Glucagon — GlucaGen/Baqsimi/Gvoke, pancreatic counter-regulatory hormone
29-aa pancreatic alpha-cell hormone; FDA-approved since 1960 for hypoglycemia rescue and GI diagnostic use; GCGR agonist driving hepatic glycogenolysis; modernized formulations include intranasal Baqsimi (2019)
- Class
- Pancreatic counter-regulatory peptide hormone
- Status
- FDA-approved prescription drug (US); approved by EMA, MHRA, Health Canada, and TGA in equivalent jurisdictions
- Best-supported effect
- Emergency reversal of severe hypoglycemia in insulin-treated diabetic patients with intact hepatic glycogen
- Main caveat
- Effective only when hepatic glycogen is available; not validated as a standalone weight-loss agent — the obesity-related effects often attributed to "glucagon" come from dual/triple receptor agonists, which are separate molecules
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
Snapshot
Class: Pancreatic counter-regulatory peptide hormone
Evidence tier: Approved drug
Status: FDA-approved prescription drug (US); approved by EMA, MHRA, Health Canada, and TGA in equivalent jurisdictions
Best-supported effect: Emergency reversal of severe hypoglycemia in insulin-treated diabetic patients with intact hepatic glycogen
Main caveat: Effective only when hepatic glycogen is available; not validated as a standalone weight-loss agent — the obesity-related effects often attributed to "glucagon" come from dual/triple receptor agonists, which are separate molecules
What this is
Glucagon is a 29-amino-acid peptide hormone secreted by pancreatic alpha cells. It is the primary counter-regulatory hormone to insulin: when blood glucose drops, glucagon signals the liver to release stored glucose by mobilizing glycogen and producing new glucose. Synthetic glucagon has been an FDA-approved emergency rescue medication since 1960, with reformulated 2019 products (Baqsimi intranasal powder; Gvoke pre-mixed liquid auto-injector and pre-filled syringe) that removed the reconstitution step required by older lyophilized injection kits. Glucagon is also FDA-approved as a diagnostic aid for smooth-muscle relaxation during gastrointestinal imaging procedures. The glucagon receptor is additionally a component target of investigational and regional dual/triple agonist obesity drugs (mazdutide, survodutide, retatrutide), but those are separate molecules with their own evidence and regulatory tracks.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | Approved | Decades of clinical use as emergency rescue for severe hypoglycemia; multiple FDA-approved formulations including modernized 2019 products |
| Animal | Strong | Glucagon biology is fundamental to metabolic physiology; comprehensive preclinical characterization. Detailed animal study data not individually extracted |
| In vitro | Strong | Glucagon receptor signaling characterized in hepatocyte and adipose-tissue assay systems |
| Mechanism | Strong | Class B GPCR (GCGR) → adenylyl cyclase → cAMP → PKA → glycogen phosphorylase activation and glycogen synthase inhibition; one of the best-characterized hormone pathways in metabolism |
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Reverses severe hypoglycemia in insulin-treated diabetic patients with intact hepatic glycogen | Supported | Human, FDA label | High |
| Provides smooth-muscle relaxation as a diagnostic aid for GI imaging | Supported | Human, FDA label | High |
| Effective in patients with depleted hepatic glycogen (prolonged starvation, severe liver disease, chronic alcohol use, adrenal insufficiency) | Contradicted / not effective | Human, FDA label | High — IV dextrose is the labeled alternative |
| Native single-dose glucagon causes sustained weight loss | Contradicted / not established | Human | High — weight-loss effects attributed to "glucagon" come from separate dual/triple receptor agonist molecules |
| Intranasal Baqsimi is less effective than injectable formulations in real-world emergencies | Contradicted | Human | Medium — head-to-head usability studies favored intranasal in lay-caregiver scenarios; clinical equivalence in real-world emergencies is incompletely characterized |
| Routine glucagon prescribing reduces severe hypoglycemia hospitalization at the population level | Not established | Human | Low — population-level outcome data not well quantified per source |
Exposure studied
This section reports exposure used in labels and human studies. It is not a personalized protocol.
