Glucagon
| 證據等級: L5 | 預測適應症: 1 個 |
目錄
Glucagon: From Severe Hypoglycemia to Irritable Bowel Syndrome
One-Sentence Summary
Glucagon is an endogenous pancreatic hormone conventionally used to treat severe hypoglycemia by raising blood glucose. The TxGNN model predicts a possible link to Irritable Bowel Syndrome (IBS) with a 99.24% prediction score, but the underlying evidence — 11 clinical trials and 20 publications — is almost entirely about GLP-1 receptor agonists (ROSE-010, liraglutide, exendin‑4), a mechanistically opposite drug class, not glucagon itself. This is very likely a false-positive signal driven by name similarity between "Glucagon" and "Glucagon-Like Peptide-1 (GLP-1)."
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in this dataset (no license or indication text on file; glucagon is clinically established for severe hypoglycemia management) |
| Predicted New Indication | Irritable Bowel Syndrome |
| TxGNN Prediction Score | 99.24% (rank 8077 among model-wide candidates) |
| Evidence Level | L5 – model prediction only, no actual studies of glucagon in IBS |
| Germany Market Status | ✗ Not Marketed (未上市) |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data for glucagon is not available in this evidence pack. However, glucagon's mechanism is well established in the literature: it binds the glucagon receptor (a distinct GPCR from the GLP-1 receptor) and raises blood glucose by stimulating hepatic glycogenolysis and gluconeogenesis — the physiological opposite of insulin and of GLP-1.
This prediction does not hold up mechanistically. Every clinical trial and publication supporting the IBS association involves GLP-1 (Glucagon-Like Peptide-1) or its receptor agonists (ROSE-010, liraglutide, exendin-4, native GLP-1) — not glucagon. While glucagon and GLP-1 both derive from cleavage of the same precursor gene (proglucagon), they act on different receptors and produce opposite physiological effects (glucagon raises blood glucose and accelerates gastric emptying; GLP-1 lowers blood glucose and inhibits gastric emptying/motility). Treating them as pharmacologically equivalent is not scientifically valid.
The evidence pack's own repurposing rationale reaches the same conclusion: no mechanistic link between glucagon (DB00040) and IBS was found. This pattern is consistent with a retrieval false positive caused by shared substring/name overlap ("glucagon" appearing inside "glucagon-like peptide-1") rather than a genuine drug-repurposing signal.
Clinical Trial Evidence
⚠️ None of the trials below study glucagon itself. All involve GLP-1 or GLP-1 receptor agonists, listed here for transparency about what the underlying evidence actually supports.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01056107 | Phase 1/2 | Completed | 52 | ROSE-010 (GLP-1 receptor agonist, not glucagon) effect on GI motor function in constipation-predominant IBS |
| NCT02731664 | Phase 1 | Completed | 12 | Native GLP-1 vs. ROSE-010 inhibition of upper GI motility — no glucagon arm |
| NCT04763564 | Phase 2 | Terminated | 8 | Liraglutide (GLP-1 RA) for bowel frequency post-IPAA — mechanistically opposite to glucagon |
| NCT06408610 | N/A | Completed | 66 | Exercise effect on GLP-1 hormone and gut dysbiosis in IBS — no drug intervention |
| NCT04230655 | N/A | Unknown | 110 | Low-energy diet + intragastric balloon for obesity — no glucagon or GLP-1 drug tested |
| NCT00802971 | N/A | Completed | 12 | Fructo-oligosaccharide effect on reactive hypoglycemia — no glucagon intervention |
| NCT05249023 | N/A | Completed | 37 | Butyrate mechanism in colon health (IBS-linked) — unrelated to glucagon |
| NCT06113146 | N/A | Completed | 41 | Eating rate of ultra-processed foods on metabolic response — unrelated to glucagon |
| NCT06333717 | N/A | Completed | 33 | Whole grain rye bread effect on gut-brain axis peptides — unrelated to glucagon |
| NCT04111263 | N/A | Completed | 33 | Gut-microbiota nutritional intervention at high altitude — unrelated to glucagon |
Relevance assessment: All graded C (not directly relevant) by the underlying evidence pack — none tested glucagon as the study drug.
Literature Evidence
⚠️ All publications below concern GLP-1 physiology or GLP-1 receptor agonists, not glucagon.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35234561 | 2022 | RCT | Scand J Gastroenterol | ROSE-010 (GLP-1 RA, not glucagon) reduced pain during IBS attacks |
| 22517769 | 2012 | RCT | Am J Physiol GI Liver Physiol | Randomized double-blind study of ROSE-010 (GLP-1 analog) on GI motor function in IBS-C |
| 40134805 | 2025 | Systematic Review/Meta-analysis | Front Endocrinol | GLP-1 receptor agonists improve IBS symptoms — glucagon not evaluated |
| 30444291 | 2019 | Review | Exp Physiol | Endocrine role of GLP-1 (not glucagon) in IBS pathophysiology |
| 40697433 | 2025 | Cohort | Ann Gastroenterol | Prescription/discontinuation patterns of GLP-1 RAs in IBS patients |
| 26765585 | 2016 | Review | Expert Opin Investig Drugs | Review of investigational IBS-C drugs; glucagon not among candidates discussed |
| 31602785 | 2020 | Preclinical | Neurogastroenterol Motil | Exendin-4 (GLP-1 RA) improved GI dysfunction in rat IBS model |
| 28215540 | 2017 | Clinical correlation | Clin Res Hepatol Gastroenterol | Serum GLP-1 (not glucagon) inversely correlated with abdominal pain in IBS-C |
| 23338623 | 2013 | Preclinical | Int J Mol Med | GLP-1's role in rat models of IBS pathogenesis |
| 25427821 | 2015 | Review | Adv Exp Med Biol | Aerosolized GLP-1 (not glucagon) for diabetes and IBS |
Germany Market Information
No marketing authorization records are available for this drug in the current registry (market status: 未上市 / Not Marketed; 0 licenses on file).
Safety Considerations
Please refer to the package insert for safety information. Key warnings, contraindications, and drug-interaction data are not currently available in this dataset (flagged as Blocking data gap DG001 — TFDA label warnings/contraindications, pending retrieval).
Conclusion and Next Steps
Decision: Hold
Rationale: This candidate is very likely a false-positive prediction caused by entity confusion between "Glucagon" and "Glucagon-Like Peptide-1 (GLP-1)" — two hormones with opposing receptors and opposing physiological effects. Every piece of supporting clinical trial and literature evidence involves GLP-1 or GLP-1 receptor agonists, none involves glucagon itself, and the evidence pack is independently scored L5 ("model prediction only, no actual studies").
To proceed, the following is needed:
- Verify and correct entity disambiguation in the TxGNN knowledge graph (glucagon vs. GLP-1 node/edge separation) before this candidate is re-scored
- If a genuine preclinical rationale exists for glucagon (not GLP-1) in IBS, obtain actual glucagon-specific study data
- Resolve blocking data gap DG001 (TFDA label warnings/contraindications) and high-priority gap DG002 (MOA via DrugBank) before any further safety evaluation
- Given the drug is unmarketed in this registry, a market-access assessment would be required only if the mechanistic concern above is resolved
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.