Endoscopic Sleeve Gastroplasty Versus Oral Semaglutide for Obesity: A Real-World Comparative Cohort Study.

BACKGROUND: Endoscopic sleeve gastroplasty (ESG) and semaglutide are established therapies for obesity. However, comparative real-world data remain limited. We compared the effectiveness and safety of ESG versus oral semaglutide 14 mg in adults with obesity. METHODS: In a real-world retrospective comparative cohort study between January 2024 and April 2025, adults aged 18-65 years with body mass index (BMI) ≥30, or ≥27 kg/m with obesity-related comorbidity, treated with either ESG or oral semaglutide 14mg daily, and having 6-months' follow-up were included. Primary endpoint was percentage total body weight loss (%TBWL) at 6 months. Secondary outcomes included treatment responder rates, adverse events, and 12-month weight outcomes. Analyses included Welch's two-sample -tests, analysis of covariance adjusted for age, sex, baseline BMI, and diabetes, inverse probability of treatment weighting (IPTW), and 1:1 propensity score matching. RESULTS: 150 patients were included (ESG n=50; semaglutide n=100). Baseline characteristics were broadly similar between groups. At 6 months, mean %TBWL was significantly higher with ESG than semaglutide (12.72±5.67% vs 8.67±3.84%, =0.0001) that remained after covariate adjustment (adjusted mean difference 4.04%, =0.0001), IPTW analysis (<0.001), and propensity-matched analysis (=0.021). Responder rates ≥10%TBWL were achieved in 70% with ESG versus 43% with semaglutide (relative risk [RR] 0.62, 95%CI 0.46-0.82, =0.0009), and ≥15%TBWL in 36% versus 7% (RR 0.20, 95%CI 0.09-0.44, =0.0006). There were no major adverse events. At 12 months, mean %TBWL was 11.92±6.93 with ESG and 10.91±4.66 with semaglutide (=0.41). During follow-up, 18 patients discontinued semaglutide and 5 ESG patients initiated semaglutide. CONCLUSIONS: ESG was associated with greater short-term weight loss and higher responder rates than oral semaglutide 14mg. At 12 months, weight loss was sustained in both groups without significant between-group difference. These preliminary findings should be interpreted with caution in absence of randomized trial design.