Glucagon
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Glucagon: From Severe Hypoglycemia to Irritable Bowel Syndrome
One-Sentence Summary
Glucagon is a pancreatic peptide hormone, marketed in the US mainly as an emergency treatment for severe hypoglycemia. The TxGNN model predicts it may help with irritable bowel syndrome (IBS), with a very high score of 99.2%. The 11 clinical trials and 20 publications retrieved almost all concern GLP-1 receptor agonists (a related peptide class) or non-drug interventions. None tests glucagon itself in IBS.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the US license records supplied; severe hypoglycemia is inferred from the marketed products (e.g., Gvoke, Zegalogue) |
| Predicted New Indication | Irritable bowel syndrome |
| TxGNN Prediction Score | 99.24% |
| Evidence Level | L4 (mechanistic and preclinical support only, from a related drug class) |
| US Market Status | ✓ Marketed |
| Number of NDAs | 11 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for glucagon is not available in the Evidence Pack. Glucagon and GLP-1 both derive from proglucagon, and both inhibit gastrointestinal smooth muscle motility. Glucagon is already used as a short-acting GI spasmolytic during diagnostic procedures.
IBS is driven largely by abnormal gut motility and visceral pain. A drug that relaxes gut muscle could plausibly reduce spasm and pain. The stronger support comes from GLP-1 analogs. For example, ROSE-010 reduced pain during IBS attacks and slowed gastric emptying in constipation-predominant IBS (IBS-C). Animal studies also show GLP-1 receptor activation improves gut dysfunction in IBS models.
This is an inference from a related peptide class, not direct evidence for glucagon. Glucagon’s short half-life and its tendency to raise blood glucose and cause nausea would also limit chronic use in IBS.
Clinical Trial Evidence
Most trials below study GLP-1 drugs, diet, or exercise, not glucagon.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01056107 | Phase 1/2 | Completed | 52 | ROSE-010 (GLP-1 analog) on gut motor function in women with IBS-C; supports the GLP-1 pathway only |
| NCT02731664 | Phase 1 | Completed | 12 | Native GLP-1 vs ROSE-010 on stomach and small-intestine motility; shows GLP-1 inhibits gut motility, not tested in IBS patients |
| NCT04763564 | Phase 2 | Terminated | 8 | Liraglutide vs placebo in ileal pouch patients with high bowel frequency; too small to be informative |
| NCT06408610 | N/A | Completed | 66 | Two exercise programs and their effect on gut bacteria and GLP-1 levels in IBS; no drug tested |
| NCT05249023 | N/A | Completed | 37 | Butyrate’s mode of action in the human colon; loosely related through gut hormone readouts |
| NCT00802971 | N/A | Completed | 12 | Fructo-oligosaccharide supplement in reactive hypoglycemia; nutritional, not glucagon-based |
| NCT06333717 | N/A | Completed | 33 | Rye bread and the gut-brain axis in healthy people; nutrition study |
| NCT04111263 | N/A | Completed | 33 | Fiber and polyphenol blend for gut barrier integrity at simulated high altitude; nutrition study |
| NCT04230655 | N/A | Unknown | 110 | Low-energy diet with or without intragastric balloon in obesity; not relevant to IBS |
| NCT06113146 | N/A | Completed | 41 | Eating rate of ultra-processed foods and intake; not relevant |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22517769 | 2012 | RCT | Am J Physiol Gastrointest Liver Physiol | Randomized, placebo-controlled dose-response study of ROSE-010 (GLP-1 analog) on GI motor function in women with IBS-C |
| 35234561 | 2022 | RCT (cross-analysis) | Scand J Gastroenterol | ROSE-010 reduced pain during IBS attacks; exploratory analysis to find the best-responding patient subgroup |
| 40134805 | 2025 | Systematic review | Front Endocrinol | Meta-analysis on GLP-1 receptor agonists in IBS; GLP-1 and ROSE-010 inhibit gut motility in IBS patients |
| 40697433 | 2025 | Cohort | Ann Gastroenterol | Real-world prescribing and discontinuation of GLP-1 agonists in IBS patients; GI side effects are a concern |
| 30444291 | 2019 | Review | Exp Physiol | Role of GLP-1-secreting L-cells in IBS pathophysiology |
| 25427821 | 2015 | Review | Adv Exp Med Biol | Aerosolized GLP-1 as a possible treatment for diabetes and IBS |
| 28215540 | 2017 | Observational | Clin Res Hepatol Gastroenterol | Lower GLP-1 levels correlate with abdominal pain in IBS-C |
| 31602785 | 2020 | Preclinical (rat) | Neurogastroenterol Motil | GLP-1 agonist exendin-4 improved gut dysfunction in a rat IBS model |
| 23338623 | 2013 | Preclinical (rat) | Int J Mol Med | GLP-1 involvement in gut motility and visceral hypersensitivity in rat IBS models |
| 26765585 | 2016 | Review | Expert Opin Investig Drugs | Novel investigational drugs for IBS-C |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA201849 | Glucagon (Fresenius Kabi USA) | Injection, powder, lyophilized, for solution | Not specified in source data |
| NDA212097 | Gvoke HypoPen (Xeris) | Injection, solution | Not specified in source data |
| NDA212097 | Gvoke PFS (Xeris) | Injection, solution | Not specified in source data |
| NDA214231 | Zegalogue (Novo Nordisk) | Injection, solution | Not specified in source data |
| Not listed | Glucagon (Professional Complementary Health Formulas) | Liquid | Not specified in source data |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is very high, but the supporting clinical work tests GLP-1 analogs, not glucagon, so this remains a research question. Glucagon’s short half-life, hyperglycemic effect, and nausea also make chronic IBS use unlikely without a new formulation or approach.
To proceed, the following is needed:
- Package insert warnings and contraindications (needed for safety screening)
- Mechanism-of-action data for glucagon, and a comparison of glucagon and GLP-1 effects on gut motility and visceral pain
- Direct evidence for glucagon in IBS, such as a small proof-of-concept study of short-term use for acute pain or spasm attacks
- An assessment of route and formulation feasibility, since current products are injectables for emergency use
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.