A, which switches on glycogen phosphorylase and switches off glycogen synthase, releasing glucose from glycogen within minutes; over hours, CREB- and PGC-1α-dependent transcription raises gluconeogenesis. The rescue effect depends on stored glycogen, which is why the labels warn of lack of efficacy in starvation, adrenal insufficiency, or chronic hypoglycemia (Müller et al., Physiological Reviews, 2017, 97(2):721–766)
• Beyond glucose — glucagon also stimulates hepatic fatty-acid oxidation and ketogenesis, drives amino-acid catabolism and ureagenesis (the liver–alpha-cell axis), raises energy expenditure, and reduces food intake; these effects, not glucose-raising, are what the obesity co-agonists try to recruit (Habegger et al., Nature Reviews Endocrinology, 2010, 6(12):689–697)
• Smooth muscle and the diagnostic indication — at pharmacologic doses glucagon relaxes gastrointestinal smooth muscle, producing the transient hypotonia radiologists use for barium studies, CT, and MR enterography; the same receptor pharmacology produces the positive inotropic and chronotropic cardiac effects noted in the labels. Mice lacking the receptor have lower glucose, marked hyperglucagonemia, and alpha-cell hyperplasia, which illustrates how tightly the liver feeds back on the alpha cell (Gelling et al., Proceedings of the National Academy of Sciences, 2003, 100(3):1438–1443)

Research status

Glucagon is a mature drug with a century of physiology behind it. The modern clinical literature is about delivery, not efficacy: reconstituting a lyophilized vial under stress fails often enough that the 2015–2021 trials were designed to show that easier formats are no worse than the kit.

Nasal glucagon (Baqsimi). Intranasal glucagon was first shown to raise glucose in healthy volunteers in 1983 (Pontiroli et al., British Medical Journal, 1983, 287(6390):462–463) but needed an absorption-enhanced dry powder to become practical. The pivotal adult study (NCT01994746) was a randomized crossover at eight centers in 75 adults with type 1 diabetes: after insulin-induced hypoglycemia, 3 mg nasal glucagon met the success criterion in 98.7% of visits versus 100% for 1 mg intramuscular glucagon, with mean time to success of 16 versus 13 minutes (Rickels et al., Diabetes Care, 2016, 39(2):264–270). A pediatric dose-ranging study in 48 children and adolescents aged 4 to under 17 found that all 24 intramuscular doses and 58 of 59 intranasal doses raised glucose by at least 25 mg/dL within 20 minutes (Sherr et al., Diabetes Care, 2016, 39(4):555–562). Prospective real-world studies of caregiver use during spontaneous hypoglycemic episodes reported resolution within 30 minutes in 95.7% of patients (157 events in 69 adults; Seaquist et al., Diabetes, Obesity and Metabolism, 2018, 20(5):1316–1320) and in all 33 pediatric events (14 patients; Deeb et al., Pediatric Diabetes, 2018, 19(5):1007–1013), and a simulated-rescue study found untrained bystanders delivered a full nasal dose far more often and faster than the injectable kit (Yale et al., Diabetes Technology & Therapeutics, 2017, 19(7):423–432). The FDA approved Baqsimi on July 24, 2019 for patients aged 4 and older; a March 2025 efficacy supplement extended the indication to age 1 and older on the basis of a small study in seven children under 4. The product was developed by Lilly and sold to Amphastar in 2023.

Ready-to-use liquid glucagon (Gvoke). Native glucagon is unstable and fibrillates in water, which is why kits ship as powder. Xeris dissolved it in dimethyl sulfoxide to make a shelf-stable liquid. Two Phase 3 crossover non-inferiority studies (NCT02656069, NCT03439072) in 161 adults with type 1 diabetes compared the autoinjector against the reconstituted kit; pooled treatment success was 98.7% versus 100% (Christiansen et al., BMJ Open Diabetes Research & Care, 2021, 9(1):e002137). The label reports a mean time to treatment success of 13.8 minutes versus 10 minutes for the kit, so the trade is a few minutes for a device that does not need mixing. Gvoke was approved September 10, 2019 for patients aged 2 and older, and on March 14, 2025 a supplemental application added Gvoke VialDx, an intravenous concentrate for the radiologic diagnostic-aid indication, which is distributed by American Regent under its own label.

Dasiglucagon (Zegalogue). Zealand Pharma’s analog substitutes seven residues to make a peptide that stays soluble in an aqueous autoinjector; it is covered on its own dasiglucagon profile. The FDA approved it on March 22, 2021 for severe hypoglycemia, and as of October 2026 Drugs@FDA lists no dasiglucagon approval beyond that NDA.

Generic and synthetic kits; the recombinant kits are gone. Lilly’s recombinant Glucagon Emergency Kit (NDA 020928, 1998) and Novo Nordisk’s recombinant GlucaGen HypoKit (NDA 020918, 1998) were the standard rescue products for two decades. Lilly withdrew its kit from the U.S. market in late 2022, and Novo Nordisk discontinued GlucaGen HypoKit in the U.S. in 2024, citing a kit-component supply problem; Drugs@FDA lists both applications as discontinued, with Federal Register determinations that neither was withdrawn for safety or effectiveness reasons. The kits still sold are synthetic peptide: Fresenius Kabi’s 505(b)(2) product (NDA 201849, May 2015), Amphastar’s first generic (ANDA 208086, December 28, 2020), and further generics from Mylan (December 2024), Lupin (July 2025), and Cipla (September 2025).

