A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight

Phase 3

Completed

• Conditions: Overweight; Type 2 Diabetes; Obesity
• Interventions: Other: Placebo; Drug: Tirzepatide

• Registration Number: NCT04657003
• Lead Sponsor: Eli Lilly and Company

Brief Summary

This is a study of tirzepatide in participants with type 2 diabetes who have obesity or are overweight. The main purpose is to learn more about how tirzepatide affects body weight. The study will last 79 weeks (22 visits).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-01
• Study First Submitted QC: 2020-12-01
• Study First Posted: 2020-12-07
• Study Start: 2021-03-29
• Primary Completion: 2023-03-16
• Study Completion: 2023-04-10
• Status Verified: 2024-03
• Results First Submitted: 2024-03-08
• Results First Submitted QC: 2024-03-08
• Last Update Submitted: 2024-03-08
• Results First Posted: 2024-04-08
• Last Update Posted: 2024-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 938

Inclusion Criteria

• Have Type 2 Diabetes (T2DM) with HbA1c ≥7% to ≤10% at screening, on stable therapy for the last 3 months prior to screening. T2DM may be treated with diet/exercise alone or any oral glycemic-lowering agent (as per local labeling) EXCEPT dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon like peptide-1 receptor agonists (GLP-1 RAs)
• Have a BMI of ≥27 kg/m²
• Are overweight or have obesity
• Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight
• Are at least 18 years of age and age of majority per local laws and regulations

Exclusion Criteria

• Have Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma or any other types of diabetes except T2DM
• Have at least 2 confirmed fasting self-monitoring blood glucose (SMBG) values >270 mg/dL(on 2 nonconsecutive days) prior to Visit 3
• Have proliferative diabetic retinopathy OR diabetic macular edema OR non-proliferative diabetic retinopathy that requires acute treatment
• Have self-reported change in body weight >5kg within 3 months prior to screening
• Have had a history of chronic or acute pancreatitis
• 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
• 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	Placebo administered SC QW
10 milligrams (mg) Tirzepatide	Tirzepatide	10 mg Tirzepatide administered subcutaneously (SC) once weekly (QW)
15 mg Tirzepatide	Tirzepatide	15 mg Tirzepatide administered SC QW

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Body Weight	Baseline, Week 72	Least Squares Mean (LSMean) calculated using Mixed Model Repeated Measures (MMRM) model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of Antihyperglycemic Medication (AHM) Used at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants Who Achieve ≥5% Body Weight Reduction From Baseline	Week 72	Percentage of participants who achieve ≥5% body weight reduction from baseline

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieve ≥15% Body Weight Reduction From Baseline	Week 72	Percentage of participants who achieve ≥15% body weight reduction from baseline
Change From Baseline in Fasting Glucose	Baseline, Week 72	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Waist Circumference	Baseline, Week 72	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Baseline, Week 72	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Percent Change From Baseline in Non-High Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Baseline, Week 72	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Baseline, Week 72	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Percentage of Participants Who Achieve ≥10% Body Weight Reduction From Baseline	Week 72	Percentage of participants who achieve ≥10% body weight reduction from baseline
Change From Baseline in Absolute Body Weight	Baseline, Week 72	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants Who Achieve HbA1c ≤6.5%	Week 72	Percentage of participants who achieve HbA1c ≤6.5%
Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of 10 mg and 15 mg Tirzepatide)	Baseline, Week 72	LSMean was calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Short Form 36 Health Survey Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score	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.
Change From Baseline in Body Mass Index (BMI)	Baseline, Week 72	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Baseline, Week 72	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Percentage of Participants Who Achieve ≥20% Body Weight Reduction From Baseline	Week 72	Percentage of participants who achieve ≥20% body weight reduction from baseline
Change From Baseline in Hemoglobin A1c (HbA1c)	Baseline, Week 72	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants Who Achieve HbA1c <7%	Week 72	Percentage of participants who achieve HbA1c \<7%
Percentage of Participants Who Achieve HbA1c <5.7%	Week 72	Percentage of participants who achieve HbA1c \<5.7%
Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Baseline, Week 72	Results are reported as model-based estimates and standard error (SE) from MMRM analysis using log transformation.
Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Baseline, Week 72	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Percent Change From Baseline in Free Fatty Acids (Pooled Doses of 10 mg and 15 mg Tirzepatide)	Baseline, Week 72	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL Lite-CT) Physical Function Composite Score	Baseline, Week 72	The IWQOL-Lite-CT is a 20-item, obesity-specific patient reported outcome (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.
Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of 10 mg and 15 mg Tirzepatide)	Baseline, Week 72	LSMean was calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percent Change From Baseline in Fasting Insulin	Baseline, Week 72	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.
Population Pharmacokinetics (PopPK): Steady State Area Under the Concentration Curve (AUC) of Tirzepatide	Week 8, 16, 36: 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose	Each participant was 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. The steady state AUC was evaluated using Population PK modeling.

Trial Locations

Locations (75)

University of Alabama - Department of Nutrition Sciences; 🇺🇸 Birmingham, Alabama, United States

KLR Business Group, Inc. dba Arkansas Clinical Research; 🇺🇸 Little Rock, Arkansas, United States

Velocity Clinical Research, Huntington Park; 🇺🇸 Huntington Park, California, United States

Velocity Clinical Research, Westlake; 🇺🇸 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

ALL Medical Research, LLC; 🇺🇸 Cooper City, Florida, United States

Northeast Research Institute (NERI); 🇺🇸 Fleming Island, Florida, United States

New Horizon Research Center; 🇺🇸 Miami, Florida, United States

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