Obesity, Overweight
Conditions
Brief summary
The main purpose of this study is to measure the effect of tirzepatide on food intake in participants who are overweight or very overweight. The study will also use imaging to learn more about how tirzepatide affects specific parts of the brain. The effect of tirzepatide on appetite will also be studied. The study will last up to about four months and will include up to 14 visits to the study center.
Interventions
DRUGTirzepatide
Administered SC.
DRUGPlacebo
Administered SC.
DRUGLiraglutide
Administered SC.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Tirzepatide and placebo dosing are double-blind. Liraglutide dosing is open label.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have stable body weight for the past 1 month prior to screening * Have a body mass index (BMI) between 27 to 50 kilograms per meter squared (kg/m²), inclusive at screening * Willing and agreeable to commit to the duration of the study and undergo study procedures as instructed by the clinic staff * Women must not be pregnant or breastfeeding
Exclusion criteria
* Have undergone or plan to undergo gastric bypass or bariatric surgery * Have claustrophobia or have ferromagnetic implants that can interfere with completion of fMRI measurements * Have other medical conditions or medical history that make participation in the study unsafe or which may interfere in the interpretation of the results of the study * Unwilling to comply with smoking and alcohol restrictions during the study * Have received prescription drugs or over the counter drugs that promote weight loss in the past 6 months prior to screening * Have a diagnosis of type 2 diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Calorie Intake in Participants Receiving Tirzepatide or Placebo at Week 3 | Baseline, Week 3 | Change from baseline in calorie intake in participants receiving tirzepatide or placebo at week 3 is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Baseline, Week 3 | Change from baseline in BOLD fMRI signals in response to images of highly palatable foods (high fat-high sugar and high fat-high carbohydrate) relative to nonfood items during the fasting state in the brain reward areas (Insula, medial frontal gyrus, superior temporal gyrus, precentral gyrus, and cingulate gyrus) at Week 3 is reported. fMRI is a functional neuroimaging procedure that uses MRI technology to measure brain activity by detecting associated changes in blood flow. When an area of the brain is in use, blood flow to that region increases. The activation in response to the processing of viewing food images in each brain reward areas was measured by the signal change in BOLD response. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) model with covariates Baseline + Treatment + Baseline Body mass index (BMI) Stratum + Scanner Identification + Week + Treatment\*Week + Participant + Random Error. |
| Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score | Baseline, Week 3 | The VAS determines the effects on appetite sensations and desire for specific foods. It consists of 8 individual questions that measure hunger, satiety, fullness, prospective food consumption, desire for sweet food, desire for salty food, desire for savory food, and desire for fatty food. The VAS scales will be analyzed as continuous variables on the 0-100 scale for 8 individual components. Hunger, satiety, fullness, prospective food consumption are rated as 0=Not at all and 100=Extremely. Desire for sweet food, desire for salty food, desire for savory food, and desire for fatty food are rated as 0=Yes, very much and 100=No, not at all. Overall appetite score is calculated as the average of the first 4 individual scores (satiety + fullness + \[100-prospective food consumption\] + \[100-hunger\]/4). The higher overall appetite score indicates less appetite, and the lower score indicates more appetite. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered into the SC tissue of the abdominal wall. | 39 |
| Tirzepatide Participants received tirzepatide 5 mg QW for Weeks 1 through 3 followed by tirzepatide 10 mg QW for Weeks 4 through 6 into the SC tissue of the abdominal wall. | 37 |
| Liraglutide Participants received Liraglutide with step wise dose escalation regimen starting from 0.6 mg QD for week 1 followed by 1.2 mg QD for week 2, 1.8 mg QD for week 3, 2.4 mg QD for Week 4 followed by 3 mg QD starting in Week 5 and maintained for 10 days administered into the SC tissue of the abdominal wall. | 38 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Liraglutide | Tirzepatide |
|---|---|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 9.5 | 44.9 years STANDARD_DEVIATION 10.5 | 43.7 years STANDARD_DEVIATION 11.9 | 44.8 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 108 Participants | 35 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 30 Participants | 10 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 83 Participants | 28 Participants | 27 Participants |
| Region of Enrollment United States | 39 Participants | 114 Participants | 38 Participants | 37 Participants |
| Sex: Female, Male Female | 36 Participants | 97 Participants | 25 Participants | 36 Participants |
| Sex: Female, Male Male | 3 Participants | 17 Participants | 13 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 37 | 0 / 38 |
| other Total, other adverse events | 11 / 39 | 29 / 37 | 20 / 38 |
| serious Total, serious adverse events | 0 / 39 | 0 / 37 | 1 / 38 |
Outcome results
Primary
Change From Baseline in Calorie Intake in Participants Receiving Tirzepatide or Placebo at Week 3
Change from baseline in calorie intake in participants receiving tirzepatide or placebo at week 3 is reported.
