GLP-1 Agonists
4 drugsAbout GLP-1
GLP1R (glucagon-like peptide-1 receptor) regulates blood glucose and appetite, making it a key target for metabolic drug development. Activation of GLP1R is crucial for treating type 2 diabetes and obesity.
Human genetics strongly support GLP1R as a therapeutic target, with variants linked to diabetes mellitus (score 0.78), type 2 diabetes (0.76), and obesity (0.70). Activation of GLP1R is likely beneficial based on genetic evidence.
GLP1R is targeted by 17 FDA-approved drugs, including TRULICITY, RYBELSUS, and WEGOVY. Peptide-based therapies dominate (14 drugs), with biologics and small molecules also represented, spanning metabolic and other therapeutic areas.
Human Genetic Evidence Strong
GLP1R has strong genetic support with a max score of 0.78 across 24 diseases.
Strong genetic support suggests a higher probability of clinical success for GLP1R-targeting drugs.
ð¡ Why activation?
- ⢠Gain-of-function variants reduce disease risk â enhancing activity may help
- ⢠100% directional consistency across 3 traits
- ⢠Strong signal in endocrine system disease, nutritional or metabolic disease, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link GLP1R to 24 diseases.
Activating this target may be therapeutic
Activating this target may be therapeutic
ð Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for GLP1R 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 â¥0.7) â ~1.8x, Moderate (0.3-0.7) â ~1.3x, Weak â 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 â gene expression â disease, supporting the target-disease connection.
Top Drugs
Five companies have approved GLP1R-targeting drugs, with Eli Lilly and Novo Nordisk leading the market.
The concentrated market indicates high barriers to entry, requiring differentiated products for new entrants.
Drug Modality Landscape
Modalities
Routes of Administration
GLP-1 is primarily targeted by peptide modalities (88% of approved drugs).
The dominance of peptides suggests an opportunity for novel small molecule or biologic GLP1R modulators.
ð Modality Evolution
Peptides pioneered GLP-1 targeting (2010), with other biologics entering more recently (2016).
Clinical Trials 1,595 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 350 | 296 | 17 | 36 | 95% |
| Phase 2 | 315 | 171 | 26 | 115 | 87% |
| Phase 3 | 504 | 395 | 24 | 85 | 94% |
| Phase 4 | 426 | 274 | 47 | 99 | 85% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved GLP-1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting GLP-1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Drug Approval Timeline (2010 - 2024)
The first GLP1R drug was approved in 2005, with the most recent approval in 2024.
The continued approvals suggest sustained interest and potential for further innovation in GLP1R-targeted therapies.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- ⢠4 companies competing
- ⢠Market share by company
Full Drug Portfolio
- ⢠All 4 approved drugs
- ⢠Approval dates & indications
Genetic Validation
- ⢠Full genetic evidence table
- ⢠Effect sizes & directions
Approval Timeline
- ⢠Full 4-drug timeline
- ⢠First-of-modality markers
Clinical Trials Analysis
- ⢠Success rates by condition
Full summary ⢠All drugs ⢠Genetic evidence ⢠Trials ⢠Timeline