Efficacy and safety of danuglipron (PF ‐06882961) in adults with obesity: A randomized, placebo‐controlled, dose‐ranging phase 2b study

🥉 Top 5% JournalJun 20, 2025Diabetes, obesity & metabolism

Effectiveness and safety of danuglipron at different doses in adults with obesity

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Abstract

628 participants were randomized in a Phase 2b trial assessing the effects of danuglipron on obesity.

Danuglipron was associated with statistically significant weight reductions, with changes ranging from -5.0% to -12.9% compared to placebo.
Approximately 39.3% of participants completed the treatment, with 38% discontinuing due to adverse events (AEs).
Nausea and vomiting were the most frequently reported side effects, particularly at higher doses.
Most adverse events were classified as mild, and no notable dose-related trends were found in safety outcomes.

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AIMS: This randomized, double-blind, placebo-controlled Phase 2b study aimed to assess the efficacy, safety, and tolerability of danuglipron (PF-06882961), an oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in adults with obesity.

MATERIALS AND METHODS: Eligible participants (aged 18-75 years; with obesity, without diabetes) were randomized to receive danuglipron or placebo twice daily (BID) for 26 or 32 weeks. Danuglipron was escalated to doses of 40-200 mg BID in 1-, 2-, or 4-week intervals. Assessments included body weight, waist circumference, and safety evaluations.

RESULTS: Overall, 628 participants were randomized; of 626 receiving study treatment (placebo, n = 90; danuglipron, n = 536), 39.3% completed treatment. Approximately 38% of participants discontinued treatment because of adverse events (AEs) and 22% discontinued for other reasons. The primary endpoint was the change in weight from baseline to the end of treatment; all danuglipron groups demonstrated statistically significant reductions with least squares mean percentage decreases from baseline ranging from -5.0% (90% confidence interval [CI] -6.8%, -3.2%) to -12.9% (90% CI -16.1%, -9.5%) relative to placebo. Danuglipron was considered safe. Consistent with the mechanism, the most frequently reported events were nausea and vomiting, and increased rates of gastrointestinal AEs were generally observed at higher doses. Most events were reported as mild, and no other dose-related trends were observed in safety endpoints.

CONCLUSIONS: In participants with obesity, danuglipron resulted in statistically significant and clinically meaningful reductions in body weight versus placebo over 26 or 32 weeks. The overall safety profile observed in this study was consistent with expectations for the mechanism, although discontinuation rates due to AEs were higher than anticipated across all treatment groups, including placebo.

CLINICALTRIALS: gov identifier: NCT04707313.

Key numbers

-12.9%

Weight Reduction

Maximum weight loss observed in danuglipron 200 mg group at Week 32.

38.5%

Discontinuation Rate

Overall discontinuation rate due to all-causality adverse events.

246 of 626

Participant Completion

Number of participants who completed the double-blind treatment phase.

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Abstract

Key numbers

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