Obesity, Overweight
Conditions
Keywords
Metabolism and Nutrition Disorder, Prediabetes
Brief summary
This was a study of tirzepatide in participants with obesity or overweight. The main purpose was to learn more about how tirzepatide maintained body weight loss. The study had two phases: a lead-in phase in which all participants took tirzepatide and a treatment phase in which participants either continued tirzepatide or switched to placebo. The study lasted about 2 years (25 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
* 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 Randomization in Body Weight at Week 88 | Randomization (Week 36), Week 88 | Least square (LS) mean was analysed by mixed model repeated measures (MMRM) model with randomization + analysis country + sex + interactive web response system (IWRS) MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Randomization in Body Weight at Week 64 | Randomization (Week 36), Week 64 | LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Randomization in Body Weight | Randomization (Week 36), Week 88 | LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Randomization in Waist Circumference | Randomization (Week 36), Week 88 | LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Randomization in Body Mass Index (BMI) | Randomization (Week 36), Week 88 | LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Randomization in Fasting Glucose | Randomization (Week 36), Week 88 | LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Randomization in Hemoglobin A1c (HbA1c) | Randomization (Week 36), Week 88 | LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Percent Change From Randomization in Fasting Insulin | Randomization (Week 36), Week 88 | LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | Randomization (Week 36), Week 88 | LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) | Randomization (Week 36), Week 88 | LS mean change was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Baseline in BMI | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + BMI at randomization (kg/m\^2) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Randomization in Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain Score | Randomization (Week 36), Week 88 | 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 analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables. |
| Change From Randomization in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Function Composite Score | Randomization (Week 36), Week 88 | 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 analysed by ANCOVA model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables. |
| Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% During the Open-Label Lead-In Period | Randomization (Week 36) to Week 88 | Time to first occurrence of participants returning to \>95% baseline weight for those who lost ≥5% during the open-label lead-in period. |
| Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | Baseline (Week 0) to Week 88 | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction from baseline was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment\*Time as variables. |
| Change From Baseline in Body Weight | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Percent Change From Baseline in Body Weight | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Baseline in Waist Circumference | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Baseline in Fasting Glucose | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Baseline in HbA1c | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Percent Change From Baseline in Fasting Insulin | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Baseline in SBP, DBP | Baseline (Week 0), Week 88 | LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables. |
| Change From Baseline in SF 36v2 Acute Form - Physical Functioning Domain Score | Baseline (Week 0), Week 88 | 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 analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables. |
| Change From Baseline in IWQOL-Lite-CT - Physical Function Composite Score | Baseline (Week 0), Week 88 | 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 analysed by ANCOVA model with baseline + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables. |
| Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period | Week 88 | Percentage of Participants Who Maintain at least 80% of the Body Weight Lost During the Open-Label Lead-In Period was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment\*Time as variables. |
