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

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.

• LSG-Semaglutide group (Combination product): 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 subcutaneous semaglutide injections from 1 to 6 months postoperatively.The specific protocol was as follows:In the intervention group, semaglutide treatment was initiated at 1 month after LSG. The starting dose was 0.25 mg per week and was subsequently titrated up based on individual patient response to a maximum maintenance dose of 2.4 mg per week. The treatment continued until the completion of the 6-month postoperative period.
• LSG-Mazdutide group (Combination product): 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 Mazdutide injections from 1 to 6 months postoperatively.The specific protocol was as follows:In the intervention group, Mazdutide treatment was initiated at 1 month after LSG. The starting dose was 2 mg per week and was subsequently titrated up based on individual patient response to a maximum maintenance dose of 6 mg per week. The treatment continued until the completion of the 6-month postoperative period.
• LSG-Tirzepatide group (Combination product): 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 subcutaneous Tirzepatide injections from 1 to 6 months postoperatively.The specific protocol was as follows:In the intervention group, Tirzepatide treatment was initiated at 1 month after LSG. The starting dose was 2.5 mg per week and was subsequently titrated up based on individual patient response to a maximum maintenance dose of 10 mg per week. The treatment continued until the completion of the 6-month postoperative period.
• LSG group (Procedure): 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 outcomes

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

Secondary outcomes

• Weight in kilograms [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Waist circumference in centimeters [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Hip circumference in centimeters [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Blood pressure [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Serum creatinine [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Glomerular filtration rate [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Fasting blood glucose [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Average blood glucose from continuous glucose monitoring [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Postprandial 2-hour blood glucose [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• HbA1c [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Urinary microalbumin [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Total cholesterol [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Low-Density Lipoprotein(LDL) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Triglycerides [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Alanine Aminotransferase(ALT) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Aspartate Aminotransferase(AST) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• urine microalbumin-to-creatinine ratio (ACR) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• uric acid(UA) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• body fat percentage(BFP) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Visceral fat area [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Muscle mass in kilograms [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Body fat percentage [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• lean body mass (LBM) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• lean body mass percentage (LBMP) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Liver Stiffness Measurement(LSM) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]
• Controlled Attenuation Parameter(CAP) [Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively.]

Sex: All, ages: 18 Years to 60 Years

Inclusion Criteria:

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

Exclusion Criteria:

1. Recent GLP-1RA use: Treatment with GLP-1 receptor agonists within 6 months preoperatively.
2. Prior bariatric surgery: History of any metabolic/bariatric surgical procedure.
3. Postoperative complications: Requiring reoperation for severe complications (e.g., hemorrhage, anastomotic leak).
4. Non-indicated candidates: Patients not meeting standard bariatric surgery indications.
5. 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).