Obesity
Conditions
Brief summary
This is a study of tirzepatide in participants with obesity. The main purpose is to learn more about how tirzepatide affects the number of calories participants burn and the amount of food they eat. The study lasted for 28 weeks and will include about 21 visits to the study center.
Interventions
DRUGTirzepatide
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Have body mass index of 30 to 45 kilograms per square meter (kg/m²), inclusive * Have a stable body weight in the past 1 month prior to screening * Willing and agreeable to commit to the duration of the study and undergo study procedures as instructed by the clinic staff
Exclusion criteria
* Have undergone gastric bypass or bariatric surgery * Have a diagnosis of type 2 diabetes * Have a history or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs; of constituting a risk when taking the study drug; or of interfering with the interpretation of data * Have received prescription drugs or over the counter drugs that promote weight loss in the past 6 months prior to screening * Have any lifetime history of a suicide attempt * Patient Health Questionnaire-9 (PHQ-9) score of 15 or more at screening * Positive responses to selected items on the Columbia Suicide Severity Rating Scale (C-SSRS)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 18 in Sleep Metabolic Rate (SMR) | Baseline, Week 18 | SMR was measured using whole-room indirect calorimetry (respiratory chamber). Change from Baseline to Week 18 in SMR was evaluated. Least square (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline, Treatment, Change from Baseline to Week 18 in Fat-Free Mass, Change from baseline to Week 18 in Fat Mass and Random Error as variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 18 in 24-hour Energy Expenditure (EE) | Baseline, Week 18 | 24 hour energy expenditure was measured in a respiratory chamber. LS mean was determined by ANCOVA model with Baseline, Treatment, Change from Baseline to Week 18 in Fat-Free Mass, Change from baseline to Week 18 in Fat Mass and Random Error as variables. |
| Change From Baseline to Week 18 in 24 Hour Respiratory Quotient (RQ) | Baseline, Week 18 | Respiratory quotient was calculated as the ratio of carbon dioxide production to oxygen consumption as measured in a metabolic chamber for 24 continuous hours. Ratio of total carbon dioxide production (VCO2)/total oxygen consumption (VO2), from baseline to Week 18 was evaluated. 24-hour RQ = total VCO2 \[Liter/24hour\] / total VO2 \[Liter/24hour\]. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Sleep RQ | Baseline, Week 18 | Sleep RQ is defined as the ratio of VCO2 to VO2 during sleep time points. Change from baseline to Week 18 in sleep RQ is presented. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Duration of Periods With RQ<0.80 | Baseline, Week 18 | RQ\<0.80 is defined as the cut point for high lipid oxidation of RQ; lipid oxidation will be calculated and corrected for protein oxidation; the total number of minutes with RQ \<0.80, termed lipid oxidation duration, during each 23-hour measurement period will be recorded; protein oxidation will be determined from urine nitrogen that will be collected during 2 periods for each calorimeter day. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation | Baseline, Week 18 | Change from Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation is presented. * Protein Oxidation = 6.25\*\[urinary nitrogen\] * Fat Oxidation = 1.689\*\[total oxygen consumption (VO2)\] - 1.689\*\[total carbon dioxide production (VCO2)\] - 0.324\*\[protein oxidation\] * Carbohydrate Oxidation = 4.113\*\[VCO2\] - 2.907\*\[VO2\] - 0.375\*\[protein oxidation\]. Adjusted oxidation is calculated using the formula, Adjusted oxidation rate (g/day) = oxidation rate (g/day) / 24-hour Energy Expenditure) x 1000 (kcal/day). LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Body Weight (BW) | Baseline, Week 18 | Change from baseline in BW through Week 18 in participants were presented. LS mean was determined by mixed measures repeated model (MMRM) model with Baseline, Treatment, Time, Treatment\*Time, Participant and Random Error as variables. |