Countries
Argentina, Brazil, Puerto Rico, Taiwan, United States
Participant flow
Pre-assignment details
* Open-label lead-in period: Baseline (week 0) to week 36: Participants received weekly doses of tirzepatide SC escalated every 4 weeks until they attained a maximum tolerated dose (MTD). * Double-blind study period (randomized period including the safety follow-up): Randomization (week 36) to week 92: At week 36, those who completed the lead-in treatment were randomized 1:1 to tirzepatide MTD and placebo, treated up to week 88, and followed up for safety after 4 weeks off treatment, at week 92.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received weekly doses of placebo SC for 52 weeks. | 335 |
| Tirzepatide MTD Participants continued tirzepatide MTD (either 10 mg or 15 mg) for an additional 52 weeks. | 335 |
| Total | 670 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Study Period (Week 36 - 92) | Death | 0 | 1 | 1 |
| Double-blind Study Period (Week 36 - 92) | Lost to Follow-up | 0 | 10 | 8 |
| Double-blind Study Period (Week 36 - 92) | Other - as reported by the investigator | 0 | 8 | 0 |
| Double-blind Study Period (Week 36 - 92) | Perceived excessive weight loss | 0 | 1 | 0 |
| Double-blind Study Period (Week 36 - 92) | Pregnancy | 0 | 2 | 1 |
| Double-blind Study Period (Week 36 - 92) | Protocol deviation | 0 | 1 | 2 |
| Double-blind Study Period (Week 36 - 92) | Withdrawal by Subject | 0 | 22 | 13 |
| Open-label Lead-in Period (Week 0 - 36) | Adverse Event | 50 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Covid-19 | 1 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Death | 1 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Lost to Follow-up | 14 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Other - as reported by the investigator | 2 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Physician Decision | 1 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Pregnancy | 1 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Protocol deviation | 10 | 0 | 0 |
| Open-label Lead-in Period (Week 0 - 36) | Withdrawal by Subject | 32 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Tirzepatide MTD |
|---|---|---|---|
| Age, Continuous | 47.15 years STANDARD_DEVIATION 12.38 | 47.71 years STANDARD_DEVIATION 12.59 | 48.27 years STANDARD_DEVIATION 12.79 |
| Body weight | 107.79 kilogram (kg) STANDARD_DEVIATION 23.66 | 107.3 kilogram (kg) STANDARD_DEVIATION 22.33 | 106.82 kilogram (kg) STANDARD_DEVIATION 20.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 155 Participants | 296 Participants | 141 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 180 Participants | 373 Participants | 193 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 48 Participants | 26 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 75 Participants | 39 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 273 Participants | 537 Participants | 264 Participants |
| Region of Enrollment Argentina | 56 Participants | 111 Participants | 55 Participants |
| Region of Enrollment Brazil | 46 Participants | 89 Participants | 43 Participants |
| Region of Enrollment Taiwan | 17 Participants | 38 Participants | 21 Participants |
| Region of Enrollment United States | 216 Participants | 432 Participants | 216 Participants |
| Sex: Female, Male Female | 237 Participants | 473 Participants | 236 Participants |
| Sex: Female, Male Male | 98 Participants | 197 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 782 | 1 / 335 | 1 / 335 |
| other Total, other adverse events | 559 / 782 | 100 / 335 | 124 / 335 |
| serious Total, serious adverse events | 16 / 782 | 10 / 335 | 10 / 335 |
Outcome results
Primary
Percent Change From Randomization in Body Weight at Week 88
Least square (LS) mean was analysed by mixed model repeated measures (MMRM) model with randomization + analysis country + sex + interactive web response system (IWRS) MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Randomization in Body Weight at Week 88 | 14.8 percent change | Standard Error 0.53 |
| Tirzepatide MTD | Percent Change From Randomization in Body Weight at Week 88 | -6.7 percent change | Standard Error 0.52 |
p-value: <0.00195% CI: [-22.9, -20]Mixed Models Analysis
Secondary
Change From Baseline in BMI
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + BMI at randomization (kg/m\^2) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in BMI | -3.6 kg/m^2 | Standard Error 0.16 |
