2824-LB: Indication-Specific Adverse Event Profiles of Semaglutide and Liraglutide: A FAERS Disproportionality Analysis

Introduction and Objective: In 2017, the FDA approved the glucagon-like peptide-1 (GLP-1) receptor agonists semaglutide and liraglutide for type 2 diabetes and obesity. As use increased, safety concerns emerged alongside adverse event (AE) reports. We conducted a disproportionality analysis comparing semaglutide with liraglutide across indications using the FDA Adverse Event Reporting System (FAERS). We also compared GLP-1 RA drugs as a class with metformin (for the indication of type 2 diabetes) and orlistat (for the indication of obesity) to assess whether signals were drug- or disease-related. Methods: Public FAERS quarterly files from 2017 onward were analyzed. Reports listing semaglutide, liraglutide, metformin, or orlistat as the primary suspect were included. Preferred Terms were standardized using MedDRA and grouped by System Organ Classes (SOC). Signals were identified using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). Results: Among 14,752,169 FAERS reports, 53,176 met inclusion criteria. Semaglutide generated more type 2 diabetes than obesity reports (15,515 vs 5,567); liraglutide showed a similar pattern (3,800 vs 1,284). Positive disproportionality signals occurred across SOCs for both indications when comparing semaglutide with liraglutide. In diabetes reports, semaglutide showed higher reporting odds for brain fog (ROR 12.78), optic ischemic neuropathy (12.11), impaired gastric emptying (9.57), and suicidal ideation (4.69). In obesity reports, semaglutide signals included malnutrition (10.92), ileus (6.98), insomnia (2.76), and visual impairment (2.38). Class comparisons with metformin and orlistat were consistent. Conclusion: AE signals were consistent across indications, suggesting drug-specific mechanisms may contribute more than disease factors. Because FAERS is a spontaneous reporting system, causality cannot be inferred. Disclosure S.A. Fisch: None. E.J. Neugut: None. N. Cornet: None. D. Quigee: None. A.I. Neugut: Research Support; Current; Otsuka America Pharmaceutical, Inc., Kyowa Kirin Co., Ltd. Consultant; Ended; Merck Sharp & Dohme Corp. Advisory Panel; Current; United Biosource Corp. Consultant; Current; Value Analytics. Advisory Panel; Current; Cybin. D. Freedberg: None.