Time frame: Baseline, Week 3
Population: All randomized participants who received at least 1 dose of the placebo or tirzepatide and had evaluable data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Calorie Intake in Participants Receiving Tirzepatide or Placebo at Week 3 | 10.95 kilocalories (kcal) | Standard Error 49.06 |
| Tirzepatide | Change From Baseline in Calorie Intake in Participants Receiving Tirzepatide or Placebo at Week 3 | -523.15 kilocalories (kcal) | Standard Error 52.78 |
p-value: <0.000195% CI: [-668.2, -400.02]ANCOVA
Secondary
Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas
Change from baseline in BOLD fMRI signals in response to images of highly palatable foods (high fat-high sugar and high fat-high carbohydrate) relative to nonfood items during the fasting state in the brain reward areas (Insula, medial frontal gyrus, superior temporal gyrus, precentral gyrus, and cingulate gyrus) at Week 3 is reported. fMRI is a functional neuroimaging procedure that uses MRI technology to measure brain activity by detecting associated changes in blood flow. When an area of the brain is in use, blood flow to that region increases. The activation in response to the processing of viewing food images in each brain reward areas was measured by the signal change in BOLD response. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) model with covariates Baseline + Treatment + Baseline Body mass index (BMI) Stratum + Scanner Identification + Week + Treatment\*Week + Participant + Random Error.
Time frame: Baseline, Week 3
Population: All randomized participants who received at least 1 dose of the study drug and had evaluable data. Overall number of participants analyzed are the participants who were evaluable for the outcome measure and number analyzed includes participants who were evaluable for the given categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Precentral gyrus | 0.0441 Arbitrary Units | Standard Error 0.058 |
| Placebo | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Superior temporal gyrus | 0.0132 Arbitrary Units | Standard Error 0.0838 |
| Placebo | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Insula | -0.0739 Arbitrary Units | Standard Error 0.074 |
| Placebo | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Medial frontal gyrus | 0.0504 Arbitrary Units | Standard Error 0.0649 |
| Placebo | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Cingulate gyrus | 0.0283 Arbitrary Units | Standard Error 0.0615 |
| Tirzepatide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Superior temporal gyrus | 0.0174 Arbitrary Units | Standard Error 0.0881 |
| Tirzepatide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Insula | -0.0301 Arbitrary Units | Standard Error 0.0771 |
| Tirzepatide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Medial frontal gyrus | 0.0494 Arbitrary Units | Standard Error 0.068 |
| Tirzepatide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Precentral gyrus | 0.0249 Arbitrary Units | Standard Error 0.0616 |
| Tirzepatide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Cingulate gyrus | 0.0214 Arbitrary Units | Standard Error 0.0643 |
| Liraglutide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Cingulate gyrus | 0.0967 Arbitrary Units | Standard Error 0.0623 |
| Liraglutide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Precentral gyrus | 0.0845 Arbitrary Units | Standard Error 0.0593 |
| Liraglutide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Insula | 0.0190 Arbitrary Units | Standard Error 0.0738 |
| Liraglutide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Superior temporal gyrus | 0.0621 Arbitrary Units | Standard Error 0.0839 |
| Liraglutide | Change From Baseline in Blood Oxygen Level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signals in Response to Images of Highly Palatable Food Relative to Nonfood Item During Fasting State in the 5 Brain Reward Areas | Medial frontal gyrus | 0.0581 Arbitrary Units | Standard Error 0.0658 |
Comparison: Insulap-value: 0.543795% CI: [-0.0994, 0.1871]Mixed Models Analysis
