PHARMACOVIGILANCE SIGNALS OF SEMAGLUTIDE AND OTHER GLP-1 RECEPTOR AGONISTS: AN ANALYSIS OF THE FOOD AND DRUG ADMINISTRATION (FDA) ADVERSE EVENTS REPORTING SYSTEM (FAERS) DATASET

Background: Semaglutide is a medication used to treat type 2 diabetes and obesity, belonging to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists [1]. GLP-1 is a hormone released in the intestine during the digestion of food helping to regulate blood sugar levels by stimulating the release of insulin. Semaglutide mimics the actions of GLP-1, leading to increased insulin release and decreased glucagon release, which in turn helps lower blood sugar levels, reducing appetite and food intake, leading to weight loss [2]. Moreover, recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people [3-5], issue facilitated by the putative acquisition of medications from rogue websites. Aims & Objectives: to determine the available pharmacovigilance misuse/abuse signals relating to semaglutide versus other GLP-1-receptor agonists, e.g. albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide, by analyzing the Food and Drug Administration’ s FDA Adverse Events Reporting System (FAERS) pharmacovigilance dataset. Method: A descriptive analysis of the characteristics of Adverse Event Reports (AER), including sociodemographic data, country of origin, and concomitant licit/illicit substances, was performed here. Pharmacovigilance measures, including reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and Bayesian empirical geometric mean (EBGM), were calculated, using the R package PhViD. Results: From January 2018 to December 2022, a total of 31,439 AERs involving the selected molecules were submitted to FAERS, being the most represented: dulaglutide (37.6%), semaglutide (26.1%), and liraglutide (25.0%). Regarding Semaglutide an increase in the number of reported AERs compared to remaining molecules was observed; overall, most reports came from the US and involved female adults. Drug misuse-, abuse-, and withdrawal-related AERs were most typically reported for semaglutide compared with the other selected GLP-1 analogues. Specifically, ‘drug abuse’, ‘drug withdrawal syndrome’, and ‘prescription drug used without a prescription’ were reported >3.50 times as frequently (e.g., PRR values were 4.05, 4.05, and 3.60, respectively; FDR