Indication-specific adverse event profiles of semaglutide and liraglutide: a FAERS disproportionality analysis

Objective By 2021, regulatory agencies had approved two glucagon-like peptide-1 receptor agonists (GLP-1RAs), semaglutide and liraglutide, for the treatment of type 2 diabetes and obesity. Since then, concerns have emerged about whether adverse events (AEs) differ by GLP-1RA or indication. Research design and methods We analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) reports (2021–2025) to compare adverse events associated with semaglutide and liraglutide indications. Comparisons with metformin and orlistat helped distinguish drug-related signals from disease-related signals. We defined safety signals by a positive reporting odds ratio and at least one other positive disproportionality metric. Results Among 8,213,105 FAERS reports, 33,259 met the inclusion criteria. Semaglutide generated more reports for type 2 diabetes than for obesity (13,168 vs. 5,444), and liraglutide showed a similar pattern (1,201 vs. 837). GLP-1RAs exhibited gastrointestinal AEs. Semaglutide showed signals for slowed gastrointestinal motility across both indications, particularly impaired gastric emptying, in both type 2 diabetes and obesity reports (ROR = 8.35, 95% CI = 1.16–59.97 and ROR = 4.01, 95% CI = 2.12–7.58, respectively). Liraglutide demonstrated signals for more severe gastrointestinal AEs, including abdominal distention in type 2 diabetes (ROR = 1.46, 95% CI = 1.12–1.91) and pancreatitis in obesity (ROR = 2.90, 95% CI = 1.91–4.39) reports. Additional notable safety signals included optic ischemic neuropathy with semaglutide (ROR = 4.42, 95% CI = 1.41–13.87) and psychiatric AEs, including suicidal ideation (ROR = 5.98, 95% CI = 1.24–24.19). Conclusion We identified robust signals for GLP-1RAs, including impaired gastric emptying, ileus, and ischemic optic neuropathy. Additionally, we identified signals for suicidal ideation. Future studies are needed to evaluate for causal relationships.