A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight

Phase 3

Completed

Conditions: Obesity
Overweight

Interventions: Drug: Placebo
Drug: Tirzepatide

Registration Number: NCT04184622

Lead Sponsor: Eli Lilly and Company

Brief Summary: This is a study of tirzepatide in participants with overweight and obesity. The main purpose is to learn more about how tirzepatide affects body weight. The study has two phases: A main phase and an extension phase. The main phase of the study will last 72 weeks. Participants with prediabetes will continue in the extension for another 2 years.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2539

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	* Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received once weekly (QW) subcutaneous (SC) doses of a matching placebo, administered over a period of 72 weeks. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the placebo dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.
5 mg Tirzepatide	Tirzepatide	* Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 milligrams (mg) and increasing by 2.5 mg every 4 weeks until reaching a dose of 5 mg, which was then maintained up to week 72. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the 5 mg tirzepatide dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.
10 mg Tirzepatide	Tirzepatide	* Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks until reaching a dose of 10 mg, which was then maintained up to week 72. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the 10 mg tirzepatide dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.
15 mg Tirzepatide	Tirzepatide	* Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received QW SC doses of tirzepatide, starting at 2.5 mg and increasing by 2.5 mg every 4 weeks until reaching a dose of 15 mg, which was then maintained up to week 72. * Additional Treatment Period (Week 72-Week 176): At week 72, only participants who had prediabetes at the time of randomization and had completed the primary treatment period continued receiving the 15 mg tirzepatide dose SC QW until week 176. * Safety Follow-up Period: Participants who had completed or discontinued the primary treatment period were followed for safety for 4 weeks (weeks 72 - week 76), and those who had completed or discontinued the additional treatment period (prediabetes at randomization) were followed for 17 weeks (week 176 - week 193). No treatment was administered during this period.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Body Weight (Primary Treatment Period)	Baseline, Week 72	Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary Treatment Period)	Week 72	Percentage of participants who achieve greater than or equal to( ≥) 5% body weight reduction.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Body Weight (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 20	LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Percentage of Participants Who Achieve ≥10% Body Weight Reduction (Primary Treatment Period)	Week 72	Percentage of Participants who Achieve ≥10% Body Weight Reduction
Percentage of Participants Who Achieve ≥15% Body Weight Reduction (Primary Treatment Period)	Week 72	Percentage of participants who achieve ≥15% body weight reduction.
Percentage of Participants Who Achieve ≥20% Body Weight Reduction (Primary Treatment Period)	Week 72	Percentage of participants who achieve ≥20% body weight reduction.
Change From Baseline in Waist Circumference (Primary Treatment Period)	Baseline, Week 72	LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Change From Baseline in Short Form Survey-36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score at Week 72 (Pooled Doses of Tirzepatide 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" while the remaining domains assess functioning "in the past week." Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.
Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	Percent change from baseline in triglycerides are reported as model-based estimate and Standard Error (SE) from MMRM analysis using log transformation.
Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol at Week 72 (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Percent Change From Baseline in Fasting Insulin (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	Fasting Insulin is a test used to measure the amount of insulin in the body. Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)	Baseline, Week 176	LS Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, treatment, time, treatment\*time (Type III sum of squares) in the model.
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 176 (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)	Baseline through Week 176	The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.
Percentage of Participants With Onset of Type 2 Diabetes From Baseline to Week 193 (Primary and Additional Treatment Periods + Safety Follow-up Period: Participants With Prediabetes at Randomization)	Baseline through Week 193	The percentage of participants with onset of Type 2 diabetes mellitus (T2DM), evaluated as time to onset of T2DM among those who had pre-diabetes at randomization, was reported. Time to onset of Type 2 diabetes mellitus was defined as the duration from the date of randomization to the adjudication committee-confirmed date of incident diabetes. Participants who did not experience the event were censored.
Change From Baseline in Body Mass Index (BMI) - Primary Treatment Period	Baseline, Week 72	LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Change From Baseline in Hemoglobin A1c (HbA1c) - Primary Treatment Period	Baseline, Week 72	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Change From Baseline in Fasting Glucose (Primary Treatment Period)	Baseline, Week 72	LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Percent Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Percent Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Percent Change From Baseline in Free Fatty Acids (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	Results are reported as model-based estimate and SE from MMRM analysis using log transformation.
Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) - Primary Treatment Period	Baseline, Week 72	LS Mean was calculated using MMRM with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.
Percentage of Participants Who Achieve ≥5% Body Weight Reduction (Primary and Additional Treatment Periods : Participants With Prediabetes at Randomization)	Week 176	Percentage of Participants Who Achieve ≥5% Body Weight Reduction.
Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score at Week 72 (Primary Treatment Period)	Baseline, Week 72	The IWQOL-Lite-CT is a 20-item, obesity-specific patient-reported outcomes (PRO) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life.
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide (Primary Treatment Period)	Week 8, 16, and 36, at 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose	PK: Steady State AUC of Tirzepatide. each participant will be assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose.

Trial Locations

Locations (117): Cahaba Research
🇺🇸
Pelham, Alabama, United States
Perseverance Research Center
🇺🇸
Scottsdale, Arizona, United States
John Muir Physician Network Clinical Research Center
🇺🇸
Concord, California, United States
Valley Research
🇺🇸
Fresno, California, United States
National Research Institute - Wilshire
🇺🇸
Los Angeles, California, United States
Catalina Research Institute, LLC
🇺🇸
Montclair, California, United States
Encompass Clinical Research
🇺🇸
Spring Valley, California, United States
University Clinical Investigators, Inc.
🇺🇸
Tustin, California, United States
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
Chase Medical Research, LLC
🇺🇸
Waterbury, Connecticut, United States
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Cahaba Research
🇺🇸Pelham, Alabama, United States