| Tirzepatide MTD | Change From Baseline in BMI | -10.0 kg/m^2 | Standard Error 0.15 |
p-value: <0.00195% CI: [-6.8, -6]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight | -10.0 kg | Standard Error 0.43 |
| Tirzepatide MTD | Change From Baseline in Body Weight | -27.6 kg | Standard Error 0.42 |
p-value: <0.00195% CI: [-18.8, -16.4]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Glucose
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Glucose | -1.72 mg/dL | Standard Error 0.543 |
| Tirzepatide MTD | Change From Baseline in Fasting Glucose | -10.63 mg/dL | Standard Error 0.522 |
p-value: <0.00195% CI: [-10.4, -7.43]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c | -0.22 percentage of HbA1c | Standard Error 0.018 |
| Tirzepatide MTD | Change From Baseline in HbA1c | -0.57 percentage of HbA1c | Standard Error 0.017 |
p-value: <0.00195% CI: [-0.39, -0.29]Mixed Models Analysis
Secondary
Change From Baseline in 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 analysed by ANCOVA model with baseline + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in IWQOL-Lite-CT - Physical Function Composite Score | 16.7 score on a scale | Standard Error 1.01 |
| Tirzepatide MTD | Change From Baseline in IWQOL-Lite-CT - Physical Function Composite Score | 26.0 score on a scale | Standard Error 0.97 |
p-value: <0.00195% CI: [6.5, 12]ANCOVA
Secondary
Change From Baseline in SBP, DBP
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in SBP, DBP | SBP | -2.4 mmHg | Standard Error 0.66 |
| Placebo | Change From Baseline in SBP, DBP | DBP | -1.7 mmHg | Standard Error 0.46 |
| Tirzepatide MTD | Change From Baseline in SBP, DBP | SBP | -9.3 mmHg | Standard Error 0.63 |
| Tirzepatide MTD | Change From Baseline in SBP, DBP | DBP | -5.5 mmHg | Standard Error 0.44 |
Comparison: SBPp-value: <0.00195% CI: [-8.7, -5.1]Mixed Models Analysis
Comparison: DBPp-value: <0.00195% CI: [-5.1, -2.6]Mixed Models Analysis
Secondary
Change From Baseline in 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 analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SF 36v2 Acute Form - Physical Functioning Domain Score | 3.7 T-score | Standard Error 0.36 |
| Tirzepatide MTD | Change From Baseline in SF 36v2 Acute Form - Physical Functioning Domain Score | 6.3 T-score | Standard Error 0.34 |
p-value: <0.00195% CI: [1.7, 3.7]ANCOVA
Secondary
Change From Baseline in Waist Circumference
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Waist Circumference | -9.1 cm | Standard Error 0.53 |
| Tirzepatide MTD | Change From Baseline in Waist Circumference | -22.8 cm | Standard Error 0.52 |
p-value: <0.00195% CI: [-15.1, -12.2]Mixed Models Analysis
Secondary
Change From Randomization in Body Mass Index (BMI)
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Randomization in Body Mass Index (BMI) | 4.3 kilogram per square metre (kg/m^2) | Standard Error 0.16 |
| Tirzepatide MTD | Change From Randomization in Body Mass Index (BMI) | -2.1 kilogram per square metre (kg/m^2) | Standard Error 0.15 |
p-value: <0.00195% CI: [-6.8, -6]Mixed Models Analysis
Secondary
Change From Randomization in Body Weight
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Randomization in Body Weight | 11.9 kilogram (kg) | Standard Error 0.43 |
| Tirzepatide MTD | Change From Randomization in Body Weight | -5.7 kilogram (kg) | Standard Error 0.42 |
p-value: <0.00195% CI: [-18.8, -16.4]Mixed Models Analysis
Secondary
Change From Randomization in Fasting Glucose
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Randomization in Fasting Glucose | 7.74 milligrams per deciliter (mg/dL) | Standard Error 0.548 |
| Tirzepatide MTD | Change From Randomization in Fasting Glucose | -0.90 milligrams per deciliter (mg/dL) | Standard Error 0.528 |
p-value: <0.00195% CI: [-10.14, -7.15]Mixed Models Analysis
Secondary
Change From Randomization in Hemoglobin A1c (HbA1c)
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Randomization in Hemoglobin A1c (HbA1c) | 0.25 percentage of HbA1c | Standard Error 0.017 |
| Tirzepatide MTD | Change From Randomization in Hemoglobin A1c (HbA1c) | -0.08 percentage of HbA1c | Standard Error 0.017 |
p-value: <0.00195% CI: [-0.38, -0.28]Mixed Models Analysis
Secondary
Change From Randomization 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 analysed by ANCOVA model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Randomization in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Function Composite Score | -5.0 score on a scale | Standard Error 0.95 |
