Danuglipron
/ Oral small-molecule GLP-1 receptor agonist (Pfizer)ALIAS · PF-06882961 · Danuglipron
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Tier 2. Phase 2 obesity and type 2 diabetes data published; Phase 3 development was paused by Pfizer in 2025 following liver-enzyme elevations in long-term safety data and dose-limiting tolerability across the Phase 2 program. Not approved.
Danuglipron is an orally bioavailable small-molecule agonist of the GLP-1 receptor, structurally distinct from the peptide GLP-1 receptor agonists (semaglutide, liraglutide, exenatide). Like other small-molecule GLP-1 receptor agonists in development (orforglipron, lotiglipron), danuglipron binds an allosteric pocket of the GLP-1 receptor to stabilise the active receptor conformation. The oral route avoids the need for subcutaneous injection but requires pharmacokinetics and tolerability suitable for chronic daily oral dosing.
Tier 2. The Phase 2 obesity trial (Saxena and colleagues, NEJM 2023) reported dose-dependent weight reduction in adults with obesity over 32 weeks with twice-daily oral danuglipron. Phase 2 type 2 diabetes data showed dose-dependent HbA1c reduction. The Phase 3 program was paused in 2025 following observation of dose-limiting tolerability (notably nausea and vomiting at efficacious doses) and liver-enzyme elevations in long-term safety data.
Common adverse events in the Phase 2 program were nausea, vomiting, diarrhoea, and dyspepsia, with tolerability discontinuation rates higher than expected at the doses required for meaningful weight loss. Liver-enzyme elevations (ALT/AST) were observed in longer-term safety data and contributed to Pfizer's decision to pause Phase 3 development in 2025. Pancreatitis and class C-cell tumour signals apply to the small-molecule class as for peptide GLP-1 receptor agonists.
Regulatory status
- FDA status:
- Not FDA-approved
Pfizer's 2025 decision to pause Phase 3 development — following an earlier 2023 discontinuation of the once-daily modified-release formulation for tolerability — is the dominant practical fact. The small-molecule oral GLP-1 receptor agonist class faces an open question of whether tolerability adequate for chronic obesity and T2D dosing is achievable at efficacious exposures. Orforglipron (Lilly) is the most-advanced surviving program in the same class; lotiglipron was discontinued earlier for liver findings. Vendor 'danuglipron' research-grade material is not interchangeable with clinical-grade compound.