A comprehensive analysis of over 18 million reports uncovers differences in adverse event profiles of popular GLP-1 receptor agonists, highlighting gastrointestinal, psychiatric, and other effects that may influence clinical monitoring and patient counselling.
A large pharmacovigilance study of glucagon-like peptide-1 receptor agonists has found that their real-world safety profile varies by drug and by use, with gastrointestinal problems remaining the most common concern and signals also emerging for psychiatric, nutritional, and ophthalmic effects.
The analysis, published in Obesity and based on the US Food and Drug Administration’s Adverse Event Reporting System, examined more than 18.4 million quarterly reports filed between late 2012 and early 2025. After removing duplicate and unmappable records, the researchers identified 175,821 reports involving five widely used GLP-1 medicines, including semaglutide, dulaglutide, liraglutide, exenatide and tirzepatide. The database is intended to help regulators spot safety issues after a drug reaches the market, and the FDA updates it quarterly.
Among 137,451 usable reports tied to GLP-1 treatment, most related to diabetes, while a smaller share involved weight control or obesity treatment. Serious outcomes were recorded in a minority of cases, including hospitalisation, life-threatening events and death. The researchers said the pattern of adverse events differed depending on the reason for treatment: weight-loss use was more often linked with nutritional problems, eating disorders, depressive symptoms, suicidal or self-injurious behaviour, panic symptoms and sensory changes, while diabetes use was associated with a larger share of serious outcomes, including pancreatic and retinal complications.
The study also suggests that not all GLP-1 medicines look the same in reporting data. Semaglutide was associated with more gastrointestinal, psychiatric and nutritional signals, while dulaglutide and exenatide were linked with more reports of death and hospitalisation. Liraglutide and exenatide showed a higher proportion of neoplasm-related reports. Earlier FAERS analyses have similarly pointed to nausea, vomiting and delayed gastric emptying as recurring issues, and other recent pharmacovigilance work has also raised questions about rare ocular and psychiatric events. The authors cautioned that spontaneous reports cannot prove causation, but said the findings should help clinicians with counselling and risk monitoring as use of these drugs continues to expand.
To make the data easier to explore, the researchers have also launched a web portal that allows users to inspect additional adverse-event patterns linked to GLP-1 medicines. They argue that combining such reporting data with electronic health records, claims databases and disease registries will be essential for separating true safety signals from background noise and for understanding how benefits and harms balance out across different patient groups.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