Low-dose and closed-loop uses. Small subcutaneous “mini-doses” from a reconstituted kit were described for impending hypoglycemia in children two decades ago (Haymond and Schreiner, Diabetes Care, 2001, 24(4):643–645), and Phase 2 trials have tested liquid mini-dose glucagon for mild hypoglycemia and exercise (NCT02081014, NCT02411578, NCT02660242). Glucagon and dasiglucagon are also the second hormone in bihormonal “bionic pancreas” systems; a 2021 report compared the insulin-only and bihormonal iLet in adults with type 1 diabetes (Castellanos et al., Diabetes Care, 2021, 44(6):e118–e120). No bihormonal pump has been approved in the United States.

The receptor in type 2 diabetes and obesity. Because glucagon is inappropriately high in diabetes (Unger and Cherrington, Journal of Clinical Investigation, 2012, 122(1):4–12), blocking it was an obvious idea. Lilly’s oral antagonist LY2409021 lowered HbA1c meaningfully over 24 weeks but raised alanine aminotransferase (Kazda et al., Diabetes Care, 2016, 39(7):1241–1249), increased liver fat (Guzman et al., Diabetes, Obesity and Metabolism, 2017, 19(11):1521–1528), and raised ambulatory blood pressure (Kazda et al., Diabetes, Obesity and Metabolism, 2017, 19(8):1071–1077); the program was discontinued. The opposite strategy, adding glucagon agonism on top of GLP-1 to burn energy while GLP-1 covers the glucose-raising, began with rodent co-agonists in 2009 (Day et al., Nature Chemical Biology, 2009, 5(10):749–757; Pocai et al., Diabetes, 2009, 58(10):2258–2266). Cotadutide reached Phase 2 (Nahra et al., Diabetes Care, 2021, 44(6):1433–1442) before its sponsor dropped it. The active programs are survodutide (le Roux et al., The Lancet Diabetes & Endocrinology, 2024, 12(3):162–173), mazdutide (Ji et al., New England Journal of Medicine, 2025, 392(22):2215–2225), and the triple agonist retatrutide (Jastreboff et al., New England Journal of Medicine, 2023, 389(6):514–526). Tirzepatide, often grouped with them, is a GIP/GLP-1 agonist and does not act at the glucagon receptor. Mazdutide is approved in China, but as of October 2026 none of the glucagon-containing agonists is FDA approved.

Common dosage forms

• Nasal powder (approved product) — a single-use intranasal device delivering 3 mg glucagon as a dry powder; absorbed through the nasal mucosa, so it works without inhalation and in an unconscious person. Stored at room temperature in a shrink-wrapped tube.
• Prefilled autoinjector and prefilled syringe (approved products) — glucagon dissolved in dimethyl sulfoxide at 0.5 mg/0.1 mL and 1 mg/0.2 mL, for subcutaneous use; a 1 mg/0.2 mL vial-and-syringe kit of the same liquid also exists. The analog dasiglucagon is a separate 0.6 mg/0.6 mL aqueous autoinjector and prefilled syringe.
• Lyophilized 1 mg vial with diluent syringe (approved product) — the classic emergency kit, now supplied by generic manufacturers as synthetic peptide; reconstituted immediately before subcutaneous, intramuscular, or intravenous injection. The same kits carry the diagnostic-aid indication.
• Intravenous diagnostic concentrate (approved product) — a 1 mg/0.2 mL ready-to-dilute vial labeled for adult radiologic examinations only, used under medical supervision.
• Research-reagent and research-vendor listings — glucagon is sold as lyophilized powder, typically in 1 mg vials, and listed in catalogs of research-peptide vendors alongside the GLP-1 class; such material is not an approved product and is not the formulation studied in any rescue trial.

Key considerations

• FDA Approved, with four live presentations and two indications. Approved drug products containing glucagon exist in nasal, liquid-autoinjector, and lyophilized-kit forms for severe hypoglycemia in people with diabetes, and in kit and intravenous-concentrate forms as a radiologic diagnostic aid. The gut-related pharmacology is the smooth-muscle relaxation behind the diagnostic use, not a digestive therapeutic role.
• It only works if the liver has glycogen. Every label carries the same warning: in prolonged fasting, adrenal insufficiency, chronic hypoglycemia, or alcohol-induced hypoglycemia there may be nothing to mobilize, and intravenous glucose is required. The pivotal trials induced hypoglycemia with insulin in otherwise fed volunteers, which is the setting where glucagon performs best. Nausea and vomiting are the most common adverse effects (26% and 15% of adults in the nasal-powder studies), and a repeat dose can trigger them again.
• Contraindications are tumor-related. Glucagon can provoke a hypertensive crisis in pheochromocytoma and rebound hypoglycemia in insulinoma, and the diagnostic-aid labels add glucagonoma; necrolytic migratory erythema has been reported with continuous infusion, including with dasiglucagon in congenital hyperinsulinism.
• The “recombinant kits” in older references no longer exist in the U.S. Lilly’s and Novo Nordisk’s recombinant emergency kits were discontinued in 2022 and 2024. The products sold today under the generic name are chemically synthesized glucagon shown to be identical to the human sequence; the distinction is manufacturing provenance, not pharmacology.
• Naming and class confusion. Glucagon is not a GLP-1 agonist and not a weight-loss drug, though both come from the same proglucagon gene and the obesity co-agonists borrow its receptor. Dasiglucagon is an analog with seven substitutions, not glucagon. Antagonizing the receptor has failed clinically on liver-fat and blood-pressure grounds, while agonizing it alongside GLP-1 is still investigational in the United States; neither outcome says anything about the approved rescue use, which rests on a different dose, route, and time scale.