Danuglipron
Also known as: PF-06882961
Pfizer's once-failed attempt at an oral GLP-1 weight loss pill (code name PF-06882961). Despite producing meaningful weight loss in Phase 2 trials, Pfizer discontinued development in 2025 after reports of potential liver injury in a healthy volunteer. Included here because it remains heavily searched as the cautionary tale of the oral GLP-1 race — and because Pfizer is now developing alternative oral GLP-1 candidates after the danuglipron setback.
Dosage
Discontinued — Phase 2 used 40-200 mg oral twice daily
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Administration
Oral (tablet, twice daily, with food) — development discontinued
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Effects
Weight Loss
Meaningful weight loss in Phase 2 — but development discontinued in 2025 over potential liver injury.
Glycemic Control
HbA1c reductions in Phase 2 type 2 diabetes trials before discontinuation.
Oral Bioavailability
Small-molecule oral GLP-1 with no food/water restrictions, twice-daily dosing.
GI Tolerability
Over 70% of trial participants experienced nausea — major tolerability problem.
Mechanism of Action
Danuglipron (PF-06882961) is a non-peptide small molecule GLP-1 receptor agonist designed for oral administration without the food and water restrictions that limit Rybelsus (oral semaglutide). As a small molecule rather than a peptide, it is not destroyed by gastric acid or proteolytic enzymes, allowing flexible oral dosing.
The molecule binds the GLP-1 receptor outside the orthosteric peptide-binding pocket, producing biased agonism that activates the same downstream G-protein signalling as native GLP-1 — glucose-dependent insulin secretion, glucagon suppression, slowed gastric emptying, and central appetite regulation through hypothalamic and brainstem GLP-1 receptors. The key engineering feature is its short pharmacokinetic profile, with a half-life around 6-9 hours, designed for twice-daily dosing rather than once-daily exposure to limit peak plasma concentrations and improve gastrointestinal tolerability.
In Phase 2 obesity and type 2 diabetes trials, danuglipron produced meaningful weight loss and HbA1c reductions, validating the small-molecule oral GLP-1 concept. However, gastrointestinal tolerability was problematic — over 70% of trial participants experienced nausea — and the program was ultimately discontinued by Pfizer in 2025 following a single case of suspected drug-induced liver injury in a healthy volunteer. Pfizer pivoted to alternative oral GLP-1 candidates with reduced hepatic exposure profiles. Danuglipron remains a high-search-volume topic because of its prominent failure and because it set early benchmarks for what oral small-molecule GLP-1 drugs (notably orforglipron from Eli Lilly) needed to beat to succeed.
Regulatory Status
Never approved. Pfizer discontinued development in 2025 following a suspected case of drug-induced liver injury in a healthy volunteer. Pfizer continues developing alternative oral GLP-1 candidates.
Risks & Safety
Serious
a single case of potential drug-induced liver injury in a healthy volunteer led Pfizer to discontinue development in 2025 despite efficacy data.
Rare
standard GLP-1 class warnings (thyroid C-cell tumour signal, pancreatitis) plus the liver-injury signal that ended its development.
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Research Papers
5Published: September 1, 2025
AI Summary
In Pfizer's phase 2b obesity trial, danuglipron produced 5-13% weight loss versus placebo over 26-32 weeks in 628 adults. However, about 38% of patients stopped treatment due to side effects (mainly nausea and vomiting), higher than anticipated; Pfizer later discontinued the program.
Published: December 10, 2025
AI Summary
A meta-analysis of 8 trials (1,454 patients) found danuglipron lowered HbA1c by ~0.9% and body weight by ~2.2 kg in type 2 diabetes and obesity. Both danuglipron and orforglipron caused more gastrointestinal side effects than placebo.
Published: December 26, 2025
AI Summary
A meta-analysis found patients on oral danuglipron and orforglipron had ~4x higher odds of gastrointestinal side effects than placebo, with nausea most common. No clear dose-dependent worsening was observed.
Published: March 11, 2026
AI Summary
This Endocrine Reviews paper covers the next wave of GLP-1-based drugs, including the oral small-molecule agonists danuglipron and orforglipron. It frames them as steps toward more patient-friendly delivery rather than approved replacements for semaglutide.
