Danuglipron (PF-06882961) is a small-molecule, non-peptide oral GLP-1 receptor agonist developed by Pfizer. NOTE: Danuglipron is NOT a peptide — it is a synthetic small molecule included here for comparison with peptide-based GLP-1 agonists. It is in Phase III development for type 2 diabetes and obesity. Danuglipron was initially studied as a twice-daily formulation, but Pfizer shifted focus to a once-daily modified-release formulation after the twice-daily version showed high discontinuation rates due to GI side effects.
Category: Metabolic / Oral GLP-1 Agonist (Small Molecule). Evidence rating: B (meaningful human data).
Clinical status: Phase III (once-daily modified-release formulation for T2D and obesity). Pfizer discontinued the twice-daily formulation development in 2023.
Danuglipron is a non-peptide, small-molecule agonist of the GLP-1 receptor. Unlike peptide GLP-1 agonists (semaglutide, liraglutide, tirzepatide), it is an orally bioavailable synthetic compound that binds to the GLP-1 receptor extracellular domain at a site distinct from the orthosteric peptide…
Research base: 0 registered clinical trials and 1 indexed publication reference Danuglipron.
Safety considerations: Common: nausea (up to 42%), vomiting, diarrhea — significantly higher rates than injectable GLP-1 agonists; High discontinuation rates in Phase II: up to 50% of patients in the highest dose group discontinued, primarily due to GI adverse events; GI tolerability was the primary reason Pfizer discontinued the twice-daily formulation and pivoted to modified-release.
Reviewed by the PeptideAtlas Editorial Team. Last reviewed: 2026-08-12.
Related peptides: Orforglipron.
Compare: Danuglipron vs Orforglipron.
No. Danuglipron is a synthetic small molecule (non-peptide) GLP-1 receptor agonist. It is fundamentally different from peptide GLP-1 agonists like semaglutide or liraglutide. It is included on PeptideAtlas for comparison purposes because it targets the same receptor.
The twice-daily formulation had unacceptably high GI side effect rates, with up to 50% of patients discontinuing in the highest dose group. Pfizer pivoted to a once-daily modified-release formulation designed to smooth pharmacokinetics and improve tolerability.
Oral semaglutide (Rybelsus) is a peptide that requires an absorption enhancer (SNAC) and must be taken on an empty stomach 30 minutes before food. Danuglipron is a small molecule that does not require these conditions, potentially offering more convenient dosing. However, oral semaglutide is already FDA-approved with extensive clinical data, while danuglipron is still investigational.
Phase III trials with the modified-release formulation are ongoing. If successful, regulatory submission could follow, but no specific timeline has been announced. Competition from oral semaglutide and orforglipron is intense.