Danuglipron
Danuglipron (oral small-molecule GLP-1 agonist)
Pfizer's oral small-molecule GLP-1 agonist whose development was discontinued after tolerability and safety signals.
Overview
Danuglipron was Pfizer's attempt at an oral small-molecule GLP-1 agonist to compete with injectable peptides. Despite showing weight loss in trials, the program faced high rates of gastrointestinal side effects and a liver-enzyme safety signal, and Pfizer discontinued its development. It is included as an instructive example of the challenges of oral GLP-1 drugs.
Mechanism of action
Activates the GLP-1 receptor as an orally available small molecule rather than an injected peptide.
Key studies & citations
- Human2021
Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial
First-in-patient study of the oral small-molecule GLP-1 agonist, showing glucose lowering and weight loss.
Nature Medicine - Human2023
Efficacy and safety of oral small molecule GLP-1 receptor agonist danuglipron for glycemic control among patients with type 2 diabetes: a randomized clinical trial
Reduced HbA1c, fasting glucose and body weight at 16 weeks versus placebo.
JAMA Network Open - Human2025
Efficacy and safety of danuglipron (PF-06882961) in adults with obesity: a randomized, placebo-controlled, dose-ranging phase 2b study
Clinically meaningful weight loss over 26 to 32 weeks, but discontinuations for adverse events were higher than anticipated in all groups.
Diabetes, Obesity and Metabolism - Human2025
Pfizer provides update on oral GLP-1 receptor agonist danuglipron
April 14, 2025: development discontinued after a case of potential drug-induced liver injury in a dose-optimization study.
Pfizer press release
Frequently asked questions
Why was danuglipron discontinued?
It was dropped after tolerability problems and a liver-enzyme safety signal, illustrating how hard oral GLP-1 drugs are to get right.