Weight Loss, Obesity
Conditions
Keywords
Weight Loss, Byetta (Exenatide), Energy Expenditure, Food Intake, Obesity
Brief summary
Exenatide is an incretin-like drug that has been approved for treatment of type 2 diabetes; it improves glycemia by increasing insulin and decreasing glucagon secretion by pancreatic islet cells and delaying gastric emptying. This randomized, placebo-controlled study is to evaluate whether exenatide over a 5 week period in non-diabetic obese subjects may lead to weight loss. To control for variability in individual response to weight loss treatment, this study will assess the role of exenatide in changing food intake and energy expenditure as possible sources of weight loss. This study will also evaluate the safety profile of exenatide in non-diabetic obese people. Additional assessments will evaluate changes in body fat and hormones involved in the sensations of hunger and fullness.
Detailed description
Obesity can lead to a number of health problems including diabetes, heart disease, stroke, low back pain, fatty liver disease, and osteoarthritis. The medical treatments currently available for obesity are limited. Exenatide is an injectable medication approved for treatment of type 2 diabetes that causes weight loss in some diabetic subjects. The reasons exenatide is thought to cause weight loss include decreased food intake, increased feelings of fullness and nausea. Because levels of a human gut hormone (glucagon like peptide 1) that is similar to exenatide have been shown to be related to resting energy expenditure, it is also possible that exenatide may have effects on a person s metabolism, a.k.a. energy expenditure, but any effect of exenatide on energy expenditure has yet to be evaluated. Even though exenatide is used to treat diabetes, administration of exenatide to non-diabetic lean individuals did not cause frankly low blood sugars. The primary goal of this study is to investigate the way in which exenatide given twice a day to obese (BMI \>= 30 kg/m\^2) people without diabetes might lead to weight loss. Because response to weight loss treatment can be highly variable between individuals, we will look at the role of exenatide in changing food intake and energy expenditure as possible explanations for weight loss. We will also assess the safety profile of exenatide in non-diabetic obese people. This study will involve the use of exenatide or placebo, determined randomly, in obese individuals without diabetes over a 5 week period. The primary measurements will include effects of exenatide on energy expenditure and food intake. We will also look at changes in body fat and the levels of hormones involved in the sensations of hunger and fullness. We will assess if any exenatide-induced changes can predict which individuals lose weight over the 5 weeks. The safety and side effects of exenatide in non-diabetic individuals during this time will also be determined. Findings from this study would help to determine how exenatide works to cause weight loss in people without diabetes, who might benefit most, and would help to improve understanding of why some people respond better to weight loss treatment than others.
Interventions
Exenatide is an injectable medication
BEHAVIORALWeight loss
Because response to weight loss
OTHERMetabolic Chamber
The subject stays in the small room
DRUGPlacebo
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: * Premenopausal women and men \< 55 years of age * BMI \>30 kg/m(2) * Expressed desire for weight loss * Stable weight (variation \< 2.3 kg within past 6 months) * Ability to provide informed consent * Ability to follow verbal and written instructions * Nonsmoker * Ability to commute to study site on a regular basis for short outpatient visits over 5 weeks * For females, use of a medically approved form of contraception. For oral contraceptives, subjects will need to be on an established dose for at least 3 months to ensure stable weight and will be asked not to switch contraceptive methods during study participation.
