Clincosm LogoSign in Get a demo

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT03311724
Collaborator
(none)
111
Enrollment
13
Locations
4
Arms
6.1
Actual Duration (Months)
8.5
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy of tirzepatide in participants with type 2 diabetes.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
111 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Double-Blind, Placebo-Controlled, 3-Month Trial of LY3298176 Versus Placebo in Patients With Type 2 Diabetes Mellitus
Actual Study Start Date :
Oct 19, 2017
Actual Primary Completion Date :
Apr 24, 2018
Actual Study Completion Date :
Apr 24, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: 4,8,12mg Tirzepatide

Participants received Tirzepatide by subcutaneous (SC) injection in three dose escalations starting with 4 milligrams (mg) for four weeks followed by 8mg for four weeks followed by 12mg for four weeks.

Drug: Tirzepatide
Administered SC
Other Names:
  • LY3298176

    		•
    Experimental: 2.5,5,10,15mg Tirzepatide

    Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks.

    Drug: Tirzepatide
    Administered SC
    Other Names:
  • LY3298176

    		•
    Experimental: 2.5,7.5,15mg Tirzepatide

    Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.

    Drug: Tirzepatide
    Administered SC
    Other Names:
  • LY3298176

    		•
    Placebo Comparator: Placebo

    Placebo administered by SC injection.

    Drug: Placebo
    Administered SC

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Haemoglobin A1c (HbA1c) [Baseline, 3 Months]

      Least squares (LS) mean was calculated using mixed model repeated measures model (MMRM) with baseline + baseline BMI group + baseline metformin flag + treatment + time + treatment*time as fixed factors.

    Secondary Outcome Measures

    1. Percentage of Participants Achieving HbA1c Target of <7.0% [3 Months]

      Percentage of participants achieving HbA1c target of < (less than) 7.0%.

    2. Change From Baseline in Fasting Blood Glucose (FBG) [Baseline, 3 Months]

      LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors.

    3. Change From Baseline in Body Weight [Baseline, 3 Months]

      LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors.

    4. Change From Baseline in Waist Circumference [Baseline, 3 Months]

      LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors.

    5. Number of Participants With Anti Drug Antibodies [Baseline through 3 Months]

      Number of participants with anti drug antibodies.

    6. Number of Episodes of Total Hypoglycemia Episodes [Baseline through 3 Months]

      Number of episodes of total hypoglycemia episodes with plasma glucose <= ( less than or equal to) 54 mg/dL.

    7. Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide [Week 4, 8 12: Pre-dose]

      Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Have type 2 diabetes (T2DM) for ≥6 months according to the Criteria for Diagnosing Type 2 Diabetes Mellitus (American Diabetes Association 2017).

    • Have HbA1c of 7.0% to 10.5%, inclusive, as assessed by the central laboratory.

    • If on metformin, have been treated with stable doses of metformin for at least 3 months.

    • Have a body mass index (BMI) between 23 and 45 (Inclusive) kilograms per square meter.

    Exclusion Criteria:

    • Have type 1 diabetes (T1D).

    • Have used any glucose-lowering medication other than metformin within 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past 12 months.

    • Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke).

    • Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level

    2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial.

    • Have had chronic or acute pancreatitis any time prior to study entry.

    • Have an estimated glomerular filtration rate (eGFR) <45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation.

    • Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry.

    • Have any condition that is a contraindication for use of the GLP-1 RA class (per country-specific labels) at study entry or develop such condition between study entry and randomization.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Valley Research Fresno California United States 93720
    2 National Research Institute Los Angeles California United States 90057
    3 Catalina Research Institute, LLC Montclair California United States 91763
    4 University Clinical Investigators, Inc. Tustin California United States 92780
    5 Chase Medical Research, LLC Waterbury Connecticut United States 06708
    6 Suncoast Research Group, LLC Miami Florida United States 33135
    7 Solaris Clinical Research Meridian Idaho United States 83646
    8 Cotton O'Neil Diabetes and Endocrinology Center Topeka Kansas United States 66606
    9 Clinical Research Professionals Saint Louis Missouri United States 63141
    10 Aventiv Research Columbus Ohio United States 43213
    11 New Phase Research & Development Knoxville Tennessee United States 37909
    12 Dallas Diabetes Endocrine Center Dallas Texas United States 75230
    13 Consano Clinical Research Shavano Park Texas United States 78231