| Tirzepatide MTD | Change From Randomization in Impact of Weight on Quality of Life Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Function Composite Score | 4.4 score on a scale | Standard Error 0.91 |
p-value: <0.00195% CI: [6.8, 12]ANCOVA
Secondary
Change From Randomization in Short Form 36 Version 2 Health Survey (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 analysed by analysis of covariance (ANCOVA) model with randomization + analysis Country + sex + weight loss at Week 36 (\< 10%, \>= 10%) + IWRS MTD at Week 36 + treatment (type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Randomization in Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain Score | -1.8 T-score | Standard Error 0.32 |
| Tirzepatide MTD | Change From Randomization in Short Form 36 Version 2 Health Survey (SF 36v2) Acute Form - Physical Functioning Domain Score | 0.8 T-score | Standard Error 0.31 |
p-value: <0.00195% CI: [1.7, 3.5]ANCOVA
Secondary
Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
LS mean change was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + Weight Loss at Week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) | SBP | 8.4 millimetre of mercury (mmHg) | Standard Error 0.64 |
| Placebo | Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) | DBP | 3.2 millimetre of mercury (mmHg) | Standard Error 0.44 |
| Tirzepatide MTD | Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) | SBP | 2.1 millimetre of mercury (mmHg) | Standard Error 0.61 |
| Tirzepatide MTD | Change From Randomization in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) | DBP | -0.4 millimetre of mercury (mmHg) | Standard Error 0.42 |
Comparison: SBPp-value: <0.00195% CI: [-8.1, -4.6]Mixed Models Analysis
Comparison: DBPp-value: <0.00195% CI: [-4.8, -2.4]Mixed Models Analysis
Secondary
Change From Randomization in Waist Circumference
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Randomization in Waist Circumference | 8.3 centimetre (cm) | Standard Error 0.44 |
| Tirzepatide MTD | Change From Randomization in Waist Circumference | -4.6 centimetre (cm) | Standard Error 0.43 |
p-value: <0.00195% CI: [-14.1, -11.7]Mixed Models Analysis
Secondary
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline
Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction from baseline was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment\*Time as variables.
Time frame: Baseline (Week 0) to Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥5% body weight reduction from baseline | 69.00 percentage of participants |
| Placebo | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥10% body weight reduction from baseline | 44.38 percentage of participants |
| Placebo | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥15% body weight reduction from baseline | 24.01 percentage of participants |
| Placebo | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥20% body weight reduction from baseline | 11.55 percentage of participants |
| Tirzepatide MTD | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥20% body weight reduction from baseline | 72.59 percentage of participants |
| Tirzepatide MTD | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥5% body weight reduction from baseline | 98.49 percentage of participants |
| Tirzepatide MTD | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥15% body weight reduction from baseline | 87.05 percentage of participants |
| Tirzepatide MTD | Percentage of Participants Who Achieve ≥5%, ≥10%, ≥15%, ≥20% Body Weight Reduction From Baseline | ≥10% body weight reduction from baseline | 93.98 percentage of participants |
Comparison: ≥5% body weight reduction from baselinep-value: <0.00195% CI: [18.32, 121.99]Regression, Logistic
Comparison: ≥10% body weight reduction from baselinep-value: <0.00195% CI: [34.46, 148.39]Regression, Logistic
Comparison: ≥15% body weight reduction from baselinep-value: <0.00195% CI: [42.06, 152.14]Regression, Logistic
Comparison: ≥20% body weight reduction from baselinep-value: <0.00195% CI: [66.06, 300.29]Regression, Logistic
Secondary
Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period
Percentage of Participants Who Maintain at least 80% of the Body Weight Lost During the Open-Label Lead-In Period was analysed by Logistic regression model with missing value imputed by MMRM at week 88. Missing values were imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures with Baseline + Analysis Country + Sex + IWRS MTD at Week 36 + randomization + Treatment + Time + Treatment\*Time as variables.
