Obesity, Overweight
Conditions
Keywords
Diet, Exercise, Metabolism and Nutrition Disorder, Behavioral Modification
Brief summary
This is a study of tirzepatide in participants with obesity. The purpose of this study is to learn more about how tirzepatide maintains body weight or adds to weight loss after an intensive lifestyle modification program. The study will last about 2 years (29 visits).
Interventions
DRUGTirzepatide
Administered SC
OTHERPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 and previously diagnosed with at least 1 of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease * History of at least one unsuccessful dietary effort to lose body weight
Exclusion criteria
* Diabetes mellitus * Change in body weight greater than 5 kg within 3 months prior to starting study * Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity * History of pancreatitis * Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) * History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years * Any lifetime history of a suicide attempt
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight | Baseline, 72 Weeks | Percent change from baseline in body weight. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction | Week 72 | Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression model using imputed data with baseline body weight, Analysis Country, Sex, Treatment as factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve ≥15% Body Weight Reduction | 72 Weeks | Percentage of participants who achieve ≥15% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors. |
| Percentage of Participants Who Achieve ≥20% Body Weight Reduction | 72 Weeks | Percentage of participants who achieve ≥20% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors. |
| Change From Baseline in Waist Circumference | Baseline, 72 Weeks | Change from baseline in waist circumference. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Body Weight | Baseline, 72 Weeks | Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Body Mass Index (BMI) | Baseline, 72 Weeks | Change from baseline in BMI. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Systolic Blood Pressure (SBP) | Baseline, 72 Weeks | Change from baseline in SBP. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Diastolic Blood Pressure (DBP) | Baseline, 72 Weeks | Change from baseline in DBP. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percent Change From Baseline in Total Cholesterol | Baseline, 72 Weeks | Percent change from baseline in total cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol | Baseline, 72 Weeks | Percent change from baseline in HDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants Who Maintain ≥80% of the Body Weight Lost During Intensive Lifestyle Program | 72 Weeks | Percentage of participants who maintain ≥80% of the body weight lost during intensive lifestyle program was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors. |
| Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol | Baseline, 72 Weeks | Percent change from baseline in VLDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percent Change From Baseline in Triglycerides | Baseline, 72 Weeks | Percent change from baseline in triglycerides. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percent Change From Baseline in Free Fatty Acids | Baseline, 72 Weeks | Percent change from baseline in free fatty acids. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Fasting Glucose | Baseline, 72 Weeks | Change from baseline in fasting glucose. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Hemoglobin A1c (HbA1c) | Baseline, 72 Weeks | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percent Change From Baseline in Fasting Insulin | Baseline, 72 Weeks | Percent change from baseline in fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Short Form 36 Version 2 Health Survey Version 2 (SF 36v2) Acute Form Physical Functioning Domain Score | Baseline, 72 Weeks | The SF-36v2 acute form assesses health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health now and consists of 10-items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores. LS mean was determined using analysis of covariance (ANCOVA) model using Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment (Type III sum of squares) as variables. |
| Change From Baseline in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score | Baseline, 72 Weeks | The IWQOL Lite-CT consists of 20 items, assessing 2 primary domains of obesity related HRQoL: Physical (7 items) and Psychosocial (13 items). A 5-item subset of the Physical domain - the Physical Function composite - is also supported. Items in the Physical Function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency (never to always) scale or a 5-point truth (not at all true to completely true) scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better health-related quality of life. LS mean was determined using ANCOVA model with Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment (Type III sum of squares) as variables. |
| Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol | Baseline, 72 Weeks | Percent change from baseline in LDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants Who Achieve ≥10%Body Weight Reduction | 72 Weeks | Percentage of participants who achieve ≥10% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors. |
Countries
Argentina, Brazil, Puerto Rico, United States
Participant flow
Pre-assignment details
There was a 12-week lead-in period wherein the participants underwent intensive lifestyle modification program to reduce their daily caloric energy intake and increase their physical activity, followed by which they were randomized to receive Tirzepatide or Placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo SC QW. | 292 |
| Tirzepatide Participants received weekly doses of tirzepatide SC for 72 weeks, starting at 2.5 mg for 4 weeks. Subsequently, the dose was increased by 2.5 mg every 4 weeks up to the MTD of either 10 mg or 15 mg. | 287 |
| Total | 579 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 24 | 12 |
| Overall Study | Other - as reported by the investigator | 6 | 0 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Pregnancy | 2 | 2 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 28 | 14 |
Baseline characteristics
| Characteristic | Tirzepatide | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 45.40 years STANDARD_DEVIATION 12.59 | 45.60 years STANDARD_DEVIATION 12.18 | 45.70 years STANDARD_DEVIATION 11.79 |
| Body weight | 102.47 Kilograms (kg) STANDARD_DEVIATION 22.11 | 101.87 Kilograms (kg) STANDARD_DEVIATION 21.39 | 101.29 Kilograms (kg) STANDARD_DEVIATION 20.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 151 Participants | 312 Participants | 161 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 261 Participants | 129 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 63 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 246 Participants | 498 Participants | 252 Participants |
| Region of Enrollment Argentina | 43 Participants | 87 Participants | 44 Participants |
| Region of Enrollment Brazil | 59 Participants | 119 Participants | 60 Participants |
| Region of Enrollment United States | 185 Participants | 373 Participants | 188 Participants |
| Sex: Female, Male Female | 181 Participants | 364 Participants | 183 Participants |
| Sex: Female, Male Male | 106 Participants | 215 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 292 | 1 / 287 |
| other Total, other adverse events | 172 / 292 | 230 / 287 |
| serious Total, serious adverse events | 14 / 292 | 17 / 287 |
Outcome results
Primary
Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction
Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression model using imputed data with baseline body weight, Analysis Country, Sex, Treatment as factors.