Exclusion criteria
* Age \< 18 years * Use of other medications to treat obesity including medications obtained over the counter or internet, orlistat (Xenical, Alli), sibutramine (Meridia), topiramate (with or without phentermine (Qsymia), phentermine (Adipex P) or lorcaserin (Belviq) within the past 6 months * History of an eating disorder including anorexia or bulimia * History of surgery for the treatment of obesity (gastric banding, gastric bypass) * Diagnosis of type 1 or type 2 diabetes mellitus according to American Diabetes Association guidelines * Previous exposure to exenatide * Uncontrolled hypertension as defined by a blood pressure of 150/90 on two or more occasions or use of antihypertensive medications which may affect energy expenditure including alpha blockers, beta blockers, angiotensin receptor blockers or inhibitors of angiotensin converting enzyme * Current use of tobacco products, marijuana, amphetamines, cocaine or intravenous drug use * Chronic ethanol use (\> 3 drinks /day) * Endocrine disorders including hypo or hyperthyroidism (including subclinical disease), Cushing s disease, growth hormone deficiency or other pituitary diseases * History of pancreatitis * Personal or family history of multiple endocrine neoplasia (MEN)-2 or medullary thyroid cancer * History of unresolved gallstones * Hyperamylasemia * Fasting triglyceride level greater than or equal to 500 * Gastroparesis * Inflammatory bowel disease or malabsorption disorders * Malignancy treated with chemotherapy or radiation within the past 5 years * Current clinical depression, diagnosis of psychosis or recent use of psychotropic medication * Pregnancy within past 6 months * Breastfeeding * Failure to use medically approved contraceptive methods if subject is female * Liver function abnormalities (transaminases greater than twice normal) * Renal insufficiency (creatinine clearance \< 50 ml/min) * History of chronic infection including tuberculosis, coccidiomycoses, lyme disease or HIV infection * Pulmonary disorders, including chronic obstructive pulmonary disease, which would limit ability to follow the protocol (investigator judgment) * Cardiovascular disease including history of myocardial infarction, unstable angina or heart failure * Central nervous system disease, including history of cerebrovascular accidents, dementia, and neurodegenerative disorders * Weight \<450 pounds (maximum weight of the DXA machine as per manufacturer s manual) * Sensitivity to exenatide or any inert components in its formulation * Sensitivity to acetaminophen * Conditions not specifically mentioned above may serve as criteria for exclusion at the discretion of the investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Energy Intake | Day 6-7-8 (at baseline) and Day 12-13-14 (3 days after starting study intervention) | Mean of 3-day food intake change between 3 days (Day 6-7-8) at baseline assessment and 3 days (Day 12-13-14) during the intervention period between the exenatide and placebo groups |
| Twenty-four-hour Energy Expenditure | Day 5 and Day 11 | Change of twenty-four-hour energy expenditure between at Day 5 at baseline assessment and at Day 11 two days after starting study medication between the exenatide and placebo groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight | 5 weeks | Mean decrease between pre- and post-randomization in 5 Weeks between the exenatide and placebo groups. |
Countries
United States
Participant flow
Pre-assignment details
Out of 150 planned total number of enrollment, 145 participants were recruited. Among the 145 participants, 84 participants met inclusion criteria. Only 80 participants out of 84 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide 10 micrograms subcutaneously twice
Byetta (exenatide): Exenatide is an injectable medication
Weight loss: Because response to weight loss | 40 |
| Placebo Twice daily
Metabolic Chamber: The subject stays in the small room
Placebo | 39 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Exenatide |
|---|---|---|---|
| 24 hour energy expenditure | 2333.8 kcal/day STANDARD_DEVIATION 422 | 2325.9 kcal/day STANDARD_DEVIATION 385.3 | 2319.3 kcal/day STANDARD_DEVIATION 377 |
| Age, Continuous | 33.7 years STANDARD_DEVIATION 9 | 34.4 years STANDARD_DEVIATION 8.7 | 35.1 years STANDARD_DEVIATION 8.4 |
| Awake fed thermogenesis | 671.0 kcal/day STANDARD_DEVIATION 232 | 648.7 kcal/day STANDARD_DEVIATION 203.2 | 629.9 kcal/day STANDARD_DEVIATION 176.3 |
| Body fat | 44.4 percent STANDARD_DEVIATION 8.7 | 44.2 percent STANDARD_DEVIATION 7.8 | 44.0 percent STANDARD_DEVIATION 6.9 |
