OBJECTIVES: The phentermine/topiramate combination represents one of the most effective anti-obesity therapies under investigation; however, its safety profile requires further exploration. This study aimed to systematically analyze adverse events (AEs) associated with phentermine/topiramate using the FDA Adverse Event Reporting System (FAERS) database, identify potential safety signals, and provide evidence to inform safer clinical decision-making.
METHODS: Reports related to phentermine/topiramate were extracted from the FAERS database covering the period between the third quarter of 2012 and the fourth quarter of 2024. After data cleaning and standardization, four signal detection methods were applied separately to analyze adverse events: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS).
RESULTS: A total of 5173 AE reports associated with phentermine/topiramate were identified, encompassing 23 System Organ Class (SOC) categories. Among these, 104 Preferred Terms (PTs) met the criteria across all four signal detection algorithms. The top 30 PTs with the highest signal strength are summarized in Table 2. Symptoms listed in the prescribing information were broadly categorized into three groups: ocular disorders, emotional and psychological disorders, and metabolic disorders. Moreover, several PTs-including polycystic ovary syndrome (PCOS) (ROR 272.43), tongue bleeding (ROR 15.15), binge eating (ROR 59.39), and impaired glucose tolerance (ROR 11.75)-emerged as novel safety signals not previously documented in the prescribing information.
CONCLUSIONS: The phentermine/topiramate combination demonstrates significant efficacy for weight loss; however, its adverse reaction profile is varied in type and severity, with some events not explicitly listed in the prescribing information, underscoring the need for cautious clinical application.
