A Study to Measure Energy Expenditure and Food Intake in Participants With Obesity Using Tirzepatide

Phase 1

Completed

Conditions: Obesity

Interventions: Drug: Tirzepatide
Drug: Placebo

Registration Number: NCT04081337

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 55

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
15 Milligram (mg) Tirzepatide	Tirzepatide	Participants received 15 mg of tirzepatide QW by SC injection.
Placebo	Placebo	Participants received placebo once weekly (QW) by Subcutaneous (SC) injection.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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 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 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 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 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 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 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 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 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 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 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 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.