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03311724
    Other Study ID Numbers:
    • 16860
    • I8F-MC-GPGF
    First Posted:
    Oct 17, 2017
    Last Update Posted:
    May 19, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Tirzepatide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Participants received Placebo by subcutaneous (SC) injection. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Period Title: Overall Study
    STARTED 26 29 28 28
    Received At Least One Dose of Study Drug 26 29 28 28
    Completed Treatment 20 27 22 26
    COMPLETED 23 28 26 27
    NOT COMPLETED 3 1 2 1

    Baseline Characteristics

    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide Total
    Arm/Group Description Placebo administered by SC injection. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks. Total of all reporting groups
    Overall Participants 26 29 28 28 111
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.0
    (10.13)
    61.2
    (7.56)
    55.5
    (8.54)
    56.6
    (9.21)
    57.4
    (9.06)
    Sex: Female, Male (Count of Participants)
    Female
    14
    53.8%
    14
    48.3%
    12
    42.9%
    5
    17.9%
    45
    40.5%
    Male
    12
    46.2%
    15
    51.7%
    16
    57.1%
    23
    82.1%
    66
    59.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    16
    61.5%
    15
    51.7%
    14
    50%
    14
    50%
    59
    53.2%
    Not Hispanic or Latino
    10
    38.5%
    14
    48.3%
    14
    50%
    14
    50%
    52
    46.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    2
    6.9%
    1
    3.6%
    0
    0%
    3
    2.7%
    Asian
    0
    0%
    1
    3.4%
    2
    7.1%
    1
    3.6%
    4
    3.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    3.8%
    7
    24.1%
    5
    17.9%
    2
    7.1%
    15
    13.5%
    White
    25
    96.2%
    19
    65.5%
    20
    71.4%
    23
    82.1%
    87
    78.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    2
    7.1%
    2
    1.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    26
    100%
    29
    100%
    28
    100%
    28
    100%
    111
    100%
    Hemoglobin A1c (HbA1c) (Percentage of HbA1C) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Percentage of HbA1C]
    8.23
    (1.22)
    8.35
    (0.897)
    8.48
    (1.171)
    8.35
    (1.12)
    8.35
    (1.094)
    Fasting Blood Glucose (FBG) (millimoles per liter (mmol/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimoles per liter (mmol/L)]
    9.68
    (3.44)
    9.76
    (3.03)
    10.40
    (4.04)
    10.67
    (4.22)
    10.13
    (3.69)
    Body Weight (kilogram (kg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilogram (kg)]
    89.58
    (23.69)
    87.98
    (17.35)
    88.74
    (18.21)
    89.59
    (16.91)
    88.95
    (18.87)
    Waist Circumference (centimeter (cm)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [centimeter (cm)]
    109.09
    (15.38)
    107.65
    (12.22)
    107.02
    (12.64)
    105.10
    (12.19)
    107.19
    (13.02)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Haemoglobin A1c (HbA1c)
    Description Least squares (LS) mean was calculated using mixed model repeated measures model (MMRM) with baseline + baseline BMI group + baseline metformin flag + treatment + time + treatment*time as fixed factors.
    Time Frame Baseline, 3 Months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug and had baseline and at least one post baseline data. Participants who discontinued study drug or initiated rescue drug were excluded.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 20 27 23 26
    Least Squares Mean (Standard Error) [Percentage of HbA1C]
    0.2
    (0.21)
    -1.7
    (0.19)
    -2.0
    (0.20)
    -1.8
    (0.19)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 4, 8 and 12mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95%
    -2.5 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 5, 10, and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -2.8 to -1.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 7.5 and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -2.5 to -1.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants Achieving HbA1c Target of <7.0%
    Description Percentage of participants achieving HbA1c target of < (less than) 7.0%.
    Time Frame 3 Months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug and had baseline and at least one post baseline data. Participants who discontinued study drug or initiated rescue drug were excluded.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 20 27 23 26
    Number [percentage of participants]
    10
    38.5%
    74.1
    255.5%
    87
    310.7%
    84.6
    302.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 4, 8 and 12mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 56.54
    Confidence Interval (2-Sided) 95%
    9.43 to 338.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 5, 10, and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 183.48
