Evaluating the Evolving Real-World Adverse Events of GLP-1RAs Using FDA Adverse Event Reporting System (FAERS)

Area of Science:

• Pharmacovigilance and Drug Safety
• Real-World Evidence in Clinical Practice
• Endocrinology and Metabolism

Background:

• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and weight management.
• Understanding the full spectrum of adverse events (AEs) associated with GLP-1RAs is crucial for patient safety.
• Existing safety data may not fully capture emerging concerns in diverse patient populations and indications.

Purpose of the Study:

• To comprehensively assess the spectrum and frequency of AEs associated with GLP-1RAs.
• To identify potential differences in AE profiles based on the indication for use (diabetes vs. weight management).
• To leverage real-world data to inform clinical monitoring and future drug development.

Main Methods:

• Retrospective analysis of over 18 million US FDA Adverse Event Reporting System (FAERS) reports from 2012-2025.
• Inclusion of five commonly prescribed FDA-approved GLP-1RAs.
• Application of disproportionality analyses and subgroup analyses to detect AE signals and compare indications.

Main Results:

• A total of 137,451 FAERS reports involved GLP-1RAs.
• Gastrointestinal, nutritional/metabolic, and psychiatric disorders were the most frequent AEs.
• GLP-1RA use for diabetes was linked to retinopathy and hearing loss, while weight management use showed predominant nutritional, metabolic, and psychiatric AEs.

Conclusions:

• GLP-1RAs are associated with a wide array of AEs across different therapeutic indications.
• Clinical monitoring and long-term safety evaluations are essential for patients using GLP-1RAs.
• Real-world evidence from pharmacovigilance databases can guide safety communications and research for next-generation therapies.