Characterizing the Adverse Event Profile of Semaglutide: A Comprehensive U.S. Food and Drug Administration Adverse Event Reporting System-Based Pharmacovigilance Study.
TL;DR
Semaglutide is primarily associated with gastrointestinal and metabolic adverse events consistent with its pharmacological effects; however, several less common but potentially important safety signals were identified, highlighting the need for continued pharmacovigilance and careful clinical monitoring in real-world use.
Abstract
Background
Semaglutide, a glucagon-like peptide-1 receptor agonist, is increasingly used for the management of type 2 diabetes mellitus and obesity. Given its expanding clinical use, a comprehensive evaluation of its safety profile using real-world data is warranted. This study aimed to characterize adverse event signals associated with semaglutide using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).
Methods
Adverse event reports associated with semaglutide were extracted from the FAERS database from 2004 Q1 to 2025 Q3. After data extraction and screening, cases in which semaglutide was recorded as the primary suspected drug were included. Adverse events were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) at the preferred term (PT) and system organ class (SOC) levels. Signal detection was performed using disproportionality methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), relative reporting ratio (RRR), and empirical Bayes geometric mean (EBGM).
Results
A total of 43,754 reports were identified. Gastrointestinal disorders were the most frequently reported system organ class, with nausea (n = 5,637; 12.88%), vomiting (n = 4,097; 9.36%), diarrhoea (n = 3,276; 7.49%) and constipation (n = 2,257; 5.16%) being the most frequently reported adverse events. Impaired gastric emptying (n = 2,200; 5.03%) showed a markedly elevated reporting signal. Significant signals were also observed for metabolic and nutritional events, including decreased appetite (n = 2,221; 5.08%), dehydration (n = 1,231; 2.81%) and diabetic ketoacidosis. Notably, high disproportionality signals were detected for weight loss poor and optic ischaemic neuropathy. Additional signals involved psychiatric, renal and hepatobiliary systems. The consistency of findings across multiple statistical methods, including empirical Bayes geometric mean, supports the robustness of the detected signals.
Conclusion
Semaglutide is primarily associated with gastrointestinal and metabolic adverse events consistent with its pharmacological effects; however, several less common but potentially important safety signals were identified. These findings highlight the need for continued pharmacovigilance and careful clinical monitoring in real-world use.