Effect of GLP-1 Receptor Agonism After Sleeve Gastrectomy

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebos; Drug: Saxenda; Procedure: RYGB

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age 20-65 years of age
2. Seen at Mayo Clinic Nutrition Clinic and have received authorization for bariatric surgery.
3. No active physical illness which will interfere with mobility or weight loss after bariatric surgery.
4. 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:

1. Prior use of glucose lowering medication in the 3 months prior to screening.
2. 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.
3. Prior abdominal surgery other than cholecystectomy, appendectomy or hysterectomy.
4. Pregnancy or active consideration of pregnancy during the period of study. Subjects will be discontinued if they become pregnant during the study.
5. Hypersensitivity to liraglutide or any product components.
6. Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2.
7. Prior history of pancreatitis, cholelithiasis or cholecystitis.
8. Concurrent use of insulin or any other GLP-1 receptor agonist.
9. Active, severe psychiatric disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sleeve Gastrectomy Placebo; Subjects undergoing Sleeve Gastrectomy (SG) will be randomized 1:1 at the time of 3 month visit after bariatric surgery.	Drug: Placebos; 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.; Other Names: Placebo for Saxenda (Liraglutide)
Active Comparator: Sleeve Gastrectomy Saxenda; Subjects undergoing Sleeve Gastrectomy (SG) will be randomized 1:1 at the time of 3 month visit after bariatric surgery.	Drug: Saxenda; 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.; Other Names: Liraglutide
Sham Comparator: RYGB; Twenty five subjects will be recruited from the Nutrition Clinic at Mayo Clinic Rochester prior to undergoing RYGB surgery.	Procedure: RYGB; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Subjects calculated weight in kilograms	baseline and 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure	Systolic blood pressure (top number of blood pressure reading)	baseline and 36 months
Diastolic Blood Pressure	Diastolic blood pressure (bottom number of blood pressure reading)	baseline and 36 months
Low-density Lipoprotein (LDL)	LDL's carry cholesterol through the bloodstream. LDL is called bad cholesterol because high amounts can form plaques in the blood vessels, increasing risk for heart disease. Adult normal range is less than 100 mg/dL.	baseline and 36 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Adrian Vella, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Actual): October 4, 2023
• Study Completion (Actual): May 30, 2024

Study Registration Dates

• First Submitted: April 5, 2017
• First Submitted That Met QC Criteria: April 11, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Weight Loss; Bariatric Surgery
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon-Like Peptide-1 Receptor Agonists; Liraglutide
• Other Study ID Numbers: 16-004253

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No