Evidence Grade C — Moderate human evidence. 37 published studies, 28 human. 19 registered clinical trials.
Medically reviewed by a licensed medical professional
Danuglipron is an oral GLP-1 pill developed by Pfizer — not a peptide. Its original twice-daily formulation achieved 8-13% weight loss in Phase IIb but was abandoned because over half of patients stopped treatment due to severe nausea. Pfizer attempted a once-daily reformulation but has since shifted its obesity efforts to other approaches.
Danuglipron is also known by these brand and alternate names:
37 published studies: 28 human, 2 animal, 9 in-vitro, 10 reviews
Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version.
Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
Research suggests danuglipron binds within the transmembrane region of the GLP-1 receptor, similar to orforglipron. It acts as a full agonist for the primary signalling pathway but shows partial agonism for a secondary pathway. The severe gastrointestinal tolerability issues with the original formulation suggest a pharmacokinetic challenge (rapid absorption peaks) that the reformulation aims to address.
Research suggests the Phase IIb trial (628 patients) demonstrated that the GLP-1 mechanism works through an oral small molecule, but tolerability was unacceptable: nausea affected up to 73% of patients and treatment discontinuation exceeded 50%. A potential liver safety signal added further concern. Danuglipron's trajectory illustrates that even a biologically effective compound can fail if patients cannot tolerate it. The rapidly evolving obesity competitive landscape — where efficacy below approximately 15% weight loss is increasingly considered insufficient — further diminished its commercial viability. Pfizer has pivoted to a different obesity mechanism (GIP receptor antagonism).
PeptideTrace tracks 19 registered clinical trials for Danuglipron sourced from ClinicalTrials.gov.
Study to Learn About How the Study Medicines Called PF-07976016 and PF-06882961 Are Taken Up by the Body, and if Either of Them Change How the Body Processes the Other Medicine in Otherwise Healthy Adults With Overweight or Obesity
A Study to Learn How the Study Medicine Danuglipron is Taken Up Into the Blood and If Danuglipron Changes How the Body Processes Other Study Medicines (Atorvastatin and Rosuvastatin) in Healthy Adults Who Are Overweight or Obese
A Study to Learn How Different Amounts of the Study Medicine Danuglipron Are Taken up Into the Blood in Otherwise Healthy Adults With Overweight or Obesity
Study to Learn How Different Forms of The Study Medicine Called Danuglipron Are Taken up Into the Blood In Healthy Adults
STUDY TO EVALUATE THE EFFECT OF PF-06882961 ON SINGLE DOSE ATORVASTATIN, MEDAZOLAM AND ORALCONTRACEPTIVE PHARMACOKINETICS IN HEALTHY ADULT PARTICIPANTS
Danuglipron (PF-06882961) is an oral non-peptide small-molecule GLP-1 receptor agonist developed by Pfizer. NOTE: This is NOT a peptide. Molecular formula: C31H30FN5O4; molecular weight 555.61 Da. CAS number: 2230198-02-2. The compound was originally developed as a twice-daily oral formulation, with subsequent exploration of a once-daily modified-release version. However, Pfizer announced full discontinuation of the danuglipron program on April 14, 2025, following a potential drug-induced liver injury case and insufficient competitive positioning in the rapidly evolving obesity landscape.
Research suggests danuglipron binds within the transmembrane helices of GLP-1R, requiring the primate-specific Trp33 residue for receptor engagement. The compound acts as a full agonist for cAMP signaling (EC50 = 13 nM) but demonstrates partial agonism for beta-arrestin 2 recruitment (EC50 = 490 nM, Emax = 36%), exhibiting inherent Gs-pathway bias. This biased signaling profile was expected to prolong pharmacological activity by reducing receptor internalization and desensitization.
Research suggests the Phase 2b obesity trial (NCT04707313; N=628) demonstrated placebo-adjusted weight loss of -5.0% to -9.5% at 26 weeks and -8.2% to -12.9% at 32 weeks depending on dose and titration schedule. However, treatment discontinuation rates exceeded 50% across danuglipron arms, with nausea affecting up to 73% and vomiting 47% of participants. The twice-daily formulation was not advanced to Phase 3 due to tolerability concerns. A once-daily modified-release formulation was explored, but a potential drug-induced liver injury case combined with regulatory feedback led to full program discontinuation on April 14, 2025.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity. In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
Evidence Reviews
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
