Liver Injury Ends Development of Pfizer’s Oral GLP-1 for Obesity

Pfizer has stopped clinical development of danuglipron (PF-06882961), its once-daily oral glucagon-like peptide-1 receptor agonist (GLP-1) candidate to treat obesity. Danuglipron was being studied for adults with obesity and without type 2 diabetes.

Pfizer’s two dose-optimization studies of once-daily formulations of danuglipron met key pharmacokinetic objectives and confirmed a formulation and dose to be used in a phase 3 trial, according to a news release.

Company executives said that the overall frequency of elevated liver enzymes across the more than 1,400 participants in the clinical development program of danuglipron was in line with approved drugs in the class. But in one of the dose optimization studies, an asymptomatic patient experienced potential drug-induced liver injury, which resolved after discontinuation of danuglipron.

“After a review of the totality of information, including all clinical data generated to date for danuglipron and recent input from regulators, Pfizer has decided to discontinue development of the molecule,” the company said in the release.

The company plans to either publish the data from these trials or present them at a scientific meeting.

Related: Pfizer Stops GLP-1 Obesity Trial Because of High Discontinuation Rates

In December 2023, Pfizer announced that it had stopped a phase 2 trial for a twice-daily danuglipron. The company had said the study met its primary endpoint, demonstrating statistically significant change in body weight from baseline. But more than 50% of patients discontinued treatment across all doses compared with about 40% with placebo.

At that time, Pfizer had indicated there were no new safety signals and treatment with danuglipron was not associated with increased incidence of liver enzyme elevation compared with placebo. Most adverse events were mild and gastrointestinal in nature.

A Pfizer spokesperson has confirmed that the company has canceled the clinical development of danuglipron, including for diabetes. Pfizer’s pipeline update from February 2025 shows that danuglipron was also in development to treat patients with type 2 diabetes.

Meanwhile, Pfizer is conducting a phase 2 trial of PF-07976016, an oral GIPR antagonist. Research has suggested that blocking glucose-dependent insulinotropic polypeptide (GIP) can stimulate insulin production, which can stimulate weight loss.