Obesity, Overweight
Conditions
Keywords
Metabolism and Nutrition Disorder, Prediabetes
Brief summary
This is a study of tirzepatide in participants with overweight and obesity. The main purpose is to learn more about how tirzepatide affects body weight. The study has two phases: A main phase and an extension phase. The main phase of the study will last 72 weeks. Participants with prediabetes will continue in the extension for another 2 years.
Interventions
DRUGTirzepatide
Administered SC
DRUGPlacebo
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
* Body mass Index (BMI) ≥30 kilograms per square meter (kg/m²), or ≥27 kg/m² and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, 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 (Primary Treatment Period) | Baseline, Week 72 | Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period) | Week 72 | Percentage of participants who achieve greater than or equal to( ≥) 5% body weight reduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period) | Week 72 | Percentage of participants who achieve ≥15% body weight reduction. |
| Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period) | Week 72 | Percentage of participants who achieve ≥20% body weight reduction. |
| Change From Baseline in Waist Circumference (Primary Treatment Period) | Baseline, Week 72 | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 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 while the remaining domains assess functioning in the past week. Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. |
| Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation. |
| Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. |
| Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. |
| Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | Fasting Insulin is a test used to measure the amount of insulin in the body. Results are reported as model-based estimates and SE from MMRM analysis using log transformation. |
| Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | Baseline, Week 176 | LS Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization) | Baseline through Week 176 | The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored. |
| Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 20 | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period | Baseline, Week 72 | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period | Baseline, Week 72 | 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 calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Change From Baseline in Fasting Glucose (Primary Treatment Period) | Baseline, Week 72 | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. |
| Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. |
| Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | Results are reported as model-based estimate and SE from MMRM analysis using log transformation. |
| Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | Baseline, Week 72 | LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model. |
| Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | Week 176 | Percentage of Participants Who Achieve ≥5% Body Weight Reduction. |
| Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period) | Baseline, Week 72 | The IWQOL-Lite-CT is a 20-item, obesity-specific patient-reported outcomes (PRO) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (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 quality of life. |
| Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period) | Week 8, 16, and 36, at 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose | PK: Steady State AUC of Tirzepatide. each participant will be assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose. |
| Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization) | Baseline through Week 193 | The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored. |
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period) | Week 72 | Percentage of Participants who Achieve ≥10% Body Weight Reduction |
Countries
Argentina, Brazil, China, India, Japan, Mexico, Puerto Rico, Russia, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of a matching placebo, administered over a period of 72 weeks. | 643 |
| 5 mg Tirzepatide Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks until reaching a dose of 5 mg, which was then maintained up to week 72. | 630 |
| 10 mg Tirzepatide Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks until reaching a dose of 10 mg, which was then maintained up to week 72. | 636 |
| 15 mg Tirzepatide Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks until reaching a dose of 15 mg, which was then maintained up to week 72. | 630 |
| Total | 2,539 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Additional Treatment Period | Adverse Event | 1 | 2 | 1 | 0 |
| Additional Treatment Period | Death | 0 | 0 | 1 | 1 |
| Additional Treatment Period | Lost to Follow-up | 6 | 4 | 8 | 6 |
| Additional Treatment Period | Other - as reported by the investigator | 2 | 5 | 2 | 0 |
| Additional Treatment Period | Physician Decision | 0 | 0 | 1 | 0 |