| Body Mass Index | 38.2 kg/m^2 STANDARD_DEVIATION 6.8 | 38.1 kg/m^2 STANDARD_DEVIATION 6.7 | 38.0 kg/m^2 STANDARD_DEVIATION 6.6 |
| Body weight | 108.8 kg STANDARD_DEVIATION 20.7 | 107.1 kg STANDARD_DEVIATION 19.9 | 105.5 kg STANDARD_DEVIATION 19.2 |
| Carbohydrate oxidation | 1068.4 kcal/day STANDARD_DEVIATION 322.5 | 1097.0 kcal/day STANDARD_DEVIATION 338.3 | 1121.1 kcal/day STANDARD_DEVIATION 353.5 |
| Carbohydrates intake | 1593.8 kcal/day STANDARD_DEVIATION 476.1 | 1689.7 kcal/day STANDARD_DEVIATION 544 | 1785.5 kcal/day STANDARD_DEVIATION 595.5 |
| Fasting glucose | 98.8 mg/dl STANDARD_DEVIATION 8.8 | 97.8 mg/dl STANDARD_DEVIATION 8.6 | 96.9 mg/dl STANDARD_DEVIATION 8.5 |
| Fat free mass | 37.9 Kg STANDARD_DEVIATION 8.7 | 36.3 Kg STANDARD_DEVIATION 12.8 | 34.6 Kg STANDARD_DEVIATION 11.5 |
| Fat intake | 1130.9 kcal/day STANDARD_DEVIATION 484.6 | 1218.1 kcal/day STANDARD_DEVIATION 491.2 | 1305.3 kcal/day STANDARD_DEVIATION 488.4 |
| Fat mass | 30.8 Kg STANDARD_DEVIATION 8.7 | 29.4 Kg STANDARD_DEVIATION 8.8 | 27.9 Kg STANDARD_DEVIATION 8.8 |
| Lipid Oxidation | 873.5 kcal/day STANDARD_DEVIATION 377.6 | 823.3 kcal/day STANDARD_DEVIATION 353.1 | 781.0 kcal/day STANDARD_DEVIATION 330.2 |
| Mean energy intake | 3093.5 kcal/day STANDARD_DEVIATION 992.3 | 3294.5 kcal/day STANDARD_DEVIATION 1096.3 | 3495.5 kcal/day STANDARD_DEVIATION 1169.6 |
| Percentage of calories needed for weight maintenance participants consumed | 105.4 Percentage of Carlories STANDARD_DEVIATION 29.6 | 112.3 Percentage of Carlories STANDARD_DEVIATION 36.9 | 119.3 Percentage of Carlories STANDARD_DEVIATION 42.1 |
| Protein intake | 396.9 kcal/day STANDARD_DEVIATION 139.6 | 415.6 kcal/day STANDARD_DEVIATION 150.1 | 434.2 kcal/day STANDARD_DEVIATION 159.5 |
| Race/Ethnicity, Customized African American | 9 Participants | 10 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants | 10 Participants | 4 Participants |
| Race/Ethnicity, Customized Native American | 14 Participants | 36 Participants | 22 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 21 Participants | 11 Participants |
| Respiratory quotient | 0.85 ratio STANDARD_DEVIATION 0.03 | 0.86 ratio STANDARD_DEVIATION 0.03 | 0.86 ratio STANDARD_DEVIATION 0.03 |
| Sex: Female, Male Female | 23 Participants | 46 Participants | 23 Participants |
| Sex: Female, Male Male | 16 Participants | 33 Participants | 17 Participants |
| Sleeping metabolic rate | 1800.6 kcal/day STANDARD_DEVIATION 286.5 | 1810.1 kcal/day STANDARD_DEVIATION 279.7 | 1818.1 kcal/day STANDARD_DEVIATION 277.5 |
| Soda intake | 183.3 kcal/day STANDARD_DEVIATION 169.1 | 195.0 kcal/day STANDARD_DEVIATION 159.5 | 206.5 kcal/day STANDARD_DEVIATION 191.3 |
| Spontaneous physical activity | 79.4 kcal/day STANDARD_DEVIATION 43.4 | 80.0 kcal/day STANDARD_DEVIATION 45.1 | 80.4 kcal/day STANDARD_DEVIATION 47.1 |
| Two-hour glucose | 135.1 mg/dl STANDARD_DEVIATION 25.6 | 137.2 mg/dl STANDARD_DEVIATION 25.6 | 139.4 mg/dl STANDARD_DEVIATION 25.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 39 |
| other Total, other adverse events | 39 / 40 | 39 / 39 |
| serious Total, serious adverse events | 0 / 40 | 0 / 39 |
Outcome results
Primary
Energy Intake
Mean of 3-day food intake change between 3 days (Day 6-7-8) at baseline assessment and 3 days (Day 12-13-14) during the intervention period between the exenatide and placebo groups
Time frame: Day 6-7-8 (at baseline) and Day 12-13-14 (3 days after starting study intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Energy Intake | 1016.1 kcal/day | Standard Deviation 724.5 |
| Placebo | Energy Intake | 245.1 kcal/day | Standard Deviation 710.5 |
p-value: 0.0195% CI: [-901.8, -347.8]ANCOVA
Primary
Twenty-four-hour Energy Expenditure
Change of twenty-four-hour energy expenditure between at Day 5 at baseline assessment and at Day 11 two days after starting study medication between the exenatide and placebo groups
Time frame: Day 5 and Day 11
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Twenty-four-hour Energy Expenditure | 51.6 kcal/day | Standard Deviation 157.2 |
| Placebo | Twenty-four-hour Energy Expenditure | 28.9 kcal/day | Standard Deviation 119.7 |
p-value: 0.0195% CI: [-89.7, 41.4]ANCOVA
Secondary
Body Weight
Mean decrease between pre- and post-randomization in 5 Weeks between the exenatide and placebo groups.
Time frame: 5 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Body Weight | 1.6 kg | Standard Deviation 3.15 |
| Placebo | Body Weight | 0.27 kg | Standard Deviation 2.96 |
p-value: 0.0595% CI: [-3.02, 0.05]ANCOVA