Time frame: Week 72
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction | 10.65 percentage of participants |
| Tirzepatide | Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction | 94.37 percentage of participants |
p-value: <0.00195% CI: [69.98, 242.84]Regression, Logistic
Primary
Percent Change From Baseline in Body Weight
Percent change from baseline in body weight. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Weight | 3.3 Percent change | Standard Error 0.6 |
| Tirzepatide | Percent Change From Baseline in Body Weight | -21.1 Percent change | Standard Error 0.59 |
p-value: <0.00195% CI: [-26.1, -22.8]Mixed Models Analysis
Secondary
Change From Baseline in Body Mass Index (BMI)
Change from baseline in BMI. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Mass Index (BMI) | 1.2 kilogram per meter square (kg/m^2) | Standard Error 0.23 |
| Tirzepatide | Change From Baseline in Body Mass Index (BMI) | -7.7 kilogram per meter square (kg/m^2) | Standard Error 0.23 |
p-value: <0.00195% CI: [-9.6, -8.3]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight | 3.5 kg | Standard Error 0.67 |
| Tirzepatide | Change From Baseline in Body Weight | -21.5 kg | Standard Error 0.65 |
p-value: <0.00195% CI: [-26.9, -23.2]Mixed Models Analysis
Secondary
Change From Baseline in Diastolic Blood Pressure (DBP)
Change from baseline in DBP. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Diastolic Blood Pressure (DBP) | 2.3 mmHg | Standard Error 0.53 |
| Tirzepatide | Change From Baseline in Diastolic Blood Pressure (DBP) | -3.4 mmHg | Standard Error 0.51 |
p-value: <0.00195% CI: [-7.2, -4.3]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Glucose
Change from baseline in fasting glucose. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Glucose | 2.4 Milligram per deciliter (mg/dL) | Standard Error 0.86 |
| Tirzepatide | Change From Baseline in Fasting Glucose | -8.8 Milligram per deciliter (mg/dL) | Standard Error 0.82 |
p-value: <0.00195% CI: [-13.5, -8.8]Mixed Models Analysis
Secondary
Change From Baseline in Hemoglobin A1c (HbA1c)
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) | 0.01 Percentage of HbA1c | Standard Deviation 0.022 |
| Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) | -0.46 Percentage of HbA1c | Standard Deviation 0.02 |
p-value: <0.00195% CI: [-0.53, -0.42]Mixed Models Analysis
Secondary
Change From Baseline in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score
The IWQOL Lite-CT consists of 20 items, assessing 2 primary domains of obesity related HRQoL: Physical (7 items) and Psychosocial (13 items). A 5-item subset of the Physical domain - the Physical Function composite - is also supported. Items in the Physical Function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency (never to always) scale or a 5-point truth (not at all true to completely true) scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better health-related quality of life. LS mean was determined using ANCOVA model with Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment (Type III sum of squares) as variables.
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score | 1.1 score on a scale | Standard Error 1.17 |
| Tirzepatide | Change From Baseline in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score | 13.9 score on a scale | Standard Error 1.1 |
p-value: <0.00195% CI: [9.7, 16]ANCOVA
Secondary
Change From Baseline in Short Form 36 Version 2 Health Survey Version 2 (SF 36v2) Acute Form Physical Functioning Domain Score
The SF-36v2 acute form assesses health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health now and consists of 10-items, each rated on a 3-point Likert scale. Scoring of the domain is norm-based and presented in the form of T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function. Range cannot be specified in norm-based scores. LS mean was determined using analysis of covariance (ANCOVA) model using Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment (Type III sum of squares) as variables.
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Short Form 36 Version 2 Health Survey Version 2 (SF 36v2) Acute Form Physical Functioning Domain Score | -0.6 T-score | Standard Error 0.39 |
| Tirzepatide | Change From Baseline in Short Form 36 Version 2 Health Survey Version 2 (SF 36v2) Acute Form Physical Functioning Domain Score | 3.3 T-score | Standard Error 0.37 |
p-value: <0.00195% CI: [2.8, 4.9]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP)
Change from baseline in SBP. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) | 4.4 millimeters of mercury (mmHg) | Standard Error 0.76 |
| Tirzepatide | Change From Baseline in Systolic Blood Pressure (SBP) | -5.8 millimeters of mercury (mmHg) | Standard Error 0.73 |
p-value: <0.00195% CI: [-12.2, -8.1]Mixed Models Analysis
Secondary
Change From Baseline in Waist Circumference
Change from baseline in waist circumference. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Waist Circumference | 1.1 Centimeters (Cms) | Standard Error 0.58 |
| Tirzepatide | Change From Baseline in Waist Circumference | -16.8 Centimeters (Cms) | Standard Error 0.56 |
p-value: <0.00195% CI: [-19.5, -16.3]Mixed Models Analysis
Secondary
Percentage of Participants Who Achieve ≥10%Body Weight Reduction
Percentage of participants who achieve ≥10% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.