| Change From Baseline to Week 18 in Body Fat-Free Mass | Baseline, Week 18 | Change from baseline to Week 18 in body fat free mass is presented. Body fat free mass was measured using dual energy X-ray absorptiometry (DXA) measurements. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Food Intake During Ad Libitum Meal | Baseline, Week 18 | Ad libitum lunch and dinner were provided. The sum of the caloric breakdown (carbohydrates, protein, and fats) was calculated from the respective nutritional information of the food items. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Percentage of Body Fat Mass | Baseline, Week 18 | The total body fat mass was measured in kilograms (kg) using DXA scanning. Change from baseline to week 18 in percentage of body fat mass is reported. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Lipid Metabolism Parameters | Baseline, Week 18 | Change in Lipid Metabolism Parameters from baseline (week 0) to week 18 is evaluated. Triglyceride, Very low density lipoprotein (VLDL), High density lipoprotein (HDL) cholesterol and free fatty acids values were reported. Results below presents Area under the Curve (AUC) during standardized mixed-meal tolerance test (sMMTT). LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Fasting Insulin Resistance | Baseline, Week 18 during standardized mixed meal tolerance test | Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is a test that uses a simultaneous fasting blood glucose test and fasting insulin test to accurately estimate the degree of insulin resistance (IR) and β-cell function (the cells of the pancreas that produce insulin). HOMA-IR= \[Fasting glucose (mmol/L) x (fasting insulin (picomoles per liter {pmol/L})/6)\] / 22.5. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Postprandial Insulin Sensitivity | Baseline, Week 18 | Insulin sensitivity was measured from insulin and glucose levels obtained following standard meal challenge using a modification of the Matsuda index. This was calculated based on data obtained from a 75 g oral glucose tolerance test, as follows: 10,000 divided by the square root of {(fasting glucose X fasting insulin) (total area under the glucose response curve (AUC) 0-4hr)) X total insulin AUC(0-4hr )}. A Matsuda index of \<2.5 indicates whole body insulin resistance. A lower Matsuda Index indicates the worst disease state. An increase in the Matsuda Index indicates an improvement in insulin sensitivity (best). A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening. Stumvoll and oral glucose insulin sensitivity indexes were also used for measuring the insulin Sensitivity. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Postmeal Total Glucose AUC During sMMTT | Baseline, Week 18 | Total AUC from time zero to 4 hours after start of the meal \[AUC0-4 hours\]) during sMMTT was evaluated. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
| Change From Baseline to Week 18 in Hemoglobin A1c (HbA1c) | Baseline, Week 18 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was determined by ANCOVA model with Baseline, Treatment, Time, Treatment\*Time, Participant and Random Error as variables. |
| Change From Baseline to Week 18 in Body Fat Mass | Baseline, Week 18 | Change from baseline to Week 18 in body fat mass is presented. Body fat mass was measured using DXA measurements. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo QW by SC injection. | 28 |
| 15 mg Tirzepatide Participants received 15 mg of tirzepatide QW by SC injection. | 27 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | 15 mg Tirzepatide |
|---|---|---|---|
| Age, Continuous | 48.1 years STANDARD_DEVIATION 10.7 | 46.8 years STANDARD_DEVIATION 10.3 | 45.5 years STANDARD_DEVIATION 9.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 23 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 29 Participants | 14 Participants |
| Region of Enrollment United States | 28 Participants | 55 Participants | 27 Participants |
| Sex: Female, Male Female | 24 Participants | 46 Participants | 22 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 27 |
| other Total, other adverse events | 19 / 28 | 22 / 27 |
| serious Total, serious adverse events | 0 / 28 | 1 / 27 |
Outcome results
Primary
Change From Baseline to Week 18 in Sleep Metabolic Rate (SMR)
SMR was measured using whole-room indirect calorimetry (respiratory chamber). Change from Baseline to Week 18 in SMR was evaluated. Least square (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline, Treatment, Change from Baseline to Week 18 in Fat-Free Mass, Change from baseline to Week 18 in Fat Mass and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and had evaluable data for SMR.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Sleep Metabolic Rate (SMR) | -154.36 kilocalories per day (kcal/day) | Standard Error 19.69 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Sleep Metabolic Rate (SMR) | -134.68 kilocalories per day (kcal/day) | Standard Error 21.62 |