    Confidence Interval (2-Sided) 95%
    22.0 to 999
    Parameter Dispersion Type:
    Value:
    Estimation Comments Maximum confidential interval is ">999"
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 7.5 and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 157.54
    Confidence Interval (2-Sided) 95%
    21.63 to 999
    Parameter Dispersion Type:
    Value:
    Estimation Comments Maximum confidential interval is ">999"
    3. Secondary Outcome
    Title Change From Baseline in Fasting Blood Glucose (FBG)
    Description LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors.
    Time Frame Baseline, 3 Months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug and had baseline and at least one post baseline data. Participants who discontinued study drug or initiated rescue drug were excluded.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 20 27 23 25
    Least Squares Mean (Standard Error) [milligrams per deciliter (mg/dL)]
    -12.3
    (9.27)
    -60.7
    (8.21)
    -70.2
    (8.72)
    -74.2
    (8.67)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 4, 8 and 12mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -48.5
    Confidence Interval (2-Sided) 95%
    -70.6 to -26.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 5, 10, and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -58.0
    Confidence Interval (2-Sided) 95%
    -80.7 to -35.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 7.5 and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -61.9
    Confidence Interval (2-Sided) 95%
    -84.6 to -39.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in Body Weight
    Description LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors.
    Time Frame Baseline, 3 Months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug and had baseline and at least one post baseline data. Participants who discontinued study drug or initiated rescue drug were excluded.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 20 27 23 26
    Least Squares Mean (Standard Error) [kilogram (kg)]
    -0.5
    (0.86)
    -5.3
    (0.78)
    -5.5
    (0.80)
    -5.7
    (0.79)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 4, 8 and 12mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.8
    Confidence Interval (2-Sided) 95%
    -7.1 to -2.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 5, 10, and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -5.0
    Confidence Interval (2-Sided) 95%
    -7.2 to -2.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 7.5 and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -5.2
    Confidence Interval (2-Sided) 95%
    -7.5 to -2.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in Waist Circumference
    Description LSMean was calculated using MMRM model with baseline + baseline HbA1C group + baseline BMI group + baseline Metformin flag + treatment + time + treatment*time as fixed factors.
    Time Frame Baseline, 3 Months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug and had baseline and at least one post baseline data. Participants who discontinued study drug or initiated rescue drug were excluded.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 20 27 23 26
    Least Squares Mean (Standard Error) [centimeter (cm)]
    -2.5
    (1.01)
    -4.8
    (0.90)
    -4.9
    (0.94)
    -4.9
    (0.93)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, 4, 8 and 12mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.075
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.2
    Confidence Interval (2-Sided) 95%
    -4.7 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 5, 10, and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.065
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -4.9 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, 2.5, 7.5 and 15mg Tirzepatide
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.065
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.4
    Confidence Interval (2-Sided) 95%
    -4.9 to 0.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Number of Participants With Anti Drug Antibodies
    Description Number of participants with anti drug antibodies.
    Time Frame Baseline through 3 Months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 25 29 28 27
    Number [participants]
    0
    0%
    10
    34.5%
    8
    28.6%
    4
    14.3%
    7. Secondary Outcome
    Title Number of Episodes of Total Hypoglycemia Episodes
    Description Number of episodes of total hypoglycemia episodes with plasma glucose <= ( less than or equal to) 54 mg/dL.
    Time Frame Baseline through 3 Months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC. Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 26 29 28 28
    Number [Episodes]
    0
    0
    0
    1
    8. Secondary Outcome
    Title Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide
    Description Pharmacokinetics (PK): Average Trough Concentration (Conctrough) of Tirzepatide.
    Time Frame Week 4, 8 12: Pre-dose

