Glucagon

Glucagon: GlucaGen HypoKit, Glucagon Emergency Kit (Lilly), Gvoke (liquid, pre-filled), Baqsimi (nasal powder), Ogluo (EU name for Gvoke). Dasiglucagon: Zegalogue, ZP4207

Metabolic & weight
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Note on this profile. Glucagon and dasiglucagon are approved prescription medicines, chiefly emergency treatments for severe low blood sugar in people on insulin. This page explains the published science. Community/self-directed use outside diabetes management is essentially none documented; the "mini-dose glucagon" practice described below belongs to type 1 diabetes self-care, not to enhancement protocols.

1What it is

Glucagon is insulin's opposite. It is made by the alpha cells of the pancreatic islets and released when blood sugar falls, telling the liver to break down glycogen and release glucose. It was discovered in 1923, within two years of insulin, and crystallised in the 1950s. The drug is a copy of the human hormone (older products were extracted from pig and cow pancreas). Its medical uses are: rescuing a person with severe hypoglycaemia who cannot swallow (the main one), relaxing the gut as a diagnostic aid during X-ray and endoscopy, and a handful of off-label emergency uses such as beta-blocker overdose.

Glucagon's practical problem has always been that it is insoluble and unstable in water: it fibrillates (clumps into fibres) within hours, so for decades it had to be sold as a powder with a separate syringe of to mix in an emergency — a procedure caregivers often got wrong under stress. Three solutions arrived in 2019–2021: a ready-to-use nasal powder (Baqsimi), a non-aqueous liquid glucagon (Gvoke/Ogluo), and dasiglucagon (Zegalogue), an analogue developed by Zealand Pharma in which seven amino acids are swapped so the molecule stays dissolved and stable in a standard water-based autoinjector. Dasiglucagon is also the glucagon component in dual-hormone "bionic pancreas" research pumps and has been tested as a continuous infusion for congenital hyperinsulinism (a rare genetic cause of dangerous low sugar in infants).


2How it's thought to work

The glucagon receptor is a G-protein-coupled receptor (same family as GLP-1 and GIP receptors) concentrated in the liver. Activation raises cAMP, activates glycogen phosphorylase and switches on gluconeogenesis; blood glucose rises by ~2–4 mmol/L within 10–20 minutes.
It only works if the liver has glycogen. After prolonged fasting, heavy alcohol, or in adrenal insufficiency and chronic liver disease, the response can be weak — which is why intravenous dextrose remains first-line when a clinician is present.
Glucagon relaxes smooth muscle of the stomach and intestine (the basis for the diagnostic use), stimulates insulin release in healthy people (the basis of the glucagon stimulation test), raises heart rate and contractility via cardiac receptors independent of beta-adrenergic signalling (beta-blocker overdose), and causes nausea by acting on the brainstem.
Dasiglucagon is pharmacologically indistinguishable from glucagon at the receptor; the differences are physical stability and a slightly longer .
Glucagon from the pancreatic alpha cell acting on the liver. Stored glycogen is broken down and new glucose is made, and the sugar leaves into the blood — the counterweight to insulin, and the emergency treatment for severe hypoglycaemia.Schematic — not to scale

3What the research shows

Rescue of severe hypoglycaemia

Injected glucagon 1 mg restores consciousness and raises glucose in the large majority of insulin-induced hypoglycaemia episodes within 10–15 minutes; this is decades-old standard of care supported by controlled crossover studies rather than modern placebo . Nasal glucagon 3 mg achieved treatment success (glucose ≥70 mg/dL or rise ≥20 mg/dL within 30 min) in 98.7% of induced hypoglycaemia episodes vs 100% for 1 mg IM in a crossover trial of 75 adults with type 1 diabetes, with similar timing (Rickels 2016, Diabetes Care). Real-world studies showed caregivers administer nasal glucagon correctly far more often than the mixing kit. [1]

Dasiglucagon autoinjector

In a phase 3 trial (n=170 adults with type 1 diabetes, insulin-induced hypoglycaemia), median time to plasma glucose recovery was 10 minutes with dasiglucagon 0.6 mg vs 40 minutes with placebo and 12 minutes with glucagon; 99% recovered within 15 minutes (Pieber 2021, Diabetes Care). A paediatric trial (ages 6–17) gave the same result (Battelino 2021, Pediatr Diabetes). [2][3]

Mini-dose glucagon for impending hypoglycaemia

Small doses (10 µg per year of age in children) raised glucose by ~3–5 mmol/L and avoided emergency visits in children with gastroenteritis who could not keep food down (Haymond & Schreiner 2001, Diabetes Care). A crossover study in adults showed 150 µg before exercise prevented exercise-induced hypoglycaemia as well as carbohydrate, without the weight gain (Rickels 2018, Diabetes Care). Off-label. [4][5]
Graded A/B

Congenital hyperinsulinism

Phase 3 trials of continuous subcutaneous dasiglucagon infusion in infants and children reduced the need for intravenous glucose and the number of hypoglycaemic events (Banerjee / De León 2024 and related reports). Two FDA complete response letters in 2023–2024 cited manufacturing-site inspection timing, not efficacy or safety †.
Graded A (device trials)

Bihormonal closed-loop insulin pumps

Dual-hormone systems delivering insulin and dasiglucagon or glucagon reduce hypoglycaemia compared with insulin-only closed loop in short trials (El-Khatib 2017, Lancet, with glucagon); no bihormonal system is yet commercially approved. [6]
Graded C/B

Beta-blocker and calcium-channel blocker overdose, oesophageal food impaction, anaphylaxis on beta-blockers

Case series and animal data; glucagon's use for food bolus impaction did not beat placebo in RCTs. Off-label and hospital-only.

