SURPASS-1: A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT03954834
Collaborator
(none)
478
53
4
16.9
9
0.5

Study Details

Study Description

Brief Summary

The goal for this study is to evaluate the efficacy and safety of tirzepatide versus placebo in participants with type 2 diabetes not under control with diet and exercise alone. The study will last approximately 47 weeks and may include about 15 visits.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
478 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-Controlled Trial Comparing the Efficacy and Safety of Three Tirzepatide Doses Versus Placebo in Patients With Type 2 Diabetes, Inadequately Controlled With Diet and Exercise Alone
Actual Study Start Date :
Jun 3, 2019
Actual Primary Completion Date :
Oct 5, 2020
Actual Study Completion Date :
Oct 28, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: 5 mg Tirzepatide

Participants received 5 milligrams (mg) of tirzepatide as subcutaneous injection once a week.

Drug: Tirzepatide
Administered SC
Other Names:
  • LY3298176
  • Experimental: 10 mg Tirzepatide

    Participants received 10mg of tirzepatide as subcutaneous injection once a week.

    Drug: Tirzepatide
    Administered SC
    Other Names:
  • LY3298176
  • Experimental: 15 mg Tirzepatide

    Participants received 15mg of tirzepatide as subcutaneous injection once a week.

    Drug: Tirzepatide
    Administered SC
    Other Names:
  • LY3298176
  • Placebo Comparator: Placebo

    Participants received placebo as subcutaneous injection once a week.

    Drug: Placebo
    Administered SC

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Hemoglobin A1c (HbA1c) [Baseline, Week 40]

      HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).

    Secondary Outcome Measures

    1. Change From Baseline in Body Weight [Baseline, Week 40]

      Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).

    2. Percentage of Participants With HbA1c Target Value of <7% [Week 40]

      Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

    3. Change From Baseline in Fasting Serum Glucose [Baseline, Week 40]

      Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).

    4. Percentage of Participants With HbA1c Target Value of <5.7% [Week 40]

      Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

    5. Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values [Baseline, Week 40]

      The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).

    6. Percentage of Participants Who Achieved Weight Loss ≥5% [Week 40]

      Percentage of Participants who Achieved Weight Loss ≥5%.

    7. Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia [Baseline through end of safety follow-up (up to week 44)]

      The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL) (<3.0 mmol/L] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable.

    8. Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide [Week 7, 15 and 23]

      Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Have been diagnosed with type 2 diabetes mellitus (T2DM).

    • Are naïve to diabetes injectable therapies and have not used any oral antihyperglycemic medications (OAMs) during the 3 months preceding screening.

    • Have HbA1c between ≥7.0% and ≤9.5%.

    • Be of stable weight (± 5%) for at least 3 months before screening.

    • Have a BMI ≥23 kilograms per meter squared (kg/m²) at screening.

    Exclusion Criteria:
    • Have type 1 diabetes mellitus.

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

    • Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring acute treatment.

    • Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.

    • Have an estimated glomerular filtration rate <30 mL/minute/1.73 m².

    • Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months.

    • Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2.

    • Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Research Institute Huntington Park California United States 90255
    2 National Research Institute Los Angeles California United States 90057
    3 Catalina Research Institute, LLC Montclair California United States 91763
    4 Valley Clinical Trials, Inc. Northridge California United States 91325
    5 National Research Institute Panorama City California United States 91402
    6 Southern California Dermatology Santa Ana California United States 92701
    7 Clinical Research of South Florida Coral Gables Florida United States 33134
    8 Encore Medical Research, LLC Hollywood Florida United States 33021
    9 Axcess Medical Research Loxahatchee Groves Florida United States 33470
    10 South Florida Wellness & Clinical Research Institute Margate Florida United States 33063
    11 Suncoast Research Group, LLC Miami Florida United States 33135
    12 Agile Clinical Research Trials Atlanta Georgia United States 30328
    13 Sky Clinical Research Network Atlanta Georgia United States 30331
    14 Cotton O'Neil Clinic Topeka Kansas United States 66606
    15 Clinical Research Professionals Chesterfield Missouri United States 63005
    16 StudyMetrix Research, LLC Saint Peters Missouri United States 63303
    17 Aventiv Research Columbus Ohio United States 43213
    18 Intend Research Norman Oklahoma United States 73069
    19 The Corvallis Clinic P.C. Corvallis Oregon United States 97330
    20 Heritage Valley Medical Group, Inc. Beaver Pennsylvania United States 15009
    21 Family Medical Associates Levittown Pennsylvania United States 19056
    22 Preferred Primary Care Physicians Pittsburgh Pennsylvania United States 15236
    23 Preferred Primary Care Physicians Uniontown Pennsylvania United States 15401
    24 Dallas Diabetes Endocrine Center Dallas Texas United States 75230
    25 Clinical Trials of Texas, Inc. San Antonio Texas United States 78229
    26 Consano Clinical Research Shavano Park Texas United States 78231
    27 Capital Clinical Research Center Olympia Washington United States 98502
    28 Rockwood Clinic Research Center Spokane Washington United States 99220
    29 Dr. Jivraj Mehta Smarak Health Foundation Ahmedabad Gujarat India 380007
    30 Bangalore Medical College and Research Institute Bangalore Karnataka India 560 002
    31 M S Ramaiah Medical College Hospital Bangalore Karnataka India 560054
    32 BSES Municipal General Hsptl Mumbai Maharashtra India 400058
    33 Ruby Hall Clinic and Grant Medical Foundation Pune Maharashtra India 411001
    34 Vijay Vallabh Hospital Virar Maharashtra India 401303
    35 Lifepoint Multispecialty Hsptl Wakad Pune India 411057
    36 Ramdevrao Hospital Hyderabad Telangana India 500072
    37 Gandhi Hospital Telangana India 500003
    38 Minamiakatsuka Clinic Mito Ibaraki Japan 311-4153
    39 Takai Naika Clinic Kamakura Kanagawa Japan 247-0056
    40 Tsuruma Kaneshiro Diabetes Clinic Yamato Kanagawa Japan 242-0004
    41 Yokohama Minoru Clinic Yokohama Kanagawa Japan 232-0064
    42 Takatsuki Red Cross Hospital Takatsuki Osaka Japan 569-1096
    43 Meiwa Hospital Chiyodaku Tokyo Japan 101 0041
    44 Tokyo-Eki Center-building Clinic Chuo-ku Tokyo Japan 103-0027
    45 Tokyo Center Clinic Chuo-ku Tokyo Japan 103-0028
    46 IHL Shinagawa East One Medical Clinic Minato-ku Tokyo Japan 108 0075
    47 Sato Naika Clinic Ota-ku Tokyo Japan 143-0015
    48 Hospital Universitario UANL Monterrey Nuevo León Mexico 64460
    49 Unidad Medica para la Salud Integral (UMSI) Monterrey Nuevo León Mexico 66465
    50 Centro de Estudios de Investigacion Metabolicos y Cardiovasc Madero Tamaulipas Mexico 89440
    51 Investigacion en Salud y Metabolismo S.C Chihuahua Mexico 31217
    52 Clinical