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had evaluable PK samples.
    Arm/Group Title 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    Measure Participants 29 28 28
    Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]
    508
    (366)
    704
    (518)
    630
    (414)

    Adverse Events

    Time Frame Baseline through end of study (Up to 15 weeks).
    Adverse Event Reporting Description All randomized participants.
    Arm/Group Title Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Arm/Group Description Placebo administered SC Participants received Tirzepatide by SC injection in three dose escalations starting with 4mg for four weeks followed by 8mg for four weeks followed by 12mg for four weeks. Participants received Tirzepatide by SC injection in four dose escalations starting with 2.5mg for two weeks followed by 5mg for two weeks followed by 10mg for four weeks followed by 15mg for four weeks. Participants received Tirzepatide by SC injection in three dose escalations starting with 2.5mg for four weeks followed by 7.5mg for four weeks followed by 15mg for four weeks.
    All Cause Mortality
    Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/26 (0%) 0/29 (0%) 0/28 (0%) 0/28 (0%)
    Serious Adverse Events
    Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/26 (0%) 1/29 (3.4%) 0/28 (0%) 0/28 (0%)
    Gastrointestinal disorders
    Diarrhoea 0/26 (0%) 0 1/29 (3.4%) 1 0/28 (0%) 0 0/28 (0%) 0
    Investigations
    White blood cell count increased 0/26 (0%) 0 1/29 (3.4%) 1 0/28 (0%) 0 0/28 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo 4, 8 and 12mg Tirzepatide 2.5, 5, 10, and 15mg Tirzepatide 2.5, 7.5 and 15mg Tirzepatide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/26 (26.9%) 19/29 (65.5%) 18/28 (64.3%) 22/28 (78.6%)
    Gastrointestinal disorders
    Abdominal distension 0/26 (0%) 0 0/29 (0%) 0 3/28 (10.7%) 9 2/28 (7.1%) 2
    Abdominal pain 1/26 (3.8%) 1 1/29 (3.4%) 1 5/28 (17.9%) 5 1/28 (3.6%) 1
    Abdominal pain upper 0/26 (0%) 0 2/29 (6.9%) 3 1/28 (3.6%) 2 2/28 (7.1%) 4
    Constipation 0/26 (0%) 0 1/29 (3.4%) 1 3/28 (10.7%) 5 5/28 (17.9%) 5
    Diarrhoea 2/26 (7.7%) 2 9/29 (31%) 18 10/28 (35.7%) 19 9/28 (32.1%) 19
    Dyspepsia 0/26 (0%) 0 5/29 (17.2%) 7 3/28 (10.7%) 12 3/28 (10.7%) 3
    Eructation 0/26 (0%) 0 2/29 (6.9%) 3 0/28 (0%) 0 0/28 (0%) 0
    Flatulence 0/26 (0%) 0 1/29 (3.4%) 1 2/28 (7.1%) 3 2/28 (7.1%) 3
    Gastrooesophageal reflux disease 0/26 (0%) 0 2/29 (6.9%) 3 1/28 (3.6%) 1 2/28 (7.1%) 2
    Nausea 2/26 (7.7%) 2 7/29 (24.1%) 14 11/28 (39.3%) 18 10/28 (35.7%) 16
    Vomiting 1/26 (3.8%) 1 5/29 (17.2%) 6 5/28 (17.9%) 7 5/28 (17.9%) 7
    General disorders
    Fatigue 0/26 (0%) 0 1/29 (3.4%) 1 2/28 (7.1%) 2 0/28 (0%) 0
    Injection site reaction 0/26 (0%) 0 2/29 (6.9%) 3 2/28 (7.1%) 2 0/28 (0%) 0
    Infections and infestations
    Pharyngitis 2/26 (7.7%) 3 0/29 (0%) 0 0/28 (0%) 0 0/28 (0%) 0
    Upper respiratory tract infection 2/26 (7.7%) 2 2/29 (6.9%) 2 0/28 (0%) 0 0/28 (0%) 0
    Urinary tract infection 0/26 (0%) 0 0/29 (0%) 0 2/28 (7.1%) 2 0/28 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/26 (0%) 0 4/29 (13.8%) 4 6/28 (21.4%) 7 8/28 (28.6%) 20
    Musculoskeletal and connective tissue disorders
    Back pain 2/26 (7.7%) 2 1/29 (3.4%) 1 0/28 (0%) 0 1/28 (3.6%) 1
    Muscle spasms 1/26 (3.8%) 1 1/29 (3.4%) 1 0/28 (0%) 0 2/28 (7.1%) 2
    Osteoarthritis 0/26 (0%) 0 0/29 (0%) 0 2/28 (7.1%) 2 0/28 (0%) 0
    Nervous system disorders
    Dizziness 2/26 (7.7%) 2 0/29 (0%) 0 1/28 (3.6%) 1 3/28 (10.7%) 9
    Headache 2/26 (7.7%) 2 2/29 (6.9%) 5 6/28 (21.4%) 10 5/28 (17.9%) 27
    Respiratory, thoracic and mediastinal disorders
    Cough 1/26 (3.8%) 1 2/29 (6.9%) 3 2/28 (7.1%) 2 0/28 (0%) 0
    Sinus congestion 0/26 (0%) 0 2/29 (6.9%) 2 1/28 (3.6%) 1 1/28 (3.6%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email ClinicalTrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT03311724
    Other Study ID Numbers:
    • 16860
    • I8F-MC-GPGF
    First Posted:
    Oct 17, 2017
    Last Update Posted:
    May 19, 2021
    Last Verified:
    Apr 1, 2021