| Additional Treatment Period | Pregnancy | 0 | 0 | 0 | 1 |
| Additional Treatment Period | Protocol deviation | 0 | 0 | 1 | 0 |
| Additional Treatment Period | Site closed | 1 | 0 | 1 | 0 |
| Additional Treatment Period | Withdrawal by Subject | 21 | 15 | 3 | 7 |
| Primary Treatment Period | Adverse Event | 6 | 4 | 8 | 6 |
| Primary Treatment Period | Death | 4 | 4 | 2 | 1 |
| Primary Treatment Period | Lost to Follow-up | 41 | 17 | 15 | 13 |
| Primary Treatment Period | Other - as reported by the investigator | 21 | 7 | 6 | 12 |
| Primary Treatment Period | Physician Decision | 0 | 0 | 3 | 1 |
| Primary Treatment Period | Pregnancy | 4 | 3 | 4 | 1 |
| Primary Treatment Period | Withdrawal by Subject | 58 | 26 | 32 | 21 |
| Safety Follow-up Period | Adverse Event | 6 | 8 | 9 | 16 |
| Safety Follow-up Period | Lost to Follow-up | 4 | 4 | 10 | 3 |
| Safety Follow-up Period | Missing Weight at Week 176 | 3 | 2 | 2 | 2 |
| Safety Follow-up Period | Other - as reported by the investigator | 10 | 5 | 6 | 5 |
| Safety Follow-up Period | Physician Decision | 1 | 0 | 0 | 1 |
| Safety Follow-up Period | Pregnancy | 1 | 3 | 0 | 6 |
| Safety Follow-up Period | Protocol deviation | 1 | 0 | 0 | 0 |
| Safety Follow-up Period | Withdrawal by Subject | 31 | 13 | 7 | 9 |
Baseline characteristics
| Characteristic | Placebo | 5 mg Tirzepatide | 10 mg Tirzepatide | 15 mg Tirzepatide | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.4 years STANDARD_DEVIATION 12.5 | 45.6 years STANDARD_DEVIATION 12.7 | 44.7 years STANDARD_DEVIATION 12.4 | 44.9 years STANDARD_DEVIATION 12.3 | 44.9 years STANDARD_DEVIATION 12.5 |
| Baseline Body Weight | 104.9 kilograms (kg) STANDARD_DEVIATION 21.37 | 102.88 kilograms (kg) STANDARD_DEVIATION 20.71 | 105.84 kilograms (kg) STANDARD_DEVIATION 23.32 | 105.59 kilograms (kg) STANDARD_DEVIATION 22.92 | 104.78 kilograms (kg) STANDARD_DEVIATION 22.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 58 Participants | 56 Participants | 58 Participants | 59 Participants | 231 Participants |
| Race (NIH/OMB) Asian | 71 Participants | 68 Participants | 71 Participants | 66 Participants | 276 Participants |
| Race (NIH/OMB) Black or African American | 55 Participants | 48 Participants | 47 Participants | 51 Participants | 201 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 9 Participants | 6 Participants | 8 Participants | 30 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 450 Participants | 447 Participants | 452 Participants | 443 Participants | 1792 Participants |
| Region of Enrollment Argentina | 93 Participants | 90 Participants | 90 Participants | 91 Participants | 364 Participants |
| Region of Enrollment Brazil | 59 Participants | 59 Participants | 61 Participants | 60 Participants | 239 Participants |
| Region of Enrollment China | 7 Participants | 9 Participants | 7 Participants | 7 Participants | 30 Participants |
| Region of Enrollment India | 8 Participants | 9 Participants | 9 Participants | 6 Participants | 32 Participants |
| Region of Enrollment Japan | 33 Participants | 30 Participants | 30 Participants | 31 Participants | 124 Participants |
| Region of Enrollment Mexico | 108 Participants | 110 Participants | 107 Participants | 108 Participants | 433 Participants |
| Region of Enrollment Russia | 32 Participants | 29 Participants | 30 Participants | 27 Participants | 118 Participants |
| Region of Enrollment Taiwan | 15 Participants | 12 Participants | 15 Participants | 16 Participants | 58 Participants |
| Region of Enrollment United States | 288 Participants | 282 Participants | 287 Participants | 284 Participants | 1141 Participants |
| Sex: Female, Male Female | 436 Participants | 426 Participants | 427 Participants | 425 Participants | 1714 Participants |
| Sex: Female, Male Male | 207 Participants | 204 Participants | 209 Participants | 205 Participants | 825 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 643 | 4 / 630 | 3 / 636 | 2 / 630 |
| other Total, other adverse events | 315 / 643 | 443 / 630 | 451 / 636 | 429 / 630 |
| serious Total, serious adverse events | 53 / 643 | 57 / 630 | 60 / 636 | 50 / 630 |
Outcome results
Primary
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period)
Percentage of participants who achieve greater than or equal to( ≥) 5% body weight reduction.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥5% Body Weight Reduction, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period) | 27.87 Percentage of Participants |
| 5 mg Tirzepatide | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period) | 89.41 Percentage of Participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period) | 96.18 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period) | 96.32 Percentage of Participants |
p-value: <0.00195% CI: [17.43, 33.02]Regression, Logistic
p-value: <0.00195% CI: [46.98, 115.39]Regression, Logistic
p-value: <0.00195% CI: [47.86, 119.03]Regression, Logistic
Primary
Percent Change From Baseline in Body Weight (Primary Treatment Period)
Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Weight (Primary Treatment Period) | -2.4 percent change | Standard Error 0.4 |
| 5 mg Tirzepatide | Percent Change From Baseline in Body Weight (Primary Treatment Period) | -16.0 percent change | Standard Error 0.39 |
| 10 mg Tirzepatide | Percent Change From Baseline in Body Weight (Primary Treatment Period) | -21.4 percent change | Standard Error 0.39 |
| 15 mg Tirzepatide | Percent Change From Baseline in Body Weight (Primary Treatment Period) | -22.5 percent change | Standard Error 0.39 |
p-value: <0.00195% CI: [-14.6, -12.5]Mixed Models Analysis
p-value: <0.00195% CI: [-20, -17.8]Mixed Models Analysis
p-value: <0.00195% CI: [-21.2, -19]Mixed Models Analysis
Secondary
Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period
LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline BMI value, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period | -0.9 kilograms per meter squared (kg/m^2) | Standard Error 0.16 |
| 5 mg Tirzepatide | Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period | -5.9 kilograms per meter squared (kg/m^2) | Standard Error 0.16 |
| 10 mg Tirzepatide | Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period | -8.1 kilograms per meter squared (kg/m^2) | Standard Error 0.16 |
| 15 mg Tirzepatide | Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period | -8.6 kilograms per meter squared (kg/m^2) | Standard Error 0.16 |
p-value: <0.00195% CI: [-5.5, -4.6]Mixed Models Analysis
p-value: <0.00195% CI: [-7.7, -6.8]Mixed Models Analysis
p-value: <0.00195% CI: [-8.2, -7.3]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period
LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 20
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period | -2.5 kilograms | Standard Error 0.22 |
| 5 mg Tirzepatide | Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period | -13.2 kilograms | Standard Error 0.16 |
p-value: <0.00195% CI: [-11.2, -10.1]Mixed Models Analysis
Secondary
Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline DBP value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -1.0 mmHg | Standard Error 0.35 |
| 5 mg Tirzepatide | Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -5.3 mmHg | Standard Error 0.19 |
p-value: <0.00195% CI: [-5, -3.5]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Glucose (Primary Treatment Period)
LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline fasting glucose value, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Glucose (Primary Treatment Period) | 0.86 milligram per deciliter (mg/dL) | Standard Error 0.514 |
| 5 mg Tirzepatide | Change From Baseline in Fasting Glucose (Primary Treatment Period) | -7.73 milligram per deciliter (mg/dL) | Standard Error 0.484 |
| 10 mg Tirzepatide | Change From Baseline in Fasting Glucose (Primary Treatment Period) | -9.73 milligram per deciliter (mg/dL) | Standard Error 0.486 |
| 15 mg Tirzepatide | Change From Baseline in Fasting Glucose (Primary Treatment Period) | -10.55 milligram per deciliter (mg/dL) | Standard Error 0.486 |
p-value: <0.00195% CI: [-9.97, -7.2]Mixed Models Analysis
p-value: <0.00195% CI: [-11.98, -9.21]Mixed Models Analysis
p-value: <0.00195% CI: [-12.8, -10.3]Mixed Models Analysis
Secondary
Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period
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 calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline HbA1c value, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period | -0.07 Percentage of HbA1c | Standard Error 0.012 |
| 5 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period | -0.40 Percentage of HbA1c | Standard Error 0.012 |
| 10 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period | -0.49 Percentage of HbA1c | Standard Error 0.012 |
| 15 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period | -0.51 Percentage of HbA1c | Standard Error 0.012 |
p-value: <0.00195% CI: [-0.36, -0.3]Mixed Models Analysis
p-value: <0.00195% CI: [-0.45, -0.38]Mixed Models Analysis
p-value: <0.00195% CI: [-0.48, -0.41]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 at Week 72 (Primary Treatment Period)
The IWQOL-Lite-CT is a 20-item, obesity-specific patient-reported outcomes (PRO) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (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 quality of life.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline IWQOL-Lite CT value, excluding data after prematurely stopping 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 at Week 72 (Primary Treatment Period) | 10.1 score on a scale | Standard Error 0.78 |
| 5 mg Tirzepatide | Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period) | 17.8 score on a scale | Standard Error 0.73 |
| 10 mg Tirzepatide | Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period) | 20.7 score on a scale | Standard Error 0.73 |
| 15 mg Tirzepatide | Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period) | 21.8 score on a scale | Standard Error 0.73 |
p-value: <0.00195% CI: [5.6, 9.8]ANCOVA
p-value: <0.00195% CI: [8.6, 12.8]ANCOVA
p-value: <0.00195% CI: [9.6, 13.8]ANCOVA
Secondary
Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period
The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 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 while the remaining domains assess functioning in the past week. Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline SF-36v2 value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period | 1.7 score on a scale | Standard Error 0.27 |
| 5 mg Tirzepatide | Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period | 4.0 score on a scale | Standard Error 0.18 |
p-value: <0.00195% CI: [1.6, 2.9]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline SBP value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -1.3 millimeter of mercury (mmHg) | Standard Error 0.48 |
| 5 mg Tirzepatide | Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -8.1 millimeter of mercury (mmHg) | Standard Error 0.27 |
p-value: <0.00195% CI: [-7.9, -5.7]Mixed Models Analysis
Secondary
Change From Baseline in Waist Circumference (Primary Treatment Period)
LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline weight circumference value, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Waist Circumference (Primary Treatment Period) | -3.4 centimeters | Standard Error 0.42 |
| 5 mg Tirzepatide | Change From Baseline in Waist Circumference (Primary Treatment Period) | -14.6 centimeters | Standard Error 0.41 |
| 10 mg Tirzepatide | Change From Baseline in Waist Circumference (Primary Treatment Period) | -19.4 centimeters | Standard Error 0.41 |
| 15 mg Tirzepatide | Change From Baseline in Waist Circumference (Primary Treatment Period) | -19.9 centimeters | Standard Error 0.41 |
p-value: <0.00195% CI: [-12.3, -10]Mixed Models Analysis
p-value: <0.00195% CI: [-17.2, -14.9]Mixed Models Analysis
p-value: <0.00195% CI: [-17.7, -15.4]Mixed Models Analysis
Secondary
Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period)
Percentage of Participants who Achieve ≥10% Body Weight Reduction
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥10% Body Weight Reduction, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period) | 13.54 Percentage of Participants |
| 5 mg Tirzepatide | Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period) | 73.35 Percentage of Participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period) | 85.85 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period) | 90.08 Percentage of Participants |
p-value: <0.00195% CI: [14.15, 25.6]Regression, Logistic
p-value: <0.00195% CI: [31.75, 61.45]Regression, Logistic
p-value: <0.00195% CI: [45.94, 93.77]Regression, Logistic
Secondary
Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period)
Percentage of participants who achieve ≥15% body weight reduction.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥15% body weight reduction, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period) | 5.98 Percentage of Participants |
| 5 mg Tirzepatide | Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period) | 50.24 Percentage of Participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period) | 73.61 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period) | 78.24 Percentage of Participants |
p-value: <0.00195% CI: [11.83, 24.66]Regression, Logistic
p-value: <0.00195% CI: [35.42, 75.88]Regression, Logistic
p-value: <0.00195% CI: [45.23, 98.16]Regression, Logistic
Secondary
Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period)
Percentage of participants who achieve ≥20% body weight reduction.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥20% Body Weight Reduction, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period) | 1.26 Percentage of Participants |
| 5 mg Tirzepatide | Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period) | 31.62 Percentage of Participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period) | 55.48 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period) | 62.88 Percentage of Participants |
p-value: <0.00195% CI: [18.37, 74.22]Regression, Logistic
p-value: <0.00195% CI: [54.5, 219.81]Regression, Logistic
p-value: <0.00195% CI: [74.85, 302.97]Regression, Logistic
Secondary
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)
Percentage of Participants Who Achieve ≥5% Body Weight Reduction.
Time frame: Week 176
Population: Participants with prediabetes at randomization who received at least one dose of study drug and had baseline and at least one post-baseline value for body weight, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | 24.62 Percentage of Participants |
| 5 mg Tirzepatide | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | 90.61 Percentage of Participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | 91.92 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | 94.78 Percentage of Participants |
p-value: <0.000195% CI: [17.73, 50.05]Regression, Logistic
p-value: <0.000195% CI: [20.63, 59.53]Regression, Logistic
p-value: <0.000195% CI: [29.61, 102.34]Regression, Logistic
Secondary
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)
The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.
