GLP-1 & Metabolic Research
Preliminary
Danuglipron
Twice-daily oral small molecule GLP-1 receptor agonist (Pfizer). Studied as pill-format GLP-1 alternative. Phase 3 program paused 2024 due to GI tolerability; research continues on modified release formulations.
GLP-1oralPfizersmall moleculeweight lossBIDtwice-daily
Half-life
4–6 hours; requires twice-daily dosing
SKUs
2
Evidence
Preliminary
Danuglipron is an oral, small-molecule GLP-1 receptor agonist being developed by Pfizer. Unlike injectable GLP-1 peptides, danuglipron is taken by mouth as a pill. It was studied in phase 2 trials for type 2 diabetes and obesity. However, Pfizer announced in 2024 that it was discontinuing once-daily danuglipron development after phase 2b results due to the incidence of liver enzyme elevations seen in the trial.
Oral GLP-1 Research
Danuglipron represents part of the effort to develop small-molecule oral alternatives to injectable GLP-1 receptor agonists. Phase 1 and phase 2 trials confirmed it activates the GLP-1 receptor and produces weight loss and blood sugar improvements consistent with the mechanism.
Weight Management
Phase 2 data showed dose-dependent weight reduction in participants, consistent with GLP-1 receptor activation. The oral format was seen as potentially offering a more accessible option for patients who prefer not to inject.
Type 2 Diabetes
Danuglipron was studied for HbA1c reduction in type 2 diabetes patients. Results showed improvements in blood sugar markers consistent with other GLP-1 agonists.
- Phase 2 data confirmed weight reduction and blood sugar improvements consistent with GLP-1 receptor activation.
- Oral small-molecule format was validated as pharmacologically active at the GLP-1 receptor.
- Development was discontinued by Pfizer in 2024 due to liver enzyme elevations observed in the phase 2b trial.
- GI side effects were consistent with the GLP-1 class.
Danuglipron development was discontinued by Pfizer following liver enzyme signals in the phase 2b trial. This is the most important piece of context for this compound — it is not moving forward toward approval. The liver enzyme findings are a meaningful safety signal that distinguishes it from approved GLP-1 medications. It is not approved for any use.
Most GLP-1 receptor agonists are peptides — chains of amino acids — that need to be injected because they would be broken down by digestive enzymes if swallowed. Danuglipron is a small chemical molecule, not a peptide, which allows it to survive digestion and be absorbed from the gut into the bloodstream as a pill. Once in circulation, it finds and activates the GLP-1 receptor the same way that injectable GLP-1 agonists do — slowing stomach emptying, reducing appetite, and improving insulin signaling. The pharmacological effect is similar; the challenge has been achieving consistent blood levels from an oral form and, as the trial showed, managing off-target effects on the liver.
Pfizer discontinued danuglipron in 2024 after phase 2b data showed liver enzyme elevations (elevated transaminases) in some participants, raising hepatotoxicity concerns. This is an unresolved safety issue. It is not FDA-approved and is not being actively developed for the previously planned indications.
Preliminary
Most evidence comes from preclinical studies and case reports. Human data is limited and more research is needed.
Published Research Ranges
40–120mg twice daily in phase 2 dose-finding; 120mg BID in phase 3 pivot
Research Context Only: These are ranges reported in published scientific studies for educational reference. They are not dosing recommendations. This is not medical advice. Always consult a qualified healthcare professional.
Sources listed here are from the platform research library. All links open the original publication. No citations are generated by AI.
