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Danuglipron

Also known as PF-06882961

Not a peptide: Pfizer's oral small-molecule GLP-1 agonist, discontinued in 2025 after a liver injury case.

early-clinical Metabolic & weight research chemical

At a glance

Category
Metabolic & weight
Status
research chemical
Route
oral tablet, twice daily in the published trials
Half-life
short enough to require twice-daily dosing in the phase 2b programme; a once-daily modified-release formulation was the object of the dose-optimisation studies that were running when development stopped 12
Onset
weight change over weeks to months; the phase 2b trial ran 26 or 32 weeks 1
Sequence
None — danuglipron is not a peptide. It is a synthetic non-peptide small molecule.

Development discontinued. Danuglipron was never approved anywhere and never will be: on 14 April 2025 Pfizer announced it was ending the clinical programme for chronic weight management 2. The stated trigger was a single asymptomatic participant in a dose-optimisation study who experienced potential drug-induced liver injury, which resolved after the drug was stopped; across a safety database of more than 1,400 participants the overall frequency of liver enzyme elevation was in line with approved agents in the class, and the decision was described as following a review of the totality of the clinical data together with recent input from regulators 2. The company said it would continue with an oral GIP receptor antagonist candidate and other earlier obesity programmes 2. There is no product, no approved dose and no supply chain. Anything sold under this name is not a Pfizer product.

Doping status: Not named on the Prohibited List; falls under S0 (non-approved substances) by class description, which is an inference and not a listing

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

Danuglipron is included here for the same reason as orforglipron and MK-677: people searching for peptides run into it constantly. It is not a peptide. It is a conventional small organic molecule that binds the GLP-1 receptor and activates it, which is why it can be swallowed as an ordinary tablet rather than injected.

At the receptor the pharmacology is the familiar GLP-1 one: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying and reduced appetite through central circuits. Nothing about the mechanism failed. What failed was the molecule.

The story of danuglipron is a liver story, and it is a longer one than the April 2025 announcement suggests, because Pfizer had already lost a second oral GLP-1 candidate to the same organ. Lotiglipron (PF-07081532) was a once-daily oral small-molecule GLP-1 receptor agonist taken into a phase 2 dose-ranging study in type 2 diabetes and obesity. That study was terminated early for safety reasons after routine data review. Transaminase elevations occurred in 6.6% of the diabetes cohort and 6.0% of the obesity cohort on lotiglipron, against 1.6% on placebo in the obesity cohort, and the authors state plainly that attempts to identify the at-risk population were unsuccessful and that clinical development was terminated as a result 3. Efficacy had been demonstrated: up to -1.44% HbA1c in the diabetes cohort and up to -7.47% body weight in the obesity cohort 3.

Danuglipron then became the lead oral asset, and its own problem was different in shape. Liver enzyme elevations across the danuglipron programme were, by Pfizer's account, no more frequent than with approved GLP-1 agonists 2. What ended it was one case of apparent drug-induced liver injury in an asymptomatic participant — a signal about a single patient rather than a rate across a cohort — combined with regulatory input and a programme that had already shown poor tolerability at effective doses. Two oral small-molecule GLP-1 agonists from one company, both stopped over the liver, is the fact worth carrying away. It is not a class verdict: orforglipron, a structurally different oral small-molecule GLP-1 agonist from a different company, was approved in 2026. But it is a reminder that oral small molecules can carry hepatic liabilities that injected peptides do not.

What the research shows

Danuglipron has a published, adequately sized phase 2b obesity trial and a substantial safety database of more than 1,400 participants, and it never reached phase 3 12. The efficacy was real — up to about 13% weight loss relative to placebo over 26 to 32 weeks — and the tolerability was not: only 39.3% of participants completed treatment, and roughly 38% stopped because of adverse events 1. Read together with the liver signal, that is a compound with a genuine effect and no acceptable route to a licence.

Research in humans

The phase 2b trial (Diabetes, Obesity and Metabolism, 2025) randomised 628 adults with obesity and without diabetes to danuglipron or placebo twice daily for 26 or 32 weeks, with the dose escalated to targets of 40-200 mg twice daily over 1-week, 2-week or 4-week intervals. Least-squares mean weight reduction relative to placebo ranged from -5.0% to -12.9%. Of 626 participants who received study treatment, 39.3% completed it; approximately 38% discontinued because of adverse events and 22% for other reasons. Nausea and vomiting were the most frequent events and gastrointestinal events increased with dose. The authors describe the discontinuation rates as higher than anticipated across all treatment groups, including placebo 1. Systematic reviews have since pooled danuglipron with orforglipron in type 2 diabetes and obesity 5, and with other non-peptide GLP-1 agonists for gastrointestinal tolerability 6. Lotiglipron's phase 2 study treated 901 participants before being terminated early for safety 3; two earlier phase 1 multiple-ascending-dose studies of lotiglipron have also been published 4.

Animal and lab research

Not the decisive literature here. The compound reached large human trials, and the reasons it was abandoned are human findings — hepatic and tolerability — rather than preclinical ones. No animal work is summarised in this entry.