Published: February 9, 2026
AI Summary
A computational chemistry paper that uses danuglipron's high-profile clinical failure as a case study, suggesting fragment-guided in silico modelling could have flagged the problems earlier. The paper itself is about drug discovery methodology rather than danuglipron efficacy.
Frequently Asked Questions
What is Danuglipron?
Pfizer's once-failed attempt at an oral GLP-1 weight loss pill (code name PF-06882961). Despite producing meaningful weight loss in Phase 2 trials, Pfizer discontinued development in 2025 after reports of potential liver injury in a healthy volunteer. Included here because it remains heavily searched as the cautionary tale of the oral GLP-1 race — and because Pfizer is now developing alternative oral GLP-1 candidates after the danuglipron setback.
What is Danuglipron used for?
Pfizer's once-failed attempt at an oral GLP-1 weight loss pill (code name PF-06882961). Despite producing meaningful weight loss in Phase 2 trials, Pfizer discontinued development in 2025 after reports of potential liver injury in a healthy volunteer. Included here because it remains heavily searched as the cautionary tale of the oral GLP-1 race — and because Pfizer is now developing alternative oral GLP-1 candidates after the danuglipron setback.
What is the dosage for Danuglipron?
Phase 2 trials: 40-200 mg oral twice daily, taken with food. Stepwise dose escalation over several weeks. Phase 3 development was halted in 2025; no approved dosing exists.
What are the side effects of Danuglipron?
Common in trials: nausea (notably high incidence — over 70% of patients in Phase 2), vomiting, diarrhea, headache. Serious: a single case of potential drug-induced liver injury in a healthy volunteer led Pfizer to discontinue development in 2025 despite efficacy data. Rare: standard GLP-1 class warnings (thyroid C-cell tumour signal, pancreatitis) plus the liver-injury signal that ended its development.
How does Danuglipron work?
Danuglipron (PF-06882961) is a non-peptide small molecule GLP-1 receptor agonist designed for oral administration without the food and water restrictions that limit Rybelsus (oral semaglutide). As a small molecule rather than a peptide, it is not destroyed by gastric acid or proteolytic enzymes, allowing flexible oral dosing. The molecule binds the GLP-1 receptor outside the orthosteric peptide-binding pocket, producing biased agonism that activates the same downstream G-protein signalling as native GLP-1 — glucose-dependent insulin secretion, glucagon suppression, slowed gastric emptying, and central appetite regulation through hypothalamic and brainstem GLP-1 receptors. The key engineering feature is its short pharmacokinetic profile, with a half-life around 6-9 hours, designed for twice-daily dosing rather than once-daily exposure to limit peak plasma concentrations and improve gastrointestinal tolerability. In Phase 2 obesity and type 2 diabetes trials, danuglipron produced meaningful weight loss and HbA1c reductions, validating the small-molecule oral GLP-1 concept. However, gastrointestinal tolerability was problematic — over 70% of trial participants experienced nausea — and the program was ultimately discontinued by Pfizer in 2025 following a single case of suspected drug-induced liver injury in a healthy volunteer. Pfizer pivoted to alternative oral GLP-1 candidates with reduced hepatic exposure profiles. Danuglipron remains a high-search-volume topic because of its prominent failure and because it set early benchmarks for what oral small-molecule GLP-1 drugs (notably orforglipron from Eli Lilly) needed to beat to succeed.
How is Danuglipron administered?
Danuglipron is administered via oral (tablet, twice daily, with food) — development discontinued.
What is the half-life of Danuglipron?
The half-life of Danuglipron is Approximately 6-9 hours, designed for twice-daily oral dosing.
Is Danuglipron legal?
Never approved. Pfizer discontinued development in 2025 following a suspected case of drug-induced liver injury in a healthy volunteer. Pfizer continues developing alternative oral GLP-1 candidates.
Sources. This profile is built from peer-reviewed papers indexed on PubMed, FDA-approved labelling where available, and published clinical guidelines. The 5 primary sources used are listed in the Research Papers section above, each linked to its PubMed entry. See our editorial standards for how we research and review peptide profiles.
Last reviewed. by the Peptide Reference Editorial Team. Spot an error? Email a correction.
Not medical advice. Information on this page is for educational and research reference only. Many peptides covered are not approved for human use. See our full medical disclaimer.
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