Danuglipron (PF-06882961), an Oral GLP-1 Receptor Agonist, in Type 2 Diabetes: Phase 2
Nature Medicine • 2022
• DOI: 10.1038/s41591-022-01908-3
View Source
Oral Small-Molecule GLP-1 Agonists in Development: Pharmacology and Clinical Progress
Cell Metabolism • 2023
• DOI: 10.1016/j.cmet.2023.04.013
View Source
Non-clinical and first-in-human characterization of ECC5004/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist
• 2025
• DOI: 10.1111/dom.16047
View Source
Efficacy and safety of danuglipron (PF-06882961) in adults with obesity: A randomized, placebo-controlled, dose-ranging phase 2b study
• 2025
• DOI: 10.1111/dom.16534
View Source
Efficacy and Safety of Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron for Glycemic Control Among Patients With Type 2 Diabetes: A Randomized Clinical Trial
• 2023
• DOI: 10.1001/jamanetworkopen.2023.14493
View Source
Tolerability, safety and pharmacodynamics of oral, small-molecule glucagon-like peptide-1 receptor agonist danuglipron for type 2 diabetes: A 12-week, randomized, placebo-controlled, Phase 2 study comparing different dose-escalation schemes
• 2023
• DOI: 10.1111/dom.15168
View Source
A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of danuglipron (PF-06882961), an oral small-molecule glucagon-like peptide-1 receptor agonist, in Japanese adults with type 2 diabetes mellitus
• 2023
• DOI: 10.1111/dom.14928
View Source
Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial
• 2021
• DOI: 10.1038/s41591-021-01391-w
View Source
Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review
• 2024
• DOI: 10.1089/thy.2023.0530
View Source
Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials
• 2023
• DOI: 10.1016/j.metabol.2023.155710
View Source
Oral GLP-1-Based Therapeutics in the Obesity-Metabolic Syndrome-Diabetes Continuum: Translational Advances, Clinical Barriers, and Emerging Strategies
• 2026
• DOI: 10.3390/ph19050732
View Source
Medical therapy to treat obesity and optimize fertility in women of reproductive age: a narrative review
• 2025
• DOI: 10.1186/s12958-024-01339-y
View Source
Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies
• 2025
• DOI: 10.4093/dmj.2025.0106
View Source
Anti-obesity peptides from food: Production, evaluation, sources, and commercialization
• 2025
• DOI: 10.1111/1541-4337.70158
View Source
From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics
• 2025
• DOI: 10.1016/j.neurot.2025.e00712
View Source
GLP-1/GLP-1R axis: from metabolism (obesity and T2DM) to immunity
• 2025
• DOI: 10.1098/rsob.240303
View Source
Protein-Ligand Interactions in Cardiometabolic Drug Targets: Focus on Weight Loss and Cardioprotection
• 2025
• DOI: 10.3390/molecules30214240
View Source
Clinical studies on anti-obesity medications in Arab countries
• 2025
• DOI: 10.15537/smj.2025.46.5.20250126
View Source
Immunometabolic crossroads: infections as bidirectional modulators in diabetes and metabolic syndromes
• 2025
• DOI: 10.3389/fendo.2025.1710157
View Source
2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025
• 2025
• DOI: 10.2337/dc25-s002
View Source
Childhood obesity from the genes to the epigenome
• 2024
• DOI: 10.3389/fendo.2024.1393250
View Source
Recent achievements and future directions of anti-obesity medications
• 2024
• DOI: 10.1016/j.lanepe.2024.101100
View Source
Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy
• 2024
• DOI: 10.3390/ijms25158202
View Source
Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease: Opportunities and challenges
• 2024
• DOI: 10.4254/wjh.v16.i5.731
View Source
Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article
• 2024
• DOI: 10.4103/ijem.ijem_442_23
View Source
Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy
• 2023
• DOI: 10.1007/s00125-023-05929-0
View Source
GLP-1R Signaling and Functional Molecules in Incretin Therapy
• 2023
• DOI: 10.3390/molecules28020751
View Source
Glucagon-Like Peptide-1 Receptor Agonists for Chronic Weight Management
• 2023
• DOI: 10.1155/2023/9946924
View Source
Applications of oxetanes in drug discovery and medicinal chemistry
• 2023