Time frame: 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥10%Body Weight Reduction | 4.81 percentage of participants |
| Tirzepatide | Percentage of Participants Who Achieve ≥10%Body Weight Reduction | 88.03 percentage of participants |
p-value: <0.00195% CI: [78.9, 300.37]Regression, Logistic
Secondary
Percentage of Participants Who Achieve ≥15% Body Weight Reduction
Percentage of participants who achieve ≥15% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.
Time frame: 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥15% Body Weight Reduction | 2.06 Percentage of participants |
| Tirzepatide | Percentage of Participants Who Achieve ≥15% Body Weight Reduction | 73.94 Percentage of participants |
p-value: <0.00195% CI: [62.65, 333.21]Regression, Logistic
Secondary
Percentage of Participants Who Achieve ≥20% Body Weight Reduction
Percentage of participants who achieve ≥20% body weight reduction was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.
Time frame: 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥20% Body Weight Reduction | 1.03 Percentage of participants |
| Tirzepatide | Percentage of Participants Who Achieve ≥20% Body Weight Reduction | 54.93 Percentage of participants |
p-value: <0.00195% CI: [40.08, 347.74]Regression, Logistic
Secondary
Percentage of Participants Who Maintain ≥80% of the Body Weight Lost During Intensive Lifestyle Program
Percentage of participants who maintain ≥80% of the body weight lost during intensive lifestyle program was analysed by logistic regression model using imputed data with baseline body weight, analysis country, sex, treatment as factors.
Time frame: 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Maintain ≥80% of the Body Weight Lost During Intensive Lifestyle Program | 37.80 percentage of participants |
| Tirzepatide | Percentage of Participants Who Maintain ≥80% of the Body Weight Lost During Intensive Lifestyle Program | 98.59 percentage of participants |
p-value: <0.00195% CI: [39.17, 263.55]Regression, Logistic
Secondary
Percent Change From Baseline in Fasting Insulin
Percent change from baseline in fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Insulin | 17.3 Percent change | Standard Error 4.95 |
| Tirzepatide | Percent Change From Baseline in Fasting Insulin | -39.1 Percent change | Standard Error 2.46 |
p-value: <0.00195% CI: [-53.7, -41.7]Mixed Models Analysis
Secondary
Percent Change From Baseline in Free Fatty Acids
Percent change from baseline in free fatty acids. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Free Fatty Acids | -15.0 Percent change | Standard Error 2.95 |
| Tirzepatide | Percent Change From Baseline in Free Fatty Acids | -33.1 Percent change | Standard Error 2.2 |
p-value: <0.00195% CI: [-28.4, -13.6]Mixed Models Analysis
Secondary
Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol
Percent change from baseline in HDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol | 3.6 Percent change | Standard Error 1.12 |
| Tirzepatide | Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol | 15.4 Percent change | Standard Error 1.19 |
p-value: <0.00195% CI: [8.2, 14.7]Mixed Models Analysis
Secondary
Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol
Percent change from baseline in LDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol | 6.14 Percent change | Standard Error 1.71 |
| Tirzepatide | Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol | -6.07 Percent change | Standard Error 1.44 |
p-value: <0.00195% CI: [-15.3, -7.53]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total Cholesterol
Percent change from baseline in total cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Cholesterol | 5.19 Percent change | Standard Error 1.11 |
| Tirzepatide | Percent Change From Baseline in Total Cholesterol | -3.00 Percent change | Standard Error 0.97 |
p-value: <0.00195% CI: [-10.4, -5.1]Mixed Models Analysis
Secondary
Percent Change From Baseline in Triglycerides
Percent change from baseline in triglycerides. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Triglycerides | 3.0 Percent change | Standard Error 2.34 |
| Tirzepatide | Percent Change From Baseline in Triglycerides | -25.8 Percent change | Standard Error 1.61 |
p-value: <0.00195% CI: [-32.3, -23.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol
Percent change from baseline in VLDL cholesterol. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Analysis Country + Sex + Lead-In Weight Loss % + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, 72 Weeks
Population: All randomly assigned participants who took at least 1 dose of study drug, had a baseline and at least 1 post- baseline value for this outcome, excluding data after discontinuation of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol | 3.0 Percent change | Standard Error 2.32 |
| Tirzepatide | Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol | -25.6 Percent change | Standard Error 1.6 |
p-value: <0.00195% CI: [-32.1, -23.2]Mixed Models Analysis