GLP-1 Therapy After Bariatric Surgery in Chinese Patients With Obesity

Official title

The Efficacy and Safety of Adjuvant GLP-1 Receptor Agonist Therapy Following Metabolic Bariatric Surgery in Chinese Patients With Obesity: A Prospective, Monocentric, Stratified Randomized Controlled Trial

Overview

Obese patients exhibit considerable heterogeneity and complex comorbidities, making long-term effective management challenging with monotherapy. While bariatric surgery remains the most effective weight-loss intervention, postoperative weight regain and metabolic deterioration remain significant concerns. glucagon-like peptide-1 receptor agonists (GLP-1RA) offer distinct advantages for weight loss and metabolic control, and their combination with surgery may produce synergistic effects. This study investigates the efficacy and safety of bariatric surgery combined with adjuvant GLP-1 receptor agonist therapy for Chinese patients with obesity.

Detailed description

Bariatric surgery is guideline-recommended as an effective obesity treatment. Substantial evidence demonstrates its ability to significantly reduce weight, improve comorbidities like type 2 diabetes (T2DM) and dyslipidemia, and lower cardiovascular risk. However, the significant heterogeneity and complex comorbidity profiles among obese patients challenge long-term effective management with single therapeutic approaches. While currently the most effective weight-loss intervention, bariatric surgery requires attention to issues such as postoperative weight regain and metabolic deterioration.

In parallel, glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated significant efficacy in obesity management. Agents like Semaglutide promote weight loss and metabolic improvement through mechanisms including insulin secretion promotion, appetite suppression, delayed gastric emptying, and enhanced satiety. Tirzepatide, as the first approved GLP-1/GIP dual-target agonist, demonstrates superior hypoglycemic and weight loss effects compared to Semaglutide through its synergistic interaction with GLP-1. Mazdutide, the first GLP-1/GCG dual-target agonist to enter phase III clinical trials in China, promotes fatty acid oxidation and energy consumption while acting synergistically with GLP-1's appetite-suppressing effect. It can effectively reduce liver fat content while achieving weight loss.

Given the distinct advantages of both bariatric surgery and GLP-1RA therapy in weight and metabolic control, this study will combine these modalities into a comprehensive treatment strategy. We will compare the long-term safety and effectiveness of different combination regimens for weight management and metabolic improvement in Chinese patients with obesity.

Interventions

• Combination product LSG-Semaglutide group
  1. Basic Treatment Measures Within 0-30 days after sleeve gastrectomy, all patients received very low-calorie enteral nutrition powder (100 kcal/day). From 30 to 90 days post-surgery, a low-energy diet (400 kcal/day) was provided. Beyond 90 days post-surgery, a calorie-restricted diet was implemented (1,500 kcal/day for men and 1,200 kcal/day for women). 2. In addition to laparoscopic sleeve gastrectomy and postoperative basic nutritional counseling,the LSG-Semaglutide group received subcutaneou
• Combination product LSG-Mazdutide group
  1. Basic Treatment Measures Within 0-30 days after sleeve gastrectomy, all patients received very low-calorie enteral nutrition powder (100 kcal/day). From 30 to 90 days post-surgery, a low-energy diet (400 kcal/day) was provided. Beyond 90 days post-surgery, a calorie-restricted diet was implemented (1,500 kcal/day for men and 1,200 kcal/day for women). 2. In addition to laparoscopic sleeve gastrectomy and postoperative basic nutritional counseling,the LSG-Mazdutide group received subcutaneous
• Combination product LSG-Tirzepatide group
  1. Basic Treatment Measures Within 0-30 days after sleeve gastrectomy, all patients received very low-calorie enteral nutrition powder (100 kcal/day). From 30 to 90 days post-surgery, a low-energy diet (400 kcal/day) was provided. Beyond 90 days post-surgery, a calorie-restricted diet was implemented (1,500 kcal/day for men and 1,200 kcal/day for women). 2. In addition to laparoscopic sleeve gastrectomy and postoperative basic nutritional counseling,the LSG-Tirzepatide group received subcutaneou
• Procedure LSG group
  1. Basic Treatment Measures Within 0-30 days after sleeve gastrectomy, all patients received very low-calorie enteral nutrition powder (100 kcal/day). From 30 to 90 days post-surgery, a low-energy diet (400 kcal/day) was provided. Beyond 90 days post-surgery, a calorie-restricted diet was implemented (1,500 kcal/day for men and 1,200 kcal/day for women). 2. Observation Group: Received only basic nutritional recommendation interventions after surgery.

Primary outcome measures

• Percentage of weight loss. [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]

Secondary outcome measures (12)

• Weight in kilograms [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Waist circumference in centimeters [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Hip circumference in centimeters [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Blood pressure [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Serum creatinine [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Glomerular filtration rate [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Fasting blood glucose [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Average blood glucose from continuous glucose monitoring [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Postprandial 2-hour blood glucose [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• HbA1c [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Urinary microalbumin [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Total cholesterol [Time frame: Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]

Eligibility criteria

Inclusion criteria

• Patients undergoing initial laparoscopic sleeve gastrectomy (LSG).
• obesity:BMI ≥30 kg/m².
• Metabolic comorbidities: Diagnosis of metabolic syndrome or type 2 diabetes mellitus (T2DM) meeting standard criteria.
• Age range: 18-60 years (inclusive).
• Informed consent: Willing participation with documented consent.

Exclusion criteria

• Recent GLP-1RA use: Treatment with GLP-1 receptor agonists within 6 months preoperatively.
• Prior bariatric surgery: History of any metabolic/bariatric surgical procedure.
• Postoperative complications: Requiring reoperation for severe complications (e.g., hemorrhage, anastomotic leak).
• Non-indicated candidates: Patients not meeting standard bariatric surgery indications.
• Significant comorbidities:

5.1Advanced hepatic/renal dysfunction (Child-Pugh C or eGFR <30 mL/min/1.73m²). 5.2Active malignancy (except non-melanoma skin cancers). 5.3Autoimmune disorders requiring immunosuppression. 5.4Uncontrolled psychiatric conditions (e.g., active psychosis, severe depression).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• China-Japan Friendship Hospital — Beijing

Identifiers

NCT: NCT07633639 · 2026-CJH-OBE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