Caveats. All the trials were designed, funded and analysed by Pfizer, and most authors on the phase 2b paper are or were Pfizer employees 13. The programme never reached phase 3, so there is no confirmatory efficacy result, no cardiovascular outcome trial and no long-term safety data. The completion rate in the phase 2b trial was under 40%, which makes the weight-loss estimates fragile — the participants who tolerated the drug are not a random sample of those who started it. The single drug-induced liver injury case that ended the programme has not been published as a case report, so the only account of it is a company press release 2. Nothing further will be learned: the programme is closed.

What it is used for

  • None. Danuglipron has no approved indication, no ongoing development and no legitimate supply 2
  • Historically, chronic weight management in adults with obesity was the indication under study when the programme was stopped 12
  • Of continuing interest as a case study in why oral small-molecule GLP-1 agonists have been harder to develop than the mechanism suggests, and in what a single-patient liver signal can do to a programme 23

Dosing

Dose
No dose exists outside the closed trial programme. In the phase 2b obesity trial the target doses were 40-200 mg twice daily
Frequency
twice daily in the published trials
Route
Oral tablet
Duration
26 or 32 weeks in the phase 2b trial
  • The figures here describe a terminated research programme. They are not a schedule anyone should follow, and the drug was abandoned by its developer partly on tolerability grounds at exactly these doses 12.
  • Titration was tested at 1-week, 2-week and 4-week intervals to the same targets. Slower titration did not rescue the discontinuation problem: roughly 38% of participants stopped for adverse events across the trial 1.
  • The dose-optimisation studies that were running at the time the programme was stopped were testing a once-daily formulation, and Pfizer stated that a formulation and dose had been identified with potential for competitive efficacy and tolerability in phase 3 2. Those results were not published, and the numbers are not available.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

Phase 2b trial schedule (obesity, without diabetes) — terminated programme

published trial

Source: Phase 2b, ClinicalTrials.gov NCT04707313

1-week titration steps, to 26 or 32 weeksEscalated to a target of 40, 80, 120, 160 or 200 mg twice daily
2-week titration steps, to 26 or 32 weeksEscalated to a target of 120, 160 or 200 mg twice daily
4-week titration steps, to 26 or 32 weeksEscalated to a target of 80, 140 or 200 mg twice daily
26 or 32 weeksMatching placebo twice daily

628 participants randomised, 626 treated, and only 39.3% completed treatment. This schedule is recorded because it is the published one, not because it is usable: the compound was discontinued in April 2025 and no supervised version of this protocol exists anywhere.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Storage
No approved storage instruction exists, because no approved product exists.

Worked example

Not applicable. Danuglipron is an oral tablet. There is nothing to reconstitute, dissolve or inject — and there is no legitimate product to obtain in any form.

Because danuglipron is a small molecule rather than a peptide, none of the handling considerations that apply to injectable peptides — bacteriostatic water, cold chain, reconstitution stability — are relevant.

Safety

Side effects

  • Nausea and vomiting were the most frequently reported events, and gastrointestinal events were generally more frequent at higher doses 1
  • Discontinuation because of adverse events in approximately 38% of participants in the phase 2b obesity trial — the single most important safety finding, and the reason the compound was in trouble before the liver case 1
  • Potential drug-induced liver injury in one asymptomatic participant in a dose-optimisation study, which resolved after the drug was stopped; this case ended the programme 2
  • Liver enzyme elevations across more than 1,400 participants at a frequency Pfizer described as in line with approved agents of the class 2
  • The related compound lotiglipron produced transaminase elevations in 6.6% and 6.0% of its two cohorts against 1.6% on placebo, and its phase 2 study was terminated early for safety 3
  • Diarrhoea, constipation, dyspepsia and decreased appetite, as expected from GLP-1 receptor agonism
  • Long-term and rare adverse effects were never characterised, because the drug never entered phase 3

Do not use if

  • The compound is discontinued and should not be used by anyone in any circumstance. Everything below is historical rather than practical
  • Pre-existing liver disease or unexplained transaminase elevation would have been the obvious exclusion, given the reason the programme ended 23
  • Pregnancy and breastfeeding
  • History of pancreatitis
  • Severe gastrointestinal disease including gastroparesis
  • Concurrent use of another GLP-1 receptor agonist

Interactions

Never fully characterised, because development stopped before that work was completed. As a small molecule rather than a peptide, danuglipron was subject to cytochrome P450-mediated interactions in a way that injected GLP-1 peptides are not; the sister compound lotiglipron was taken through a formal interaction study against midazolam, omeprazole, dabigatran, rosuvastatin and the oral contraceptives levonorgestrel and ethinyl estradiol, which indicates the kind of interaction profile the class carries 8. Delayed gastric emptying would be expected to alter the absorption of other oral medicines. Combination with insulin or a sulfonylurea would raise hypoglycaemia risk on class grounds. None of this is actionable, since the drug does not exist as a product.

Sources