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Native glucagon must be reconstituted minutes before use because it aggregates in water; dasiglucagon's seven substitutions keep it in solution in a ready-to-use autoinjector.
Also known as: ZP4207 · ZP-GA-1 · Zegalogue
Part of the Metabolic & GLP-1 peptides cluster
Overview
Dasiglucagon (Zegalogue) is a 29-amino-acid glucagon analogue with seven amino-acid substitutions, including Aib at position 16, that make it chemically stable in aqueous solution. It activates the glucagon receptor to raise blood glucose and was approved by the US FDA in March 2021 for severe hypoglycaemia in people with diabetes aged 6 years and older, supplied as a ready-to-use autoinjector or prefilled syringe.
Source & context
Biological / chemical source: Synthetic engineered peptide (Zealand Pharma)
Primary research or clinical context: Approved (US FDA, March 2021) for severe hypoglycaemia in people with diabetes aged 6 and over; also studied in congenital hyperinsulinism and closed-loop insulin systems
What dasiglucagon is
Dasiglucagon is a synthetic analogue of human glucagon, the 29-residue pancreatic hormone that raises blood glucose. Its purpose is narrow and practical: to deliver glucagon's rescue effect from a device that needs no mixing. Native glucagon is unstable in water — it fibrillates within hours — so traditional emergency kits ship a powder and a diluent that must be reconstituted while someone is unconscious. Dasiglucagon's engineered sequence stays in solution, allowing a single-dose autoinjector or prefilled syringe. In March 2021 it received its first approval, in the United States, for severe hypoglycaemia in paediatric and adult patients with diabetes aged 6 years and above (Blair, Drugs 2021).
Sequence and the seven substitutions
The backbone listed in PubChem reads His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Aib-Ala-Arg-Ala-Glu-Glu-Phe-Val-Lys-Trp-Leu-Glu-Ser-Thr: 29 residues like glucagon, with substitutions concentrated in the C-terminal half and a non-canonical α-aminoisobutyric acid (Aib) at position 16. The design goal was physical stability — preventing the amyloid-like aggregation that native glucagon undergoes at neutral pH — while keeping receptor potency. The one-letter display above marks the Aib as X. Molecular formula and mass are given in the structure block below from the PubChem record.
How it works
Dasiglucagon activates the glucagon receptor on hepatocytes, triggering glycogen breakdown and glucose release into the blood — the same mechanism as native glucagon. The pharmacology that matters clinically is speed. In pharmacodynamic studies, a full 0.6 mg dose raised blood glucose by at least 20 mg/dL within about 9–10 minutes of insulin-induced severe hypoglycaemia in people with type 1 diabetes, and pharmacokinetic work showed higher absorption and a longer plasma elimination half-life than reconstituted glucagon (Li et al., Expert Opinion on Pharmacotherapy 2020).
Clinical evidence
Three phase 3 trials — one in children aged 6–17 and two in adults — compared dasiglucagon with placebo and with reconstituted glucagon. In all three, the median time to plasma glucose recovery was 10 minutes with dasiglucagon versus 30–40 minutes with placebo, and comparable to reconstituted glucagon; the most common adverse events were nausea, vomiting and headache, with no serious safety events (Goodhart, Annals of Pharmacotherapy 2023). Dasiglucagon has also been studied in congenital hyperinsulinism, where continuous infusion is being evaluated as an alternative to diazoxide, and as the glucagon component of bihormonal closed-loop insulin systems.
| Trial population | Dasiglucagon | Placebo |
|---|---|---|
| Adults, trial 1 | 10 | 40 |
| Adults, trial 2 | 10 | 30 |
| Children 6–17 | 10 | 35 |
Why stability matters for a rescue drug
Severe hypoglycaemia is an emergency treated by a bystander, often a family member. Every step in reconstitution — attaching a needle, injecting diluent, swirling, drawing up — is a step that can be fumbled under stress. A ready-to-use autoinjector removes them. Dasiglucagon is described in the literature as the first glucagon analogue stable in aqueous solution, making it one of only three glucagon treatments at the time of its review that did not require reconstitution (Goodhart 2023). That formulation advantage, rather than any difference in receptor pharmacology, is the reason the molecule exists.
Relation to other peptides on this site
Dasiglucagon is the therapeutic mirror image of the metabolic cluster's headline peptides. Semaglutide, tirzepatide and retatrutide lower glucose and weight; retatrutide, survodutide and mazdutide even include glucagon receptor activity as a component tuned to be weaker than their incretin effects. Dasiglucagon is pure glucagon receptor agonism, used acutely to reverse hypoglycaemia caused by insulin. The glucagon profile covers the hormone itself, and the glucagon-versus-GLP-1 guide explains why one receptor can be a weight-loss target and an emergency rescue at the same time.