| Context | Population | Exposure studied | Duration | Endpoint | Evidence strength |
|---|---|---|---|---|---|
| FDA label (GlucaGen / Lilly Glucagon Emergency Kit) | Adults and pediatric patients ≥25 kg with severe hypoglycemia | 1 mg subcutaneous or intramuscular injection (single dose) | Single acute administration; if no response within 15 minutes, label directs seeking emergency medical care | Plasma glucose elevation; recovery of consciousness | Approved label |
| FDA label (GlucaGen / Lilly Glucagon Emergency Kit, pediatric) | Pediatric patients <25 kg or younger than 6 years | 0.5 mg subcutaneous or intramuscular injection (single dose) | Single acute administration | Plasma glucose elevation | Approved label |
| FDA label (Baqsimi, intranasal) | Adults and pediatric patients ≥4 years | 3 mg intranasal powder, single fixed dose | Single acute administration | Plasma glucose elevation; recovery of consciousness | Approved label (2019) |
| FDA label (Gvoke HypoPen / Gvoke PFS) | Adults and pediatric patients (weight band) | 0.5–1 mg pre-mixed liquid by auto-injector or pre-filled syringe | Single acute administration | Plasma glucose elevation | Approved label (2019) |
| FDA label, diagnostic GI imaging | Patients undergoing GI imaging | 0.25–2 mg IV depending on procedure and target relaxation | Single dose during imaging window | Smooth-muscle relaxation | Approved label |
Onset, peak, and offset described in available literature: plasma glucose typically begins rising within 5–10 minutes of injection; peak elevation occurs at approximately 15–30 minutes; plasma half-life is approximately 8–18 minutes; glycemic effect resolves within 60–90 minutes. Diagnostic GI relaxation typically occurs within 1–3 minutes of IV administration.
Safety signals
| Signal | Evidence context | Notes |
|---|---|---|
| Nausea and vomiting | Label / human use | Commonly reported; source notes patients should be turned on their side after rescue because vomiting is common as blood sugar rises |
| Headache | Label / human use | Commonly reported |
| Transient hyperglycemia | Label / human use | Expected pharmacology |
| Rebound hypoglycemia | Label / human use | Common within 1–2 hours of rescue if oral carbohydrate is not consumed; glucagon does not address the underlying cause of hypoglycemia |
| Anaphylactic / hypersensitivity reactions | Label | Reported but rare |
| Ineffectiveness in glycogen-depleted states | Label | Prolonged starvation, severe hepatic disease, chronic alcohol use, adrenal insufficiency — IV dextrose is the labeled appropriate intervention |
Label contraindications and cautions:
- Pheochromocytoma — glucagon can stimulate catecholamine release from the tumor and precipitate hypertensive crisis.
- Insulinoma — glucagon may initially raise blood glucose but can trigger a paradoxical insulin surge from the tumor, worsening hypoglycemia.
- Glucagonoma — additional glucagon administration in a patient already producing pathological excess is contraindicated.
- Known hypersensitivity to glucagon or formulation excipients.
- Diagnostic-use cautions: conditions where smooth-muscle relaxation is undesirable (severe ileus, mechanical obstruction needing surgical evaluation).
Interaction signals from label/source:
- Warfarin: glucagon can potentiate the anticoagulant effect; relevant primarily in repeated diagnostic glucagon administration rather than single-dose rescue.
- Beta-blockers: can blunt the catecholamine response to hypoglycemia and theoretically prolong recovery time after glucagon rescue; rarely changes acute clinical management per source.
- Indomethacin: can interfere with glucagon's hyperglycemic effect by blocking hepatic glucose output, potentially reducing rescue efficacy.
- Insulin and oral hypoglycemics: glucagon's transient hyperglycemic effect is the intended pharmacology in the rescue context.
- Dual/triple agonist molecules incorporating glucagon receptor agonism (mazdutide, survodutide, retatrutide) have their own distinct interaction profiles characterized in their respective trial programs.