4Reported side effects and interactions

Literature-reported

Literature. nausea (≈30–60% after a full 1 mg rescue dose) and vomiting are the most common; headache, injection-site pain, transient tachycardia and raised blood pressure. Nasal glucagon adds watery eyes, nasal congestion, itching and sneezing. Dasiglucagon's profile matched glucagon (nausea 57%, vomiting 25%, headache 11% in the phase 3 trial). Rebound hypoglycaemia can follow because glucagon also stimulates insulin and depletes glycogen — eating carbohydrate once able to swallow is part of the label instruction. Rare allergic reactions, including anaphylaxis. Generalised allergic reactions and a rare syndrome of necrolytic migratory erythema (skin rash) with continuous infusion have been reported.

Contraindications (label). pheochromocytoma (glucagon triggers catecholamine release — severe hypertension), insulinoma (glucagon stimulates insulin release and can cause rebound hypoglycaemia), glucagonoma (dasiglucagon label).

Community-reported

none documented outside diabetes self-management forums.

Theoretical. chronic glucagon exposure would be catabolic (it is the "fasting" hormone) and is not used in any enhancement context; glucagon receptor agonism is a component of experimental multi-agonist weight-loss drugs (survodutide, retatrutide), where it is paired with GLP-1 to raise energy expenditure.

Interactions. beta-blockers may blunt the heart-rate response and increase the blood-pressure rise; indomethacin may abolish the glucose response; glucagon increases the anticoagulant effect of warfarin after repeated doses; insulin counteracts it (by design); anticholinergic drugs add to the gut-relaxing effect when used diagnostically.

Markers researchers commonly monitor

MarkerWhy it's watched
Blood glucose (fingerstick or CGM)the only marker that matters acutely; check 15 min after a rescue dose and watch for rebound hypoglycaemia over the following hours.
Serum potassiumglucagon shifts potassium into cells via insulin release; relevant with repeated or infused doses.
Heart rate and blood pressuretransient rises; important if used in beta-blocker overdose or in people with cardiac disease.
Liver glycogen status (history of fasting, alcohol, liver disease)not a lab test but the main determinant of whether glucagon will work.
Glucagon stimulation test (GH and cortisol response)glucagon is itself a diagnostic reagent for growth hormone and adrenal reserve, a separate use from rescue.

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5Reconstitution and handling

glucagon kits (1 mg vial plus 1 mL syringe) are mixed immediately before use: inject the diluent, swirl until clear, draw up and inject; discard any unused portion as fibrillation begins within hours. Gvoke, Baqsimi and Zegalogue require no preparation and are designed for a bystander to use by following the printed steps. Note that research-market "glucagon" vials have no legitimate role outside these approved products. The calculator is not relevant to this compound.


6Commonly studied alongside

Insulin (profile 128), as the rescue agent for its main side effect, and in bihormonal pumps; GLP-1 receptor agonists and the dual/triple agonists in development (glucagon-receptor agonism as a component of survodutide, retatrutide, mazdutide — see Tirzepatide and Retatrutide profiles); diazoxide and octreotide (profile 124) in congenital hyperinsulinism; dextrose.

Informational cross-links. Not stack recommendations.


7Regulatory status by region

RegionStatus (checked —)
United StatesFDA-approved: glucagon emergency kits (Lilly, Novo GlucaGen), Gvoke (Sept 2019), Baqsimi (July 2019; now Amphastar), Zegalogue (March 2021, age 6+). Dasiglucagon for congenital hyperinsulinism: two complete response letters (Dec 2023, Oct 2024) †
European UnionGlucaGen HypoKit, Ogluo (liquid glucagon, 2021), Baqsimi (2019) authorised; Zegalogue status †
United KingdomMHRA-licensed GlucaGen HypoKit, Baqsimi, Ogluo; prescription-only
AustraliaTGA-registered GlucaGen; Baqsimi registered 2020 †; Zegalogue †
South AfricaGlucaGen HypoKit registered; others †
SportNot on the WADA Prohibited List

8Open questions

  • Whether ready-to-use formats improve real-world outcomes (fewer ambulance calls, less fear of hypoglycaemia) beyond the clear usability gains.
  • Final regulatory outcome for dasiglucagon in congenital hyperinsulinism and whether long-term infusion is safe.
  • The role of glucagon-receptor agonism within multi-agonist obesity drugs.

9References

  1. 1Rickels MR et al. (2016). Intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: a randomized crossover noninferiority study. Diabetes Care. PubMed · DOI
  2. 2Pieber TR et al. (2021). Dasiglucagon — a next-generation glucagon analog for rapid and effective treatment of severe hypoglycemia: results of phase 3 randomized double-blind clinical trial. Diabetes Care. PubMed · DOI
  3. 3Battelino T et al. (2021). Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: results of a phase 3, randomized controlled trial. Pediatr Diabetes. PubMed · DOI
  4. 4Haymond MW, Schreiner B (2001). Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes. Diabetes Care. PubMed · DOI
  5. 5Rickels MR et al. (2018). Mini-dose glucagon as a novel approach to prevent exercise-induced hypoglycemia in type 1 diabetes. Diabetes Care. PubMed · DOI
  6. 6El-Khatib FH et al. (2017). Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. PubMed · DOI
  7. 7Hövelmann U et al. (2018). Pharmacokinetic and pharmacodynamic characteristics of dasiglucagon, a novel soluble and stable glucagon analog. Diabetes Care. PubMed · DOI
  8. 8Zealand Pharma. Zegalogue (dasiglucagon) prescribing information; Lilly/Amphastar. Baqsimi prescribing information; Novo Nordisk. GlucaGen prescribing information (current labels). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.


10Community

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Self-reported side effects Phase 2

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11Page history

30 Oct 2026Profile published — awaiting medical review

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