p-value: 0.573395% CI: [-50.36, 89.72]ANCOVA
Secondary
Change From Baseline to Week 18 in 24-hour Energy Expenditure (EE)
24 hour energy expenditure was measured in a respiratory chamber. LS mean was determined by ANCOVA model with Baseline, Treatment, Change from Baseline to Week 18 in Fat-Free Mass, Change from baseline to Week 18 in Fat Mass and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for 24-hour EE.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in 24-hour Energy Expenditure (EE) | -296.85 kcal/day | Standard Error 27.67 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in 24-hour Energy Expenditure (EE) | -300.07 kcal/day | Standard Error 30.44 |
p-value: 0.948195% CI: [-102.65, 96.2]ANCOVA
Secondary
Change From Baseline to Week 18 in 24 Hour Respiratory Quotient (RQ)
Respiratory quotient was calculated as the ratio of carbon dioxide production to oxygen consumption as measured in a metabolic chamber for 24 continuous hours. Ratio of total carbon dioxide production (VCO2)/total oxygen consumption (VO2), from baseline to Week 18 was evaluated. 24-hour RQ = total VCO2 \[Liter/24hour\] / total VO2 \[Liter/24hour\]. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for 24-hour RQ.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in 24 Hour Respiratory Quotient (RQ) | 0.005 Ratio | Standard Error 0.005 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in 24 Hour Respiratory Quotient (RQ) | -0.030 Ratio | Standard Error 0.006 |
p-value: <0.000195% CI: [-0.051, -0.018]ANCOVA
Secondary
Change From Baseline to Week 18 in Body Fat-Free Mass
Change from baseline to Week 18 in body fat free mass is presented. Body fat free mass was measured using dual energy X-ray absorptiometry (DXA) measurements. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for body fat-free mass.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Body Fat-Free Mass | -1.64 kg | Standard Error 0.36 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Body Fat-Free Mass | -5.73 kg | Standard Error 0.36 |
p-value: <0.000195% CI: [-5.12, -3.05]Mixed Models Analysis
Secondary
Change From Baseline to Week 18 in Body Fat Mass
Change from baseline to Week 18 in body fat mass is presented. Body fat mass was measured using DXA measurements. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for body fat mass.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Body Fat Mass | -6.75 kg | Standard Error 0.65 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Body Fat Mass | -11.83 kg | Standard Error 0.65 |
p-value: <0.000195% CI: [-6.93, -3.22]ANCOVA
Secondary
Change From Baseline to Week 18 in Body Weight (BW)
Change from baseline in BW through Week 18 in participants were presented. LS mean was determined by mixed measures repeated model (MMRM) model with Baseline, Treatment, Time, Treatment\*Time, Participant and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for body weight.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Body Weight (BW) | -8.26 kilogram (kg) | Standard Error 0.9 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Body Weight (BW) | -16.73 kilogram (kg) | Standard Error 0.92 |
p-value: <0.000195% CI: [-11.04, -5.9]Mixed Models Analysis
Secondary
Change From Baseline to Week 18 in Duration of Periods With RQ<0.80
RQ\<0.80 is defined as the cut point for high lipid oxidation of RQ; lipid oxidation will be calculated and corrected for protein oxidation; the total number of minutes with RQ \<0.80, termed lipid oxidation duration, during each 23-hour measurement period will be recorded; protein oxidation will be determined from urine nitrogen that will be collected during 2 periods for each calorimeter day. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for duration of periods with RQ\<0.80.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Duration of Periods With RQ<0.80 | 2.55 minute | Standard Error 43.97 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Duration of Periods With RQ<0.80 | 254.44 minute | Standard Error 47.14 |
p-value: 0.000495% CI: [119.09, 384.69]ANCOVA
Secondary
Change From Baseline to Week 18 in Fasting Insulin Resistance
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is a test that uses a simultaneous fasting blood glucose test and fasting insulin test to accurately estimate the degree of insulin resistance (IR) and β-cell function (the cells of the pancreas that produce insulin). HOMA-IR= \[Fasting glucose (mmol/L) x (fasting insulin (picomoles per liter {pmol/L})/6)\] / 22.5. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18 during standardized mixed meal tolerance test
