Danuglipron: Mechanism, Research & UK Safety Profile
Also known as: PF-06882961
Investigational oral non-peptide small-molecule GLP-1 receptor agonist developed by Pfizer. Programme has undergone significant changes during 2023-2025 including discontinuation of twice-daily formulation. Listed here as a non-peptide comparator for context.
Molecular formula
C31H30FN5O4
Molecular weight
555.6 g/mol (small molecule, free base)
Half-life
Pharmacokinetic profile redesigned through the programme's lifetime.
Category
Oral non-peptide GLP-1 receptor agonist (comparator)
Overview
Danuglipron (PF-06882961) is an investigational small-molecule GLP-1 receptor agonist developed by Pfizer. The development programme has experienced significant changes during 2023-2025: the twice-daily formulation was discontinued in late 2023 due to tolerability findings, and a once-daily modified-release formulation has been pursued. Programme status has evolved further during 2024-2025. Danuglipron is investigational.
Discovery & Research History
Danuglipron emerged from Pfizer's small-molecule GLP-1 programme as a counterpart to peptide GLP-1 RAs. Early phase 2 data demonstrated weight and HbA1c effects. The original BID formulation was discontinued after a phase 2b readout in late 2023 indicated higher-than-anticipated discontinuation rates. The once-daily modified-release programme has subsequently had its own status changes.
Mechanism of Action
Small-molecule allosteric activation of the GLP-1 receptor. Like orforglipron, danuglipron is orally absorbable without a specialised absorption enhancer. Pharmacokinetic engineering for once-daily dosing has been a focal point of programme development.
Researched Effects
- Body-weight reduction in earlier phase 2 obesity data.
- HbA1c reduction in phase 2 T2D data.
Theoretical Research Protocols
- Dosage range
- Trial-arm doses are research records.
- Frequency
- Once-daily modified-release in the more recent formulation.
- Duration
- Phase 2 readouts span 16-32 weeks; phase 3 programme status has evolved.
- Administration routes
- Oral (clinical trial setting)
Safety Profile
Common side effects (research)
- Gastrointestinal events consistent with the GLP-1 class.
- Liver-enzyme elevations have been reported and contributed to programme decisions.
Rare risks
- Hepatic safety has been a focus of programme-status decisions.
Contraindications
- Investigational compound; eligibility per current trial protocol.
UK Regulatory Status
United Kingdom (MHRA): Investigational. Not MHRA-licensed.
European Union (EMA): Investigational.
Notes: Programme has had material changes during 2023-2025. Pfizer's pipeline disclosures and ClinicalTrials.gov are the current authoritative references.
Related research resources
Key Research Studies
Danuglipron (PF-06882961) phase 2b obesity trial — Pfizer (ClinicalTrials.gov NCT04707313)
Phase 2b trial of twice-daily danuglipron in adults with obesity. Earlier phase 2 data reported body-weight and HbA1c effects; the twice-daily formulation was discontinued after the phase 2b readout, and programme status has continued to evolve.
Read sourceFrequently Asked Questions
What is the current status of danuglipron?
Danuglipron's development programme has had material changes during 2023-2025, including discontinuation of the twice-daily formulation in late 2023. Subsequent programme changes have followed. The current ClinicalTrials.gov / Pfizer pipeline is the authoritative reference.
Is danuglipron licensed in the UK?
No. Danuglipron is investigational and is not licensed by the MHRA for any human therapeutic indication.
Related trials
No published trials yet linked to this page. Source verification required.