Time frame: Baseline through Week 176
Population: Participants with prediabetes at randomization who received at least one dose of study drug (including the censored participants). Number of participants censored in Placebo = 236, Pooled 5 mg/10 mg/15 mg Tirzepatide = 753.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization) | 12.6 Percentage of Participants |
| 5 mg Tirzepatide | Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization) | 1.2 Percentage of Participants |
p-value: <0.000195% CI: [0.03, 0.13]Regression, Cox
Secondary
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization)
The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.
Time frame: Baseline through Week 193
Population: Participants with prediabetes at randomization who received at least one dose of study drug (including the censored participants). Number of participants censored in Placebo = 233, Pooled 5 mg/10 mg/15 mg Tirzepatide = 744.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization) | 13.7 Percentage of Participants |
| 5 mg Tirzepatide | Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization) | 2.4 Percentage of Participants |
p-value: <0.000195% CI: [0.07, 0.21]Regression, Cox
Secondary
Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)
LS Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, treatment, time, treatment\*time (Type III sum of squares) in the model.
Time frame: Baseline, Week 176
Population: Participants with prediabetes at randomization who received at least one dose of study drug and had baseline and at least one post-baseline body weight value, excluding data after prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | -2.1 percent change | Standard Error 0.78 |
| 5 mg Tirzepatide | Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | -15.4 percent change | Standard Error 0.74 |
| 10 mg Tirzepatide | Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | -19.9 percent change | Standard Error 0.72 |
| 15 mg Tirzepatide | Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization) | -22.9 percent change | Standard Error 0.73 |
p-value: <0.000195% CI: [-15.3, -11.1]Mixed Models Analysis
p-value: <0.000195% CI: [-19.8, -15.7]Mixed Models Analysis
p-value: <0.000195% CI: [-22.8, -18.6]Mixed Models Analysis
Secondary
Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
Fasting Insulin is a test used to measure the amount of insulin in the body. Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had a baseline and at least one post-baseline fasting insulin value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -9.7 percent change | Standard Error 2.6 |
| 5 mg Tirzepatide | Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -46.9 percent change | Standard Error 0.83 |
p-value: <0.00195% CI: [-44.9, -37.3]Mixed Models Analysis
Secondary
Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline free fatty acids value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | 6.1 percent change | Standard Error 2.65 |
| 5 mg Tirzepatide | Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -5.9 percent change | Standard Error 1.28 |
p-value: <0.00195% CI: [-16.1, -6.2]Mixed Models Analysis
Secondary
Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline total cholesterol HDL value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | 0.25 percent change | Standard Error 0.757 |
| 5 mg Tirzepatide | Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | 7.92 percent change | Standard Error 0.447 |
p-value: <0.00195% CI: [5.85, 9.49]Mixed Models Analysis
Secondary
Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had a baseline and at least one post-baseline LDL value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -0.85 percent change | Standard Error 1.076 |
| 5 mg Tirzepatide | Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -6.86 percent change | Standard Error 0.555 |
p-value: <0.00195% CI: [-8.32, -3.75]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline total cholesterol value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -1.11 percent change | Standard Error 0.695 |
| 5 mg Tirzepatide | Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -5.97 percent change | Standard Error 0.364 |
p-value: <0.00195% CI: [-6.4, -3.41]Mixed Models Analysis
Secondary
Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had a baseline and at least one post-baseline triglyceride value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -6.3 percent change | Standard Error 1.55 |
| 5 mg Tirzepatide | Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -27.6 percent change | Standard Error 0.66 |
p-value: <0.00195% CI: [-25.6, -19.8]Mixed Models Analysis
Secondary
Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period
Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had baseline and at least one post-baseline VLDL value, excluding data after prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -5.6 percent change | Standard Error 1.55 |
| 5 mg Tirzepatide | Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period | -27.6 percent change | Standard Error 0.65 |
p-value: <0.00195% CI: [-26.1, -20.4]Mixed Models Analysis
Secondary
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period)
PK: Steady State AUC of Tirzepatide. each participant will be assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose.
Time frame: Week 8, 16, and 36, at 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose
Population: All randomly assigned participants who are exposed to at least one dose of study drug who had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period) | 88900 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 20.2 |
| 5 mg Tirzepatide | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period) | 177000 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 22 |
| 10 mg Tirzepatide | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period) | 266000 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 20.4 |