Population: All randomized participants who received at least one dose of study drug and who had evaluable HOMA-IR data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Fasting Insulin Resistance | -0.37 index | Standard Error 0.12 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Fasting Insulin Resistance | -0.34 index | Standard Error 0.14 |
p-value: 0.876295% CI: [-0.34, 0.4]ANCOVA
Secondary
Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation
Change from Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation is presented. * Protein Oxidation = 6.25\*\[urinary nitrogen\] * Fat Oxidation = 1.689\*\[total oxygen consumption (VO2)\] - 1.689\*\[total carbon dioxide production (VCO2)\] - 0.324\*\[protein oxidation\] * Carbohydrate Oxidation = 4.113\*\[VCO2\] - 2.907\*\[VO2\] - 0.375\*\[protein oxidation\]. Adjusted oxidation is calculated using the formula, Adjusted oxidation rate (g/day) = oxidation rate (g/day) / 24-hour Energy Expenditure) x 1000 (kcal/day). LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for fat, protein, and carbohydrate oxidation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation | Adjusted protein oxidation | -0.14 gram/day | Standard Error 1.23 |
| Placebo | Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation | Adjusted fat oxidation | -1.64 gram/day | Standard Error 2.15 |
| Placebo | Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation | Adjusted carbohydrate oxidation | 4.23 gram/day | Standard Error 4.24 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation | Adjusted protein oxidation | -7.00 gram/day | Standard Error 1.32 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation | Adjusted fat oxidation | 12.83 gram/day | Standard Error 2.3 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Fat, Protein, and Carbohydrate Oxidation | Adjusted carbohydrate oxidation | -22.42 gram/day | Standard Error 4.54 |
Comparison: For Adjusted protein oxidationp-value: 0.000595% CI: [-10.51, -3.22]ANCOVA
Comparison: For Adjusted fat oxidationp-value: <0.000195% CI: [8.02, 20.93]ANCOVA
Comparison: Adjusted carbohydrate oxidationp-value: 0.000195% CI: [-39.46, -13.83]ANCOVA
Secondary
Change From Baseline to Week 18 in Food Intake During Ad Libitum Meal
Ad libitum lunch and dinner were provided. The sum of the caloric breakdown (carbohydrates, protein, and fats) was calculated from the respective nutritional information of the food items. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and had evaluable data for food Intake during ad libitum meal.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Food Intake During Ad Libitum Meal | -58.57 kilocalories (kcal) | Standard Error 82.29 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Food Intake During Ad Libitum Meal | -914.51 kilocalories (kcal) | Standard Error 82.29 |
p-value: <0.000195% CI: [-1090.87, -621.02]ANCOVA
Secondary
Change From Baseline to Week 18 in Hemoglobin A1c (HbA1c)
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was determined by ANCOVA model with Baseline, Treatment, Time, Treatment\*Time, Participant and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and had evaluable data for HbA1c.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Hemoglobin A1c (HbA1c) | -0.04 percentage of glycosylated hemoglobin | Standard Error 0.04 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Hemoglobin A1c (HbA1c) | -0.40 percentage of glycosylated hemoglobin | Standard Error 0.04 |
p-value: <0.000195% CI: [-0.48, -0.23]ANCOVA
Secondary
Change From Baseline to Week 18 in Lipid Metabolism Parameters
Change in Lipid Metabolism Parameters from baseline (week 0) to week 18 is evaluated. Triglyceride, Very low density lipoprotein (VLDL), High density lipoprotein (HDL) cholesterol and free fatty acids values were reported. Results below presents Area under the Curve (AUC) during standardized mixed-meal tolerance test (sMMTT). LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for lipid metabolism parameters.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Lipid Metabolism Parameters | Triglyceride | -0.69 millimole hour per liter (mmol.h/L) | Standard Error 0.27 |