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Approved prescription drug | Multiple branded products: GlucaGen (Novo Nordisk, reconstituted injection); Lilly Glucagon Emergency Kit (reconstituted injection); Baqsimi (Lilly, intranasal powder, 2019); Gvoke HypoPen / Gvoke PFS (Xeris, pre-mixed liquid, 2019). Generic injectable glucagon also exists. All formulations prescription-only |
| EU (EMA) | Approved | Native glucagon products including GlucaGen approved per source |
| UK (MHRA) | Approved | Per source |
| Canada (Health Canada) | Approved | Per source |
| Australia (TGA) | Approved | Per source |
| WADA | per available sources as prohibited | Source describes native glucagon as a peptide hormone falling under WADA S2 (peptide hormones, growth factors, related substances and mimetics), prohibited at all times. Therapeutic Use Exemptions cover diabetic athletes who require glucagon as rescue medication. Current list status not independently refreshed in this card |
The dual and triple receptor agonists incorporating glucagon receptor agonism (mazdutide, survodutide, retatrutide) are separate molecules subject to their own regulatory status and are not covered by this card's regulatory rows.
Clinical trials
Individual trial rows are not fully extracted in this card. Human evidence discussed in the Evidence map and Claim check sections above. See References for source PMIDs.
Mechanism
Glucagon binds to the glucagon receptor (GCGR), a Class B G-protein-coupled receptor expressed on hepatocytes. Receptor activation engages adenylyl cyclase and elevates intracellular cAMP, activating PKA. PKA phosphorylates glycogen phosphorylase (stimulating glycogenolysis) and inhibits glycogen synthase, mobilizing hepatic glycogen into circulating glucose. PKA signaling also activates gluconeogenic enzymes (PEPCK, G6Pase) for de novo glucose production. In adipose tissue, glucagon promotes lipolysis. The glucagon receptor is also a target in newer obesity drug candidates (e.g., retatrutide), where chronic controlled glucagon agonism is reported to increase energy expenditure — but those are separate molecules with their own evidence packages.
The rescue mechanism depends on intact hepatic glycogen stores. In states of glycogen depletion — prolonged starvation, severe hepatic disease, chronic alcohol use, adrenal insufficiency — the rescue mechanism has nothing to mobilize and glucagon will be ineffective. IV dextrose is the labeled appropriate intervention in those settings.
Chemistry
| Field | Value |
|---|---|
| Class | Peptide hormone |
| Length | 29 amino acids |
| Origin | Endogenous; synthetic recombinant or pre-mixed liquid forms used clinically |
| Topology | Linear |
| Sequence | not individually extracted's available literature |
| Sequence confidence | Sequence not present in available literature |
Open questions
- Real-world equivalence of routes: Whether intranasal Baqsimi and injectable formulations (GlucaGen, Gvoke) are clinically equivalent in real-world emergencies — where caregiver familiarity and ease of administration dominate outcomes — is incompletely characterized per available sources.
- Glucagon use under GLP-1 receptor agonist therapy: Optimal use of rescue glucagon in patients on GLP-1 receptor agonists, who may have altered counter-regulatory responses, is described as an emerging area of study.
- Long-term safety of chronic glucagon receptor agonism: Long-term controlled glucagon receptor agonism via dual/triple agonists (mazdutide, survodutide, retatrutide) has different safety considerations from single-dose rescue use, and these are being characterized through dedicated Phase 3 programs — separate from this card.
- Pediatric mini-dose glucagon: Subcutaneous low-dose glucagon for milder pediatric hypoglycemia is described as off-label use without dedicated approved formulations.
- Population-level rescue impact: Whether routine glucagon prescribing for at-risk patients meaningfully reduces severe hypoglycemia hospitalization rates at the population level is not well quantified per available sources.
- Access and uptake: Cost and access barriers, and the fraction of at-risk patients who actually carry a current emergency device, remain noted gaps despite improved formulation usability.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8560175895690918 | openfold3-mlx |
| ranking score | 0.9060197472572327 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.697 | global PDE — lower = better |
| disorder | 0.144 | fraction disordered |
| chain pair ipTM (A, B) | 0.856 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 443s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-23 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep04430,
sequence = {HSQGTFTSDYSKYLDSRRAQDFVQWLMNT},
target = {gcgr},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}