Obesity
Conditions
Keywords
Weight Loss, Bariatric Surgery
Brief summary
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
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.
Interventions
DRUGSaxenda
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.
DRUGPlacebos
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.
PROCEDURERYGB
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.
Sponsors
Novo Nordisk A/S
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind design.
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight | baseline and 36 months | Subjects calculated weight in kilograms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | baseline and 36 months | Systolic blood pressure (top number of blood pressure reading) |
| Diastolic Blood Pressure | baseline and 36 months | Diastolic blood pressure (bottom number of blood pressure reading) |
| Low-density Lipoprotein (LDL) | baseline and 36 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sleeve Gastrectomy Saxenda Subjects underwent Sleeve Gastrectomy (SG) were randomized 1:1 at the time of 3 month visit after bariatric surgery.
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 were recruited and screened prior to undergoing bariatric surgery. Subjects undergoing SG will were 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. After undergoing surgery, study visits were timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36. | 12 |
| Sleeve Gastrectomy Placebo Subjects underwent Sleeve Gastrectomy (SG) were randomized 1:1 at the time of 3 month visit after bariatric surgery.
Placebos: Subjects were recruited and screened prior to undergoing bariatric surgery. Subjects undergoing SG were 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 remained on study drug for duration of study. After undergoing surgery, study visits were timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36. | 9 |
| Roux-en-Y Gastric (RYGB) Subjects were recruited from the Nutrition Clinic at Mayo Clinic Rochester prior to undergoing RYGB surgery.
RYGB: Subjects were recruited and screened prior to undergoing bariatric surgery. After undergoing surgery, study visits were timed to coincide with the standard clinical follow-up visits at months 3, 6, 9, 12, 18, 24, 30 and 36. | 25 |
| Total | 46 |
Baseline characteristics
| Characteristic | Sleeve Gastrectomy Placebo | Roux-en-Y Gastric (RYGB) | Total | Sleeve Gastrectomy Saxenda |
|---|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 11 | 42 years STANDARD_DEVIATION 9 | 43 years STANDARD_DEVIATION 10 | 46 years STANDARD_DEVIATION 12 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United States | 9 participants | 25 participants | 46 participants | 12 participants |
| Sex: Female, Male Female | 8 Participants | 22 Participants | 40 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 9 | 0 / 25 |
| other Total, other adverse events | 2 / 12 | 1 / 9 | 14 / 25 |
| serious Total, serious adverse events | 1 / 12 | 0 / 9 | 0 / 25 |
Outcome results
Primary
Weight
Subjects calculated weight in kilograms
Time frame: baseline and 36 months
Population: Data was not collected nor analyzed for eight subjects in the Sleeve Gastrectomy Saxenda arm. Data was not collected nor analyzed for seven subjects in the Sleeve Gastrectomy Placebo arm. Data was not collected nor analyzed for thirteen subjects in the Roux-en-Y Gastric (RYGB).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sleeve Gastrectomy Saxenda | Weight | baseline | 127 kilograms | Standard Error 7 |
| Sleeve Gastrectomy Saxenda | Weight | 36 months | 75 kilograms | Standard Error 8 |
| Sleeve Gastrectomy Placebo | Weight | baseline | 130 kilograms | Standard Error 8 |
| Sleeve Gastrectomy Placebo | Weight | 36 months | 107 kilograms | Standard Error 10 |
| Roux-en-Y Gastric (RYGB) | Weight | baseline | 126 kilograms | Standard Error 4 |
| Roux-en-Y Gastric (RYGB) | Weight | 36 months | 98 kilograms | Standard Error 7 |
Secondary
Diastolic Blood Pressure
Diastolic blood pressure (bottom number of blood pressure reading)
Time frame: baseline and 36 months
Population: Data was not collected nor analyzed for eight subjects in the Sleeve Gastrectomy Saxenda arm. Data was not collected nor analyzed for seven subjects in the Sleeve Gastrectomy Placebo arm. Data was not collected nor analyzed for thirteen subjects in the Roux-en-Y Gastric (RYGB).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sleeve Gastrectomy Saxenda | Diastolic Blood Pressure | baseline | 86 Millimeters of Mercury | Standard Error 3 |
| Sleeve Gastrectomy Saxenda | Diastolic Blood Pressure | 36 months | 84 Millimeters of Mercury | Standard Error 4 |
| Sleeve Gastrectomy Placebo | Diastolic Blood Pressure | baseline | 83 Millimeters of Mercury | Standard Error 6 |
| Sleeve Gastrectomy Placebo | Diastolic Blood Pressure | 36 months | 93 Millimeters of Mercury | Standard Error 13 |
| Roux-en-Y Gastric (RYGB) | Diastolic Blood Pressure | baseline | 76 Millimeters of Mercury | Standard Error 2 |
| Roux-en-Y Gastric (RYGB) | Diastolic Blood Pressure | 36 months | 82 Millimeters of Mercury | Standard Error 3 |
Secondary
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.
Time frame: baseline and 36 months
Population: Data was not collected nor analyzed for eight subjects in the Sleeve Gastrectomy Saxenda arm. Data was not collected nor analyzed for seven subjects in the Sleeve Gastrectomy Placebo arm. Data was not collected nor analyzed for thirteen subjects in the Roux-en-Y Gastric (RYGB).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sleeve Gastrectomy Saxenda | Low-density Lipoprotein (LDL) | baseline | 114 mg/dL | Standard Error 9 |
| Sleeve Gastrectomy Saxenda | Low-density Lipoprotein (LDL) | 36 months | 106 mg/dL | Standard Error 20 |
| Sleeve Gastrectomy Placebo | Low-density Lipoprotein (LDL) | baseline | 101 mg/dL | Standard Error 11 |
| Sleeve Gastrectomy Placebo | Low-density Lipoprotein (LDL) | 36 months | 68 mg/dL | Standard Error 1 |
| Roux-en-Y Gastric (RYGB) | Low-density Lipoprotein (LDL) | baseline | 99 mg/dL | Standard Error 5 |
| Roux-en-Y Gastric (RYGB) | Low-density Lipoprotein (LDL) | 36 months | 90 mg/dL | Standard Error 7 |
Secondary
Systolic Blood Pressure
Systolic blood pressure (top number of blood pressure reading)
Time frame: baseline and 36 months
Population: Data was not collected nor analyzed for eight subjects in the Sleeve Gastrectomy Saxenda arm. Data was not collected nor analyzed for seven subjects in the Sleeve Gastrectomy Placebo arm. Data was not collected nor analyzed for thirteen subjects in the Roux-en-Y Gastric (RYGB).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sleeve Gastrectomy Saxenda | Systolic Blood Pressure | baseline | 129 Millimeters of Mercury | Standard Error 4 |
| Sleeve Gastrectomy Saxenda | Systolic Blood Pressure | 36 months | 112 Millimeters of Mercury | Standard Error 7 |
| Sleeve Gastrectomy Placebo | Systolic Blood Pressure | baseline | 130 Millimeters of Mercury | Standard Error 7 |
| Sleeve Gastrectomy Placebo | Systolic Blood Pressure | 36 months | 128 Millimeters of Mercury | Standard Error 1 |
| Roux-en-Y Gastric (RYGB) | Systolic Blood Pressure | baseline | 123 Millimeters of Mercury | Standard Error 4 |
| Roux-en-Y Gastric (RYGB) | Systolic Blood Pressure | 36 months | 122 Millimeters of Mercury | Standard Error 7 |