Danuglipron
Investigational oral small-molecule GLP-1 receptor agonist developed by Pfizer. Showed weight-loss efficacy in trials but development was complicated by tolerability and a liver-safety signal.
01 Overview
Danuglipron (PF-06882961) is a non-peptide, orally bioavailable GLP-1 receptor agonist. Unlike injectable peptides, it is a small molecule intended for daily oral dosing, part of the wave of oral incretin drugs aiming to broaden access.
Phase 2 trials showed meaningful weight loss, but high rates of gastrointestinal adverse events and, later, a case of drug-induced liver injury led Pfizer to discontinue the once-daily formulation and reassess the programme. It illustrates the tolerability and safety challenges of oral small-molecule GLP-1 agonists.
02 Mechanism
Orally active small-molecule agonist of the GLP-1 receptor, stimulating glucose-dependent insulin secretion and appetite suppression.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Trial dose | 80–200 mg/day | Oral | Ranges explored in Phase 2b; formulation and schedule varied |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Weight lossDose-dependent weight loss in Phase 2b obesity trials. | ~4-9% | Clinical | |
| Improved glycaemic controlReduced HbA1c in type 2 diabetes cohorts. | HbA1c reduction | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal intoleranceHigh rates of nausea and vomiting, contributing to discontinuations. | Moderate | Very common | Clinical | |
| Elevated liver enzymesTransaminase elevations and a reported case of drug-induced liver injury. | Severe | Rare | Clinical |