Comparison: Insulap-value: 0.180695% CI: [-0.0441, 0.2301]Mixed Models Analysis
Comparison: Insulap-value: 0.47295% CI: [-0.1846, 0.0863]Mixed Models Analysis
Comparison: Medial frontal gyrusp-value: 0.984295% CI: [-0.1079, 0.1058]Mixed Models Analysis
Comparison: Medial frontal gyrusp-value: 0.882295% CI: [-0.0949, 0.1102]Mixed Models Analysis
Comparison: Medial frontal gyrusp-value: 0.865795% CI: [-0.1111, 0.0937]Mixed Models Analysis
Comparison: Superior temporal gyrusp-value: 0.959995% CI: [-0.165, 0.1736]Mixed Models Analysis
Comparison: Superior temporal gyrusp-value: 0.54995% CI: [-0.1129, 0.2107]Mixed Models Analysis
Comparison: Superior temporal gyrusp-value: 0.585495% CI: [-0.2068, 0.1176]Mixed Models Analysis
Comparison: Precentral gyrusp-value: 0.720395% CI: [-0.1259, 0.0874]Mixed Models Analysis
Comparison: Precentral gyrusp-value: 0.43395% CI: [-0.0617, 0.1425]Mixed Models Analysis
Comparison: Precentral gyrusp-value: 0.248895% CI: [-0.1619, 0.0426]Mixed Models Analysis
Comparison: Cingulate gyrusp-value: 0.888695% CI: [-0.1059, 0.0919]Mixed Models Analysis
Comparison: Cingulate gyrusp-value: 0.156395% CI: [-0.0267, 0.1635]Mixed Models Analysis
Comparison: Cingulate gyrusp-value: 0.118295% CI: [-0.1704, 0.0196]Mixed Models Analysis
Secondary
Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score
The VAS determines the effects on appetite sensations and desire for specific foods. It consists of 8 individual questions that measure hunger, satiety, fullness, prospective food consumption, desire for sweet food, desire for salty food, desire for savory food, and desire for fatty food. The VAS scales will be analyzed as continuous variables on the 0-100 scale for 8 individual components. Hunger, satiety, fullness, prospective food consumption are rated as 0=Not at all and 100=Extremely. Desire for sweet food, desire for salty food, desire for savory food, and desire for fatty food are rated as 0=Yes, very much and 100=No, not at all. Overall appetite score is calculated as the average of the first 4 individual scores (satiety + fullness + \[100-prospective food consumption\] + \[100-hunger\]/4). The higher overall appetite score indicates less appetite, and the lower score indicates more appetite.
Time frame: Baseline, Week 3
Population: All randomized participants who received at least 1 dose of the study drug and had evaluable data. Overall number of participants analyzed are the participants who were evaluable for the outcome measure and number analyzed includes participants who were evaluable for the given categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score | Fasting (Pre-lunch) | 2.15 score on a scale | Standard Error 3.02 |
| Placebo | Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score | Postprandial (Post-lunch) | -0.59 score on a scale | Standard Error 2.08 |
| Tirzepatide | Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score | Fasting (Pre-lunch) | 22.72 score on a scale | Standard Error 3.3 |
| Tirzepatide | Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score | Postprandial (Post-lunch) | 1.66 score on a scale | Standard Error 2.23 |
| Liraglutide | Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score | Fasting (Pre-lunch) | 8.78 score on a scale | Standard Error 3.11 |
| Liraglutide | Change From Baseline in Fasting and Postprandial Overall Appetite Visual Analog Scale (VAS) Score | Postprandial (Post-lunch) | 0.05 score on a scale | Standard Error 2.12 |
Comparison: Fasting (Pre-lunch)p-value: <0.000195% CI: [12.11, 29.02]Mixed Models Analysis
Comparison: Fasting (Pre-lunch)p-value: 0.109795% CI: [-1.53, 14.79]Mixed Models Analysis
Comparison: Fasting (Pre-lunch)p-value: 0.001595% CI: [5.49, 22.38]Mixed Models Analysis
Comparison: Postprandial (Post-lunch)p-value: 0.446995% CI: [-3.6, 8.09]Mixed Models Analysis
Comparison: Postprandial (Post-lunch)p-value: 0.822795% CI: [-5.02, 6.31]Mixed Models Analysis
Comparison: Postprandial (Post-lunch)p-value: 0.586195% CI: [-4.23, 7.45]Mixed Models Analysis