MON-684 Comparative Effectiveness and Safety of GLP-1 Receptor Agonist versus Traditional Anti-obesity Medications: A Real-world Evidence Study

Abstract Disclosure: J. Chen: None. S. Chen: None. S. Yang: None. Y. Huang: None. P. Su: None. Background: While GLP-1 receptor agonists have shown promise in obesity treatment, their comparative safety and efficacy versus established medications remain unclear. Aims: We investigated whether semaglutide demonstrated superior cardiovascular and renal outcomes compared to Qsymia, phentermine, and Contrave in adults with obesity over two years. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network database (2015-2024). After excluding patients with diabetes, HIV, end-stage renal disease, and prior bariatric surgery, we matched 10,544 patients in each treatment group using propensity scores. To minimize selection bias, we balanced 42 baseline characteristics including demographics, comorbidities, and laboratory values. We assessed outcomes using Cox proportional hazards models with robust standard errors. Primary outcomes included all-cause mortality, cardiovascular events, and adverse events. Results: Semaglutide reduced all-cause mortality compared to Qsymia (HR 0.16, 95% CI 0.05-0.52), Contrave (HR 0.17, 95% CI 0.04-0.72), and phentermine (HR 0.28, 95% CI 0.12-0.68). Primary hypertension risk decreased with semaglutide versus all comparators (HRs ranging 0.69-0.84, all p<0.05). Semaglutide users experienced fewer strokes versus Qsymia (HR 0.40, 95% CI 0.19-0.85) and showed improved chronic kidney disease outcomes (HR 0.56, 95% CI 0.32-0.97). However, gastrointestinal events were more frequent with semaglutide, particularly vomiting (HRs 1.28-1.50 versus comparators) and constipation. Sensitivity analyses stratified by age, sex, and race showed consistent results across subgroups. Conclusions: In this large real-world study, semaglutide demonstrated superior cardiovascular and renal protection compared to other obesity medications, despite increased gastrointestinal side effects. These findings suggest the need for individualized benefit-risk assessment when selecting obesity pharmacotherapy. Future randomized trials should validate these observational findings. Presentation: Monday, July 14, 2025