Danuglipron

also known as: PF-06882961

⚠ Not a peptide — small molecule. Pfizer's discontinued oral GLP-1 program — halted April 14, 2025 after a single case of potential drug-induced liver injury in a once-daily dose-optimization study, ending Pfizer's second oral GLP-1 failure in as many years. Included in this peptide encyclopedia because the audience frequently searches for it alongside peptide GLP-1 agonists.

A small-molecule non-peptide GLP-1 receptor agonist developed by Pfizer as a once-daily oral tablet for chronic weight management, discontinued on April 14, 2025 after a single asymptomatic participant in a dose-optimization study experienced potential drug-induced liver injury that resolved on drug withdrawal — Pfizer's second oral GLP-1 program to fail since 2023.

Mechanism of action

Binds the transmembrane region of the GLP-1 receptor as a small-molecule agonist, distinct from the orthosteric peptide-binding pocket occupied by semaglutide and other peptide GLP-1 agonists. This unusual binding mode was what allowed the oral, non-peptide format — and also what made the pharmacology subtly different from peptide GLP-1s.

Primary uses

Historical: oral chronic weight management (discontinued)
No current clinical or community use

Typical dosing

discontinued historical: once daily (final) or twice daily (earlier) (oral)

Development halted before final dose was established.

Regulatory status

Discontinued by Pfizer on April 14, 2025. Prior Phase 2b trial in adults with obesity (NCT04707313) had shown meaningful weight reductions — placebo-adjusted weight loss of approximately 8–13% at 32 weeks — but over half of participants discontinued treatment due to nausea (73%), vomiting (47%), and diarrhea (25%). Once-daily dose-optimization studies (NCT06567327, NCT06568731) met pharmacokinetic objectives but the single liver-injury case, combined with regulatory feedback, ended the program.

References

[news-release] Pfizer Inc. "Pfizer Provides Update on Oral GLP-1 Receptor Agonist Danuglipron." Press release, April 14, 2025.
[clinicaltrials] NCT04707313 — Phase 2b danuglipron in obesity. ClinicalTrials.gov.
[clinicaltrials] NCT06567327, NCT06568731 — once-daily danuglipron dose-optimization studies. ClinicalTrials.gov.

Related peptides

Semaglutide

A once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

Liraglutide

The first once-daily GLP-1 analog to be FDA-approved for both type 2 diabetes (Victoza) and chronic weight management (Saxenda).

Orforglipron

⚠ Not a peptide — small molecule. A daily oral GLP-1 agonist in Phase 3 for obesity and T2DM, distinct from Rybelsus in being a small molecule rather than an oral peptide formulation. Included in this peptide encyclopedia because the audience frequently searches for it alongside peptide GLP-1 agonists.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.