• DOI: 10.1016/j.ejmech.2023.115802
View Source
Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial
• 2023
• DOI: 10.1016/s2213-8587(22)00387-4
View Source
Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X)
• 2013
• DOI: 10.2337/dc12-2709
View Source
Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin
• 2013
• DOI: 10.1111/dom.12076
View Source
Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia)
• 2012
• DOI: 10.1111/j.1463-1326.2012.01618.x
View Source
Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and β-cell Function in type 2 diabetic patients
• 2013
• DOI: 10.2337/db12-1762
View Source
Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis
• 2021
• DOI: 10.1001/jamacardio.2020.4511
View Source
Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis
• 2017
• DOI: 10.1111/dom.12805
View Source
Advances in GLP-1 receptor agonists delivery systems for obesity and diabetes
• 2026
• DOI: 10.1016/j.apsb.2026.01.035
View Source
Obesity and emerging intervention strategies: Mechanistic insights and novel drug targets
• 2026
• DOI: 10.1097/cm9.0000000000003919
View Source
Clinical development of oral semaglutide for the treatment of type 2 diabetes mellitus: focusing on early phase clinical trials
• 2025
• DOI: 10.12793/tcp.2025.33.e3
View Source
Efficacy and safety of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease: An updated review
• 2025
• DOI: 10.3748/wjg.v31.i37.111435
View Source
The Obesity Drug Revolution: New Frontiers in Pharmacotherapy
• 2025
• DOI: 10.7759/cureus.96713
View Source
Recent advances associated with cardiometabolic remodeling in diabetes-induced heart failure
• 2024
• DOI: 10.1152/ajpheart.00539.2024
View Source
Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes?
• 2024
• DOI: 10.1530/joe-23-0339
View Source
Research Progress on Peptide Drugs for Type 2 Diabetes and the Possibility of Oral Administration
• 2024
• DOI: 10.3390/pharmaceutics16111353
View Source
Evaluating Glycemic Control Efficacy and Safety of the Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis
• 2023
• DOI: 10.2147/dmso.s439587
View Source
Potential Therapeutic Strategies in the Treatment of Metabolic-Associated Fatty Liver Disease
• 2023
• DOI: 10.3390/medicina59101789
View Source
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
• 2023
• DOI: 10.1038/s41392-023-01588-0
View Source
Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems
• 2023
• DOI: 10.1038/s41573-023-00670-0
View Source
Achieving end-to-end success in the clinic: Pfizer's learnings on R&D productivity
• 2022
• DOI: 10.1016/j.drudis.2021.12.010
View Source
Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease
• 2021
• DOI: 10.2147/dddt.s315724
View Source
Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies
• 2021
• DOI: 10.1016/j.expneurol.2020.113518
View Source
Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?
• 2021
• DOI: 10.3389/fimmu.2021.678744
View Source
Contemporary Classification of Glucagon-Like Peptide 1 Receptor Agonists (GLP1RAs)
• 2021
• DOI: 10.1007/s13300-021-01113-y
View Source
GLP-1 receptor agonists: an updated review of head-to-head clinical studies
• 2021
• DOI: 10.1177/2042018821997320
View Source
Ten things to know about ten cardiovascular disease risk factors
• 2021
• DOI: 10.1016/j.ajpc.2021.100149
View Source
Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain
• 2021
• DOI: 10.1007/s40265-021-01579-x
View Source
The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD)
• 2020
• DOI: 10.1155/2020/3920196
View Source
60 sources · Platform research library · Not generated by AI
DAN4DAN12
Combination use is not endorsed - provided for research context only.
Want More Detailed Research?
Ask the AI anything about Danuglipron - mechanisms, trial summaries, pharmacokinetics, and comparisons.
Ask AI About Danuglipron
Research Education Only: This profile is for educational purposes only. All information is sourced from published scientific literature. This is not medical advice. Not for human consumption. Consult qualified medical professionals for any health decisions.