Tracking the Dynamic Trajectories: A Global-to-Local Pharmacovigilance Analysis of GLP-1 Receptor Agonists

Although GLP-1/GIP receptor agonists demonstrate unprecedented weight-loss efficacy, their rapid clinical adoption has revealed significant real-world tolerability challenges. To evaluate their dynamic safety profiles, we developed a macro-to-micro pharmacovigilance framework by combining global FAERS reports with local UT-Physician EHR. Macroscopically, we distilled 17 shared adverse events across the drug class from FAERS with disproportionality analysis. Microscopically, local EHR data (289,655 longitudinal treatment sessions across 71,316 patients) revealed 51.6% of GLP-1 sessions terminated within 90 days. Furthermore, temporal-stratified logistic regression demonstrated that initial exposure (0–30 days) correlated strongly with nausea and vomiting, which attenuated in extended sessions, whereas extended exposure (>2 years) uncovered late-onset risks, notably incident hepatic steatosis. Ultimately, this time-aware framework reveals that GLP-1 safety profiles are profoundly duration-dependent, providing critical insights into both acute intolerances and long-term medication safety.