An oral non-peptide GLP-1 agonist from Pfizer — twice-daily pill form in clinical development.
Danuglipron is an investigational oral, non-peptide GLP-1 receptor agonist developed by Pfizer. Like Eli Lilly's orforglipron, it represents the next generation of GLP-1 therapy: a small molecule that can be taken as a pill without the absorption limitations of peptide-based oral formulations.
Danuglipron differs from orforglipron in its dosing schedule — current formulations require twice-daily administration, though Pfizer is developing a once-daily modified-release version. It activates the same GLP-1 receptors as injectable semaglutide but as a chemically distinct small molecule with different pharmacokinetic properties.
As of 2025, Pfizer pivoted from the twice-daily formulation (which showed concerning liver enzyme elevations) to focus on the once-daily modified-release version, which showed improved tolerability in early studies.
Phase 2b results showed dose-dependent weight loss of up to 8-10% at 26 weeks with the twice-daily formulation. However, hepatic transaminase elevations in some patients led Pfizer to discontinue the twice-daily program and refocus on the once-daily formulation.
The once-daily modified-release formulation showed lower rates of liver-related adverse events in preliminary data. The competitive landscape includes orforglipron (Lilly), which is further ahead in clinical development. Results from the once-daily program are anticipated.
📚 Key Reference: PMID: 37740293 (danuglipron Phase 2b)
The twice-daily formulation showed liver enzyme elevations (ALT/AST) that led to program restructuring. GI side effects (nausea, vomiting, diarrhea) are similar to injectable GLP-1 agents. The once-daily formulation may have improved hepatic safety. Full safety profile pending. Should only be used within clinical trials.
NOT FDA-approved. In clinical development. Not available outside clinical trials.