S781 Impact of Obesity Duration on Weight Loss Outcomes Following Endoscopic Sleeve Gastroplasty and GLP-1 Receptor Agonists

Introduction: It remains unclear whether patients with long-standing obesity respond similarly to weight loss interventions as those with more recent, rapid weight gain. We hypothesized that longer obesity duration may affect responsiveness to treatment. This study aimed to evaluate the impact of the chronicity of obesity on outcomes following 2 interventions: endoscopic sleeve gastroplasty (ESG) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Methods: Adults treated with ESG or GLP-1RAs (semaglutide or tirzepatide) from 2016 to 2024 were included. Long-term obesity (chronically obese) was defined as a stable body mass index (BMI) >30 kg/m² prior to Jan 2020. Recent obesity was defined as ≥7% weight gain since January 2020, and BMI ≥30 kg/m² within 3 years of treatment. Patients were categorized into 4 groups: chronic GLP-1 RA, recent GLP-1 RA, chronic ESG, and recent ESG. The primary outcome was total body weight loss (%TBWL) at 3, 6, and 12 months. Comparisons were conducted using t-tests and multivariate regression. Results: A total of 115 patients were included: chronic GLP-1 RA (n = 43), recent GLP-1 RA (n = 38), chronic ESG (n = 22), and recent ESG (n = 12). Mean age was 50 ± 12 years; 84% were women. Baseline characteristics were similar across groups. At 3 months, recent ESG group achieved significantly greater %TBWL than chronic ESG group (13% ± 5% vs 8% ± 3%, P < 0.05), a difference that persisted at 6 months (17% ± 6% vs 10% ± 4%, P < 0.05) but not at 12 months (19% ± 9% vs 17% ± 9%, P = 0.621). Among GLP-1 RA users, %TBWL did not differ significantly between recent and chronic groups at 3 months (5% ± 3% vs 6% ± 4%, P = 0.184), 6 months (9% ± 6% in both, P = 0.995), or 12 months (12% ± 7% vs 16% ± 10%, P = 0.230). ESG produced significantly greater weight loss than GLP-1 RA at 3 (10% ± 5% vs 6% ± 4%, P < 0.05) and 6 months (14% ± 7% vs 10% ± 6%, P < 0.05). By 12 months, the difference was no longer statistically significant (18% ± 9% vs 14% ± 8%, P = 0.121). Conclusion: Patients with recent-onset obesity achieved significantly greater weight loss at 3 and 6 months following ESG compared to those with long-standing obesity. However, by 12 months, outcomes were comparable. In contrast, GLP-1 RA effectiveness did not differ based on obesity duration. These findings suggest that prolonged exposure to obesity may impair the body's early response to endoscopic interventions. Larger studies are warranted to explore the pathophysiological mechanisms and to tailor treatment strategies based on obesity chronicity.