IBCOx-12 The Endoscopic Sleeve Gastroplasty Produces Durable Physiologic Changes: Results from a Randomized US Clinical Trial

Abstract

Abstract Background Obesity is associated with faster gastric emptying and altered appetite. Endoscopic sleeve gastroplasty (ESG) has gained global adaptation, but our understanding of its physiologic mechanism of action and durability is limited. We sought to determine changes in gastric emptying, weight loss, and eating behaviors after ESG when compared to moderate-intensity lifestyle interventions (LS) in the short and long-term. Methods This is an a priori designed sub-study of a large ongoing multicenter US RCT (MERIT trial), where adults with BMI 30-40 kg/m2 were randomized to ESG versus moderate-intensity LS alone. We measured gastric emptying (T1/2) using a 4- hour gastric emptying breath test at baseline, 3 and 12 months into the study. We reported weight loss outcomes as percent total body weight lost (%TBWL). Changes in three eating behaviour domains (Cognitive Restraint [CR], Emotional Eating [EE], Uncontrolled Eating [UE]) were assessed using the Three-Factor Eating Questionnaire (TFEQ) at 6 months. The primary outcome was the change in T1/2 (minutes) at 3 months, and secondary outcomes were changes in T1/2 at 12 months, %TBWL, and eating behaviours. We used the t-test for the analyses. Linear regression was performed to determine the association between gastric emptying and weight loss. Results 46 patients were randomized in the study (ESG n=26; LS n=20). Baseline characteristics were similar between the two groups. Out of n=46, n=43, and n=31 subjects have reached 3 and 12 months, respectively. Three patients dropped out of the study. At 3 months, T1/2 (minutes) was delayed in the ESG group (n=24) compared to the LS group (n=19) (170.8 vs. 87.5; p<0.0001). At 12 months, T1/2 was still delayed in the ESG group (n=17) vs. control group (n=14) (133.4 vs. 87.6; p=0.0005), and delayed compared to baseline. %TBWL in the ESG group was 12.3%, 15.1% and 15.7% at 3, 6 and 12 months (p <0.01 compared to baseline), while it was 2.3%, 2.2% and 0.3% (p>0.05 compared to baseline) in the LS group. Greater delays in gastric emptying at 3 months correlated with weight loss at all time points. (Figure 1) At 6 months, significant improvements in the EE and UE domains were seen in both groups, but for CR, only significant improvements were seen in the ESG group. Percent total fasting ghrelin, GLP-1, and PYY increased at 12 months in the ESG group compared to LS control (51%, 51%, 6.3% vs. -9%, 4%, -10.5%). Only 1 SAE managed endoscopically with full recovery was reported in the ESG group. Conclusions ESG produces sustained physiologic alterations in appetite regulatory pathways and durable weight-loss. This provides further evidence supporting the clinical adoption of the technique as a durable and effective obesity therapy.