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

Eli Lilly and Company938 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

938

Conditions

Type 2 Diabetes Overweight Obesity

Interventions

TirzepatideDRUG

Administered SC

PlaceboOTHER

Administered SC

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (75)

Outcomes

Primary Outcomes

Percent Change From Baseline in Body Weight

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).

Time frame: Baseline, Week 72

Percentage of Participants Who Achieve ≥5% Body Weight Reduction From Baseline

Percentage of participants who achieve ≥5% body weight reduction from baseline

Time frame: Week 72

Secondary Outcomes

Percentage of Participants Who Achieve ≥10% Body Weight Reduction From Baseline

Percentage of participants who achieve ≥10% body weight reduction from baseline

Time frame: Week 72

Percentage of Participants Who Achieve ≥15% Body Weight Reduction From Baseline

Percentage of participants who achieve ≥15% body weight reduction from baseline

Time frame: Week 72

Percentage of Participants Who Achieve ≥20% Body Weight Reduction From Baseline

Percentage of participants who achieve ≥20% body weight reduction from baseline

Time frame: Week 72

Change From Baseline in Absolute Body Weight

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).

Time frame: Baseline, Week 72

Change From Baseline in Body Mass Index (BMI)

Data from ClinicalTrials.gov

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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

...and 65 more locations

Time frame: Baseline, Week 72

Change From Baseline in Hemoglobin A1c (HbA1c)

Time frame: Baseline, Week 72

Percentage of Participants Who Achieve HbA1c <7%

Percentage of participants who achieve HbA1c \<7%

Time frame: Week 72

Percentage of Participants Who Achieve HbA1c ≤6.5%

Percentage of participants who achieve HbA1c ≤6.5%

Time frame: Week 72

Percentage of Participants Who Achieve HbA1c <5.7%

Percentage of participants who achieve HbA1c \<5.7%

Time frame: Week 72

Change From Baseline in Fasting Glucose

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).

Time frame: Baseline, Week 72

Change From Baseline in Waist Circumference

Time frame: Baseline, Week 72

Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)

Results are reported as model-based estimates and standard error (SE) from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)

Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)

Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)

Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 10 mg and 15 mg)

Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Percent Change From Baseline in Non-High Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)

Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Percent Change From Baseline in Free Fatty Acids (Pooled Doses of 10 mg and 15 mg Tirzepatide)

Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of 10 mg and 15 mg Tirzepatide)

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).

Time frame: Baseline, Week 72

Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of 10 mg and 15 mg Tirzepatide)

Time frame: Baseline, Week 72

Percent Change From Baseline in Fasting Insulin

Results are reported as model-based estimates and SE from MMRM analysis using log transformation.

Time frame: Baseline, Week 72

Change From Baseline in Short Form 36 Health Survey Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score

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.

Time frame: Baseline, Week 72

Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL Lite-CT) Physical Function Composite Score

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.

Time frame: Baseline, Week 72

Population Pharmacokinetics (PopPK): Steady State Area Under the Concentration Curve (AUC) of Tirzepatide

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.

Time frame: Week 8, 16, 36: 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose