Glucagon receptor Agonists
5 drugsAbout Glucagon receptor
The Glucagon receptor (GCGR) is a G protein-coupled receptor primarily in the liver that binds glucagon, counteracting insulin's effects. By stimulating glycogen breakdown and glucose release, GCGR raises blood sugar levels, making it crucial for glucose homeostasis.
Human genetic studies provide strong validation for GCGR as a therapeutic target, with variants linked to GCGR-related hyperglucagonemia (score 0.84). Loss-of-function variants are associated with increased disease risk, suggesting activation may be beneficial.
GCGR is targeted by 5 FDA-approved small molecule drugs, including ZEGALOGUE, BAQSIMI and GLUCAGON. These drugs, developed by companies like Viatris and Zealand Pharma, are used in metabolic conditions and other therapeutic areas.
Glucagon receptor Genetic Evidence Strong
Genetic evidence strongly supports GCGR's role in disease, with a max score of 0.84 for GCGR-related hyperglucagonemia.
Strong genetic support suggests that clinical trials targeting GCGR have a higher likelihood of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in genetic, familial or congenital disease, endocrine system disease, cancer or benign tumor pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
2 totalGWAS and other genetic studies link GCGR to 2 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for GCGR colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top Glucagon receptor Drugs
Four companies, including Viatris and Zealand Pharma, have approved drugs targeting GCGR.
The presence of established players suggests moderate barriers to entry in the GCGR-targeted drug market.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| GVOKE KIT | XERIS | 2019 | 1 |
| GVOKE HYPOPEN | XERIS | 2019 | 1 |
Glucagon receptor Drug Modality Landscape
Modalities
Routes of Administration
Glucagon receptor is druggable by small molecules, though no oral formulations are currently approved.
Exploring alternative modalities like antibodies or peptides could offer a competitive advantage in the GCGR space.
Glucagon receptor Clinical Trials 107 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Glucagon receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 43 | 33 | 5 | 5 | 87% |
| Phase 2 | 33 | 24 | 7 | 2 | 77% |
| Phase 3 | 17 | 17 | 0 | 0 | 100% |
| Phase 4 | 14 | 7 | 1 | 6 | 88% |
Top Sponsors
By Modality
Top Conditions
Glucagon receptor Drug Approval Timeline (1960 - 2019)
The first GCGR-targeting drug was approved in 1960, with the most recent in 2021.
The 62-year span indicates a mature market, but recent approvals suggest continued innovation potential.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 44 (14 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on Glucagon receptor. A trial counts if an approved drug acting on Glucagon receptor is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.