ERCG vs Intensive Lifestyle Intervention for Weight Regain After GLP-1 RA Discontinuation

Obesity is a chronic condition in which weight regain may occur after successful weight loss. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for weight management, but some individuals regain weight after treatment is discontinued. Effective treatment strategies for weight regain following GLP-1 RA discontinuation remain limited.

ERCG is a novel endoscopic procedure that reduces gastric volume by apposing the gastric walls using a newly designed clip-and-loop system. Preliminary studies suggest that ERCG may produce clinically meaningful weight loss, but its efficacy and safety specifically in people who have regained weight after GLP-1 RA withdrawal require prospective evaluation.

This is a two-arm, parallel-group, open-label randomized clinical trial. Approximately 60 eligible participants will be randomly assigned in a 1:1 ratio to the ERCG plus ILI or ILI alone. Randomization will be computer-generated, with allocation concealed until assignment. Participants assigned to the ERCG group will undergo ERCG under general anesthesia or deep sedation according to a standardized perioperative protocol.

Both groups will receive the same ILI program from randomization through week 52. The program will include individualized dietary counseling aimed at an approximately 500-750 kcal/day energy deficit when clinically appropriate; a gradual increase in physical activity toward at least 150 minutes per week of moderate-intensity activity, tailored to individual capacity; and behavioral support focused on goal setting, self-monitoring, problem solving, and relapse prevention. Trained study staff will deliver the program using a common intervention manual, with weekly contacts during weeks 1-12, contacts every two weeks during weeks 13-24, and monthly contacts during weeks 25-52. Dietary intake, physical activity, body weight, and attendance will be recorded to assess adherence. Participants in the ERCG group will additionally follow a standardized postoperative diet advancement protocol before progressing to the same dietary goals as the ILI-only group.

The primary outcome is %TBWL at week 12, calculated as (body weight at randomization - body weight at week 12) / body weight at randomization × 100%. The primary comparison will assess the difference in %TBWL between groups. Secondary outcomes include %TBWL at weeks 24 and 52; changes in BMI, body composition, fasting plasma glucose, HbA1c, insulin resistance indices, lipid profile, and quality of life measured with a validated questionnaire; and adherence to the assigned interventions. Body weight will be measured using a standardized protocol at baseline and scheduled follow-up visits.

Safety will be assessed in both groups throughout the 52-week follow-up. For participants undergoing ERCG, investigators will document technical completion, procedure and anesthesia-related events, and early and delayed complications, including bleeding, perforation, infection, persistent abdominal pain, nausea or vomiting, impaired oral intake, and events related to the clip-and-loop system. Safety assessments will include perioperative observation, early postoperative contacts, and evaluations at scheduled follow-up visits. All adverse events will be recorded with their onset, duration, severity, management, outcome, and assessed relationship to ERCG or study interventions. Endoscopy-related adverse events will be classified using the American Society for Gastrointestinal Endoscopy (ASGE) lexicon; serious adverse events and unplanned hospitalizations or reinterventions will be reported according to the study protocol.

Outcome assessors will be blinded to group assignment where feasible. The primary analysis will follow the intention-to-treat principle, with prespecified methods for handling missing outcome data.