Time frame: Week 88
Population: All randomized participants who received at least one dose of the study drug, had weight loss in the open label lead-in period and at least one post-randomization value for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period | 13.50 percentage of participants |
| Tirzepatide MTD | Percentage of Participants Who Maintain at Least 80% of the Body Weight Lost During the Open-Label Lead-In Period | 93.37 percentage of participants |
p-value: <0.00195% CI: [54.72, 168.09]Regression, Logistic
Secondary
Percent Change From Baseline in Body Weight
LS mean was analysed by MMRM model with baseline + analysis country + sex + IWRS MTD at Week 36 + body weight at randomization (kg) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Weight | -9.5 percent change | Standard Error 0.4 |
| Tirzepatide MTD | Percent Change From Baseline in Body Weight | -26.0 percent change | Standard Error 0.39 |
p-value: <0.00195% CI: [-17.5, -15.4]Mixed Models Analysis
Secondary
Percent Change From Baseline in Fasting Insulin
LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Insulin | -29.8 percent change | Standard Error 2.52 |
| Tirzepatide MTD | Percent Change From Baseline in Fasting Insulin | -54.1 percent change | Standard Error 1.57 |
p-value: <0.00195% CI: [-40.6, -27.9]Mixed Models Analysis
Secondary
Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs)
LS mean was analysed by MMRM model with log(actual measurement/baseline) = log (baseline) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Baseline (Week 0), Week 88
Population: All randomized participants who received at least one dose of the study drug, had baseline and at least one post-baseline values for the respective lipid parameters, excluding data after discontinuation of the study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | Total Cholesterol | 2.16 percent change | Standard Error 0.919 |
| Placebo | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | LDL Cholesterol | 2.62 percent change | Standard Error 1.371 |
| Placebo | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | HDL Cholesterol | 9.44 percent change | Standard Error 1.093 |
| Placebo | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | VLDL Cholesterol | -15.6 percent change | Standard Error 1.82 |
| Placebo | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | Triglycerides | -15.3 percent change | Standard Error 1.84 |
| Placebo | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | FFA | -9.69 percent change | Standard Error 2.811 |
| Tirzepatide MTD | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | Triglycerides | -33.3 percent change | Standard Error 1.38 |
| Tirzepatide MTD | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | Total Cholesterol | -5.01 percent change | Standard Error 0.817 |
| Tirzepatide MTD | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | VLDL Cholesterol | -32.6 percent change | Standard Error 1.37 |
| Tirzepatide MTD | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | LDL Cholesterol | -5.21 percent change | Standard Error 1.207 |
| Tirzepatide MTD | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | FFA | -20.38 percent change | Standard Error 2.36 |
| Tirzepatide MTD | Percent Change From Baseline in Lipid Parameters (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides, FFAs) | HDL Cholesterol | 12.29 percent change | Standard Error 1.071 |
Comparison: Total Cholesterolp-value: <0.00195% CI: [-9.27, -4.72]Mixed Models Analysis
Comparison: LDL Cholesterolp-value: <0.00195% CI: [-10.91, -4.21]Mixed Models Analysis
Comparison: HDL Cholesterolp-value: 0.06495% CI: [-0.14, 5.43]Mixed Models Analysis
Comparison: VLDL Cholesterolp-value: <0.00195% CI: [-24.7, -15.3]Mixed Models Analysis
Comparison: Triglyceridesp-value: <0.00195% CI: [-25.8, -16.4]Mixed Models Analysis
Comparison: FFAp-value: 0.00495% CI: [-18.98, -4.06]Mixed Models Analysis
Secondary
Percent Change From Randomization in Body Weight at Week 64
LS mean was analysed by MMRM model with randomization + analysis country + sex + IWRS MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 64
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Randomization in Body Weight at Week 64 | 9.9 percent change | Standard Error 0.38 |
| Tirzepatide MTD | Percent Change From Randomization in Body Weight at Week 64 | -6.0 percent change | Standard Error 0.37 |
p-value: <0.00195% CI: [-17, -14.9]Mixed Models Analysis
Secondary
Percent Change From Randomization in Fasting Insulin
LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for this outcome, excluding data after discontinuation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Randomization in Fasting Insulin | 23.3 percent change | Standard Error 4.37 |
| Tirzepatide MTD | Percent Change From Randomization in Fasting Insulin | -15.4 percent change | Standard Error 2.88 |
p-value: <0.00195% CI: [-37.7, -24.4]Mixed Models Analysis
Secondary
Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA))
LS mean was analysed by MMRM model with log(actual measurement/randomization) = log (randomization) + analysis country + sex + IWRS MTD at Week 36 + weight loss at week 36 (\< 10%, \>= 10%) + treatment + time + treatment\*time (Type III sum of squares) as variables.
Time frame: Randomization (Week 36), Week 88
Population: All randomized participants who received at least one dose of the study drug, had randomization and at least one post-randomization values for the respective lipid parameters, excluding data after discontinuation of the study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | Total Cholesterol | 8.30 percent change | Standard Error 0.943 |
| Placebo | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | LDL Cholesterol | 3.43 percent change | Standard Error 1.368 |
| Placebo | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | HDL Cholesterol | 14.6 percent change | Standard Error 1.06 |
| Placebo | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | VLDL Cholesterol | 14.7 percent change | Standard Error 2.32 |
| Placebo | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | Triglycerides | 15.6 percent change | Standard Error 2.39 |
| Placebo | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | FFA | -2.9 percent change | Standard Error 2.98 |
| Tirzepatide MTD | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | Triglycerides | -8.2 percent change | Standard Error 1.81 |
| Tirzepatide MTD | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | Total Cholesterol | 2.29 percent change | Standard Error 0.852 |
| Tirzepatide MTD | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | VLDL Cholesterol | -7.8 percent change | Standard Error 1.77 |
| Tirzepatide MTD | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | LDL Cholesterol | -3.36 percent change | Standard Error 1.218 |
| Tirzepatide MTD | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | FFA | -13.4 percent change | Standard Error 2.54 |
| Tirzepatide MTD | Percent Change From Randomization in Lipid Parameters (Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Very Low Density Lipoprotein (VLDL) Cholesterol, Triglycerides, Free Fatty Acids (FFA)) | HDL Cholesterol | 18.3 percent change | Standard Error 1.05 |
Comparison: Total Cholesterolp-value: <0.00195% CI: [-7.76, -3.28]Mixed Models Analysis
Comparison: LDL Cholesterolp-value: <0.00195% CI: [-9.87, -3.15]Mixed Models Analysis
Comparison: HDL Cholesterolp-value: 0.01495% CI: [0.6, 5.8]Mixed Models Analysis
Comparison: VLDL Cholesterolp-value: <0.00195% CI: [-24, -15.1]Mixed Models Analysis
Comparison: Triglyceridesp-value: <0.00195% CI: [-24.9, -16]Mixed Models Analysis
Comparison: FFAp-value: 0.00895% CI: [-17.9, -3]Mixed Models Analysis
Secondary
Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% During the Open-Label Lead-In Period
Time to first occurrence of participants returning to \>95% baseline weight for those who lost ≥5% during the open-label lead-in period.
Time frame: Randomization (Week 36) to Week 88
Population: All randomized participants who received at least one dose of the study drug, lost \>=5% of their weight in the open label period, excluding data after discontinuation of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% During the Open-Label Lead-In Period | NA weeks |
| Tirzepatide MTD | Time to First Occurrence of Participants Returning to >95% Baseline Weight for Those Who Lost ≥5% During the Open-Label Lead-In Period | NA weeks |
p-value: <0.00195% CI: [0.004, 0.046]Log Rank