Real-world safety comparison of liraglutide and semaglutide in weight management: Insights from European pharmacovigilance data

Background: In recent years, the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), as liraglutide and semaglutide, for weight management has significantly risen. Even if these medications are effective, some concerns remain about their safety profiles, particularly regarding long-term adverse events (AEs). This study provides an evaluation of the safety profiles of liraglutide and semaglutide in a real-world setting. Methods: A retrospective case-non-case study was conducted using data from the EudraVigilance database. All cases involving liraglutide or semaglutide used for weight management and collected in the database between January 2018 and December 2023 were analyzed. Disproportionality analysis was performed to assess the reporting odds ratios for events of interest (gastrointestinal events, pancreatitis, gallbladders disorders, psychiatric events, and gallbladder, pancreatic or thyroid tumors) reported at least three times. Results: A total of 27,639 cases were identified. Most cases occurred in female patients aged 18–64 years. Most reported AEs were not-serious. Gastrointestinal events were the most common, with nausea, vomiting, and diarrhea leading the list. Two events were related to gallbladder tumors. Disproportionality analysis revealed that liraglutide was associated with a higher reporting frequency of pancreatitis, gallbladder disorders, and thyroid tumors, while semaglutide showed a greater likelihood of vomiting and abdominal pain. No significant differences were found for other common gastrointestinal events, pancreatic tumors, depression, or suicidal ideation. Conclusions: Liraglutide and semaglutide showed distinct safety profiles when used for weight management. These findings highlight the importance of considering individual patient profiles and potential risks when prescribing these medications for weight management. Further real-world studies are needed to explore long-term safety and to clarify the potential association between GLP-1 RAs and malignancies.