Stratified analysis of the association between anti-obesity medications and digestive adverse events: a real-world study based on the FDA adverse event reporting system database.

ABSTRACT

BACKGROUND: Numerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs. METHODS: We analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis. RESULTS: Among 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI 2.42-3.6). Orlistat (ROR = 3.30, 95% CI 3.08-3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI 3.45-10.88) with phentermine-topiramate still needs further clarification. CONCLUSIONS: Tirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate's association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events.