A 10‐Year Nationwide Pharmacovigilance Assessment on Anti‐Obesity Medications and Factors Associated with Serious Adverse Events

Abstract

Study ObjectiveTo compare the adverse events (AEs) profiles of medications prescribed to treat obesity and identify factors associated with serious adverse events (SAEs) by utilizing nationwide spontaneous AE reporting database in Korea.HypothesisThe AE profiles may differ by anti‐obesity agents and patient‐specific factors may aggravate the risk of SAEs.MethodsRetrospective analysis was performed on ADE records spontaneously reported from January 2010 to December 2019 to the Korean Adverse Event Reporting System (KAERS) constructed by Korea Institute of Drug Safety and Risk Management. This analysis included 10 anti‐obesity agents prescribed for overweight, obesity (ICD‐10 code E66) and abnormal weight gain (ICD10 Code E63.5). All AEs were grouped using preferred terms and System Oran Classes (SOC) per the WHO‐Adverse Reaction Terminology. Logistic regression was performed to identify factors associated with SAEs identified based on International Conference on Harmonization E2D Guidelines, and the odds ratio (OR) was reported with 95% confidence intervals (CIs). Any p‐values <0.05 was considered statistically significant. All statistical analyses were performed with SPSS 25.0 (Version 25.0; IBM SPSS Statistics for Windows, Armonk, NY, USA). The study protocol for utilizing the KAERS database was approved by KIDS (No.2007A0051) and the institutional review board of CHA University (Pocheon, South Korea).ResultsTotal of 4,215 AE records associated with anti‐obesity agents were identified, and the most etiologic anti‐obesity agent was phentermine (n=1,385; 32.8%), followed by liraglutide (n=1,155; 27.4%) and lorcaserin (n=690; 16.3%). AEs were frequently reported in females (n=3,458; 88.7%) and patients in their 30s (n=761; 18.1%) or 40s (n=672; 15.9%) of age. The prevalence of SAE was 2.5% (n=105). The highest number of nonserious AEs was gastro‐intestinal system disorders (n=1,233; 30.0%), followed by central & peripheral nervous system disorders (n=782; 19.0%) and psychiatric disorders (n=682; 16.6%). The most common SAEs were associated with psychiatric disorders (n=27; 25.7%), central & peripheral nervous system disorders (n=20; 19.0%), and gastrointestinal system disorders (n=13; 12.4%). The reporting odds ratio of SAE in liver and biliary system disorders from anti‐obesity agent administration was 3.145 (95% CI 6.689‐ 80.557). Factors associated with significantly elevated risk of SAEs was male sex (odds ratio (OR) 6.318; 95% CI 3.583‐10.839), triple agent therapy (OR 3.49; 95% CI:1.481‐8.170), increasing number of medications (OR 1.381; 95% CI 1.204‐1.583), and concomitant administration of fluoxetine (OR 5.146; 95% CI 2.570‐10.268).ConclusionThis is the first study of the study investigating AEs induced by medications primarily prescribed for weight loss by utilizing nationwide spontaneous adverse event reporting system. AEs induced by anti‐obesity agents are most frequently reported with phentermine and liraglutides, primarily manifested by gastrointestinal system disorders. SAEs are substantially associated with male gender, polypharmacy, and type of concomitant medications.