Effect of GLP-1 Receptor Agonism After Sleeve Gastrectomy

Study Overview
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Brief Summary
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Observational studies suggest that bariatric surgery is the most effective intervention for weight loss. Comparative effectiveness of Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) demonstrate that RYGB is significantly superior to SG in terms of weight loss and glycemic control. Both RYGB and SG increase GLP-1 concentrations which directly affect B-cell function. Data has shown that the postprandial rise in GLP-1 might affect feeding behavior after RYGB and to a lesser extent SG, where the increase in GLP-1 is less marked. In this study the investigators propose to randomize subjects undergoing SG to receive either placebo or Liraglutide, a GLP-1 receptor agonist, to compare weight loss and CV risk factors.

Detailed Description
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A total of 75, non diabetic adults, scheduled for bariatric surgery at Mayo Clinic Rochester, will be enrolled. Of these, 25 will be scheduled for Roux-en-Y Gastric Bypass surgery (RYGB), while the remainder (50) will be scheduled for Sleeve Gastrectomy (SG). The study team will play no role in assignment of the surgical procedure. Following surgery, at month 3, subjects undergoing SG will be randomized to either Saxenda or placebo, subcutaneously once daily. Subjects randomized to Saxenda or placebo will take for the duration of the study (33 months). Follow up study visits for all subjects will be timed to coincide with the standard clinical follow up visits at months 3, 6, 9, 12, 18, 24, 30 and 36.

Official Title
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Effect of GLP-1 Receptor Agonism on Weight and Caloric Intake in Subjects After Sleeve Gastrectomy

Conditions
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Obesity

Intervention / Treatment
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* Drug: Saxenda
* Drug: Placebos
* Procedure: RYGB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-65 years of age Seen at Mayo Clinic Nutrition Clinic and have received authorization for bariatric surgery. No active physical illness which will interfere with mobility or weight loss after bariatric surgery. Females who are sexually active and able to become pregnant must agree to use birth control for duration of study if randomized to Saxenda/Placebo. Exclusion Criteria: Prior use of glucose lowering medication in the 3 months prior to screening. A fasting glucose ≥ 126mg/dl or an HbA1c ≥ 6.5% will be taken as evidence of type 2 diabetes and therefore patients will be deemed ineligible for participation. Prior abdominal surgery other than cholecystectomy, appendectomy or hysterectomy. Pregnancy or active consideration of pregnancy during the period of study. Subjects will be discontinued if they become pregnant during the study. Hypersensitivity to liraglutide or any product components. Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2. Prior history of pancreatitis, cholelithiasis or cholecystitis. Concurrent use of insulin or any other GLP-1 receptor agonist. Active, severe psychiatric disease

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sleeve Gastrectomy Placebo<br>Subjects undergoing Sleeve Gastrectomy (SG) will be randomized 1:1 at the time of 3 month visit after bariatric surgery. | Drug: Placebos<br>* Subjects will be recruited and screened prior to undergoing bariatric surgery.Subjects undergoing SG will be randomized 1:1 at months 3 post surgery to Placebo, 0.6mg SQ daily, with weekly titration of 0.6mg until maintenance dose of 3mg/daily reached. Subjects will remain on study drug for duration of study (33 months). After undergoing surgery, study visits will be timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36.<br>* Other names: Placebo for Saxenda (Liraglutide);|
| Active Comparator: Sleeve Gastrectomy Saxenda<br>Subjects undergoing Sleeve Gastrectomy (SG) will be randomized 1:1 at the time of 3 month visit after bariatric surgery. | Drug: Saxenda<br>* Saxenda is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adult patients. Subjects will be recruited and screened prior to undergoing bariatric surgery. Subjects undergoing SG will be randomized 1:1 at month 3 post surgery to Saxenda, 0.6mg SQ daily, with weekly titration of 0.6mg until maintenance dose of 3mg/daily reached. Subjects will remain on study drug for duration of study (33 months). After undergoing surgery, study visits will be timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36.<br>* Other names: Liraglutide;|
| Sham Comparator: RYGB<br>Twenty five subjects will be recruited from the Nutrition Clinic at Mayo Clinic Rochester prior to undergoing RYGB surgery. | Procedure: RYGB<br>* Subjects will be recruited and screened prior to undergoing bariatric surgery. After undergoing surgery, study visits will be timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agonism of the GLP-1 receptor will Increase weight loss | Liraglutide administration (3mg daily) to participants after SG | 33 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agonism of the GLP-1 receptor will lower blood pressure. | Liraglutide administration (3mg daily) to participants after SG | 33 months | 
| Agonism of the GLP-1 receptor will lower LDL-cholesterol | Liraglutide administration (3mg daily) to participants after SG | 33 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight Loss, Bariatric Surgery