| Placebo | Change From Baseline to Week 18 in Lipid Metabolism Parameters | VLDL cholesterol | -0.32 millimole hour per liter (mmol.h/L) | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 18 in Lipid Metabolism Parameters | HDL cholesterol | 0.20 millimole hour per liter (mmol.h/L) | Standard Error 0.18 |
| Placebo | Change From Baseline to Week 18 in Lipid Metabolism Parameters | Free fatty acid | -0.09 millimole hour per liter (mmol.h/L) | Standard Error 0.08 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Lipid Metabolism Parameters | Free fatty acid | 0.35 millimole hour per liter (mmol.h/L) | Standard Error 0.08 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Lipid Metabolism Parameters | Triglyceride | -2.52 millimole hour per liter (mmol.h/L) | Standard Error 0.27 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Lipid Metabolism Parameters | HDL cholesterol | -0.33 millimole hour per liter (mmol.h/L) | Standard Error 0.18 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Lipid Metabolism Parameters | VLDL cholesterol | -1.16 millimole hour per liter (mmol.h/L) | Standard Error 0.12 |
Comparison: For Triglyceridep-value: <0.000195% CI: [-2.6, -1.06]ANCOVA
Comparison: For VLDLp-value: <0.000195% CI: [-1.19, -0.48]ANCOVA
Comparison: For HDLp-value: 0.043695% CI: [-1.05, -0.02]ANCOVA
Comparison: For Free fatty acidp-value: 0.000295% CI: [0.23, 0.66]ANCOVA
Secondary
Change From Baseline to Week 18 in Percentage of Body Fat Mass
The total body fat mass was measured in kilograms (kg) using DXA scanning. Change from baseline to week 18 in percentage of body fat mass is reported. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for percentage of body fat mass.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Percentage of Body Fat Mass | -3.12 Percentage | Standard Error 0.36 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Percentage of Body Fat Mass | -4.26 Percentage | Standard Error 0.36 |
p-value: 0.030495% CI: [-2.16, -0.11]ANCOVA
Secondary
Change From Baseline to Week 18 in Postmeal Total Glucose AUC During sMMTT
Total AUC from time zero to 4 hours after start of the meal \[AUC0-4 hours\]) during sMMTT was evaluated. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and had evaluable data for postmeal total glucose AUC during sMMTT.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Postmeal Total Glucose AUC During sMMTT | -1.73 millimolar.hour per liter (mmol.h/L) | Standard Error 0.38 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Postmeal Total Glucose AUC During sMMTT | -3.00 millimolar.hour per liter (mmol.h/L) | Standard Error 0.38 |
p-value: 0.022295% CI: [-2.34, -0.19]ANCOVA
Secondary
Change From Baseline to Week 18 in Postprandial Insulin Sensitivity
Insulin sensitivity was measured from insulin and glucose levels obtained following standard meal challenge using a modification of the Matsuda index. This was calculated based on data obtained from a 75 g oral glucose tolerance test, as follows: 10,000 divided by the square root of {(fasting glucose X fasting insulin) (total area under the glucose response curve (AUC) 0-4hr)) X total insulin AUC(0-4hr )}. A Matsuda index of \<2.5 indicates whole body insulin resistance. A lower Matsuda Index indicates the worst disease state. An increase in the Matsuda Index indicates an improvement in insulin sensitivity (best). A positive change from Baseline indicates improvement and a negative change from Baseline indicates a worsening. Stumvoll and oral glucose insulin sensitivity indexes were also used for measuring the insulin Sensitivity. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and had evaluable data for matsuda index.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Postprandial Insulin Sensitivity | 1.43 index | Standard Deviation 0.94 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Postprandial Insulin Sensitivity | 4.92 index | Standard Deviation 0.94 |
p-value: 0.012695% CI: [0.79, 6.19]ANCOVA
Secondary
Change From Baseline to Week 18 in Sleep RQ
Sleep RQ is defined as the ratio of VCO2 to VO2 during sleep time points. Change from baseline to Week 18 in sleep RQ is presented. LS mean was determined by ANCOVA model with Baseline, Treatment and Random Error as variables.
Time frame: Baseline, Week 18
Population: All randomized participants who received at least one dose of study drug and who had evaluable data for sleep RQ.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 18 in Sleep RQ | -0.001 ratio | Standard Error 0.006 |
| 15 mg Tirzepatide | Change From Baseline to Week 18 in Sleep RQ | -0,028 ratio | Standard Error 0.006 |
p-value: 0.003195% CI: [-0.045, -0.01]ANCOVA