S798 Endoscopic Sleeve Gastroplasty vs GLP-1 Receptor Agonists: Comparative Effectiveness in Obesity Management

Introduction: Endoscopic sleeve gastroplasty (ESG) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are 2 leading non-surgical interventions for obesity. While both are widely used, real-world comparative data on their effectiveness and safety remain limited. This study evaluated clinical outcomes associated with ESG versus GLP-1 RAs using a large, multicenter health record network. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, identifying adults aged ≥18 years with body mass index (BMI) ≥30 kg/m² who underwent either ESG or initiated GLP-1 RA therapy between 2015 and 2025. Patients with overlapping exposures were excluded to ensure mutually exclusive groups. Propensity score matching (1:1) was performed based on demographics and comorbidities. The primary outcome was obesity improvement, defined by reductions in weight and BMI. Secondary outcomes included changes in obesity-related metabolic conditions (obstructive sleep apnea [OSA], hyperlipidemia, non-alcoholic fatty liver disease [NAFLD]) and adverse events (nutritional deficiencies, cholecystitis, pancreatitis, hypoglycemia). Kaplan-Meier analysis and hazard ratios (HRs) were used to compare outcomes. Results: After propensity matching, 550 patients were included in each cohort. ESG was associated with significantly greater odds of obesity improvement compared to GLP-1 RAs (hazard ratio [HR] 1.58; 95% confidence interval [CI]: 1.37–1.83; P < 0.001). However, ESG patients experienced a higher risk of nutritional deficiencies (HR 2.30; 95% CI: 1.51–3.50) and cholecystitis (HR 1.58; 95% CI: 0.58–4.29; P = 0.047). In contrast, patients on GLP-1 RAs had a higher persistence of hyperlipidemia (HR 0.78; 95% CI: 0.63–0.97; P = 0.028). There were no significant differences between groups in rates of pancreatitis, hypoglycemia, NAFLD, or mental health outcomes. Conclusion: In this large, matched real-world cohort, ESG provided superior weight loss benefits compared to GLP-1 RA therapy but carried an increased risk of nutritional and gallbladder-related complications. Conversely, GLP-1 RAs offered a more favorable metabolic safety profile with slightly lower weight loss efficacy. These findings highlight the critical need for individualized, patient-centered obesity care. As non-surgical strategies evolve, clinicians must weigh the anatomical durability of ESG against the systemic metabolic modulation of GLP-1 therapy—aligning treatment with patient preferences, risk tolerance, and long-term health goals.