Status as of September 2026
Dasiglucagon is an approved prescription medicine in the United States (Zegalogue) for severe hypoglycaemia; approvals and indications elsewhere should be checked with the relevant regulator. ClinicalTrials.gov lists completed phase 3 work in children with congenital hyperinsulinism and a Japanese comparison with glucagon. It is a supervised emergency medicine, and nothing on this page is guidance on its use.
Sequence
One-letter sequence commonly cited for Dasiglucagon (educational; isoforms and modifications may differ):
HSQGTFTSDYSKYLDXARAEEFVKWLEST
X = Aib (α-aminoisobutyric acid) at position 16. X marks a non-canonical residue — see the structure block below. (Plotted as alanine on the wheel.)
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Human glucagon (29 residues) with seven substitutions, one of them Aib16, selected for solubility and physical stability in aqueous formulation
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- PubChem molecular record · 2026-10-01
- Molecular formula
- C152H222N38O50
- Average reference mass
- ≈ 3,381.6
- Receptors
- Glucagon receptor (GCGR), the same class B G-protein-coupled receptor activated by native glucagon
- Backbone
- Human glucagon (29 residues) with seven substitutions, one of them Aib16, selected for solubility and physical stability in aqueous formulation
- Status
- Approved: US FDA, March 2021 (severe hypoglycaemia, age ≥ 6). Supplied as autoinjector or prefilled syringe
- PubChem CID: 126961379
- CAS RN: 1544300-84-6
- UNII: AD4J2O47FQ
Chemistry values: curated profile, PubChem · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 21 registered studies with “Dasiglucagon” as an intervention (snapshot 2026-09-07). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT03941236 | Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon in Children With Congenital Hyper | Phase 3 | completed | 2026-08-03 |
| NCT06588504 | Research Study in Japan to Compare Dasiglucagon With Glucagon in Treating Very Low Levels of Blood Sugar in As | Phase 1 | completed | 2025-12-05 |
| NCT05378672 | A Study to Inv. Safety, Efficacy & PD of Dasiglucagon as Hypoglycemia Rescue Therapy in Children <6 Years With | Phase 3 | completed | 2025-07-20 |
| NCT04172441 | Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyperinsulinism | Phase 3 | completed | 2025-03-14 |
| NCT05454709 | A Stable Glucagon Analog Administered by a Bihormonal Closed Loop System | Phase 2 | withdrawn | 2024-01-03 |
| NCT03777176 | A Two-Period Open-label Trial Evaluating Efficacy and Safety of Dasiglucagon in Children With Congenital Hyper | Phase 3 | completed | 2023-12-13 |
Dasiglucagon — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Human glucagon (29 residues) with seven substitutions, one of them Aib16, selected for solubility and physical stability in aqueous formulationAverage reference mass: 3,381.6 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to PubChem CID 126961379.
- TrialsClinicalTrials.gov snapshot added: 21 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Dasiglucagon
What is Dasiglucagon?+
Dasiglucagon (Zegalogue) is a 29-amino-acid glucagon analogue with seven amino-acid substitutions, including Aib at position 16, that make it chemically stable in aqueous solution. It activates the glucagon receptor to raise blood glucose and was approved by the US FDA in March 2021 for severe hypoglycaemia in people with diabetes aged 6 years and older, supplied as a ready-to-use autoinjector or prefilled syringe.
What Canadian product status is recorded for Dasiglucagon?+
Canadian product status for Dasiglucagon has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Dasiglucagon?+
Dasiglucagon is commonly described as approximately 29 amino acids (Glucagon analogue).
What is dasiglucagon?+
A 29-amino-acid glucagon analogue engineered to be stable in water, sold as the ready-to-use rescue injection Zegalogue for severe hypoglycaemia in people with diabetes. FDA-approved in March 2021.
How is dasiglucagon different from glucagon?+
Same receptor and same effect, but seven amino-acid substitutions (including Aib at position 16) keep it soluble and stable, so it needs no reconstitution before injection.
How fast does dasiglucagon work?+
In three phase 3 trials the median time to plasma glucose recovery was 10 minutes, versus 30–40 minutes with placebo and comparable to reconstituted glucagon.
What are the side effects of dasiglucagon?+
Nausea, vomiting and headache were the most common in trials; no serious safety events were reported.
Is dasiglucagon approved outside the United States?+
This profile documents the March 2021 US approval. Check the relevant regulator for other markets.
Related peptides
References & further reading
- 1.Blair HA (2021). Dasiglucagon: First Approval. Drugs
- 2.Goodhart AL (2023). Dasiglucagon: A Novel Ready-to-Use Treatment for Severe Hypoglycemia. Annals of Pharmacotherapy
- 3.Li S et al. (2020). Evaluating dasiglucagon as a treatment option for hypoglycemia in diabetes. Expert Opinion on Pharmacotherapy
- 4.Xu B et al. (2021). Dasiglucagon: an effective medicine for severe hypoglycemia. European Journal of Clinical Pharmacology
- 5.PubChem — Dasiglucagon (CID 126961379)