PPARgamma Inhibitors
5 drugsAbout PPARgamma
PPARγ (Peroxisome Proliferator-Activated Receptor gamma) is a nuclear receptor regulating gene expression related to lipid metabolism and glucose homeostasis.
Human genetics strongly support PPARγ as a therapeutic target, with variants linked to PPARG-related familial partial lipodystrophy (score 0.85) and type 2 diabetes (score 0.83). Activation is likely beneficial based on genetic evidence.
PPARγ is targeted by 5 FDA-approved small molecule drugs, including ACTOS, LIVDELZI and PIOGLITAZONE HYDROCHLORIDE. Three drugs target metabolic conditions, while two address other therapeutic areas.
PPARgamma Genetic Evidence Strong
Strong genetic evidence supports PPARγ's role in diseases like lipodystrophy and type 2 diabetes.
The high genetic scores suggest that clinical trials targeting these genetically validated indications have an increased likelihood of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 50% directional consistency across 2 traits
- • Strong signal in genetic, familial or congenital disease, nutritional or metabolic disease, integumentary system disease pathways
Cross-Disease Effects
Trade-off: HighDirection of Effect
50% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link PPARG to 36 diseases.
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for PPARG 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 PPARgamma Drugs
Four companies have approved drugs targeting PPARγ, including CHARTWELL RX, TORRENT PHARMS LTD, Gilead Sciences, and Takeda.
The presence of multiple players indicates a moderately competitive market, but also potential partnership opportunities.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| PIOGLITAZONE HYDROCHLORIDE | CHARTWELL RX | 2012 | 1 |
| DUETACT | Takeda | 2006 | 1 |
PPARgamma Drug Modality Landscape
Modalities
Routes of Administration
PPARgamma is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage in this space.
PPARgamma Clinical Trials 1,153 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on PPARgamma. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 288 | 230 | 25 | 33 | 90% |
| Phase 2 | 322 | 178 | 84 | 60 | 68% |
| Phase 3 | 260 | 197 | 28 | 34 | 88% |
| Phase 4 | 283 | 207 | 40 | 36 | 84% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved PPARgamma drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting PPARgamma. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
PPARgamma Drug Approval Timeline (1999 - 2024)
The first PPARγ-targeting drug was approved in 1999, with the most recent approval in 2024.
The continued approvals suggest ongoing interest and potential for further innovation in this target area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 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: 512 (110 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 PPARgamma. A trial counts if an approved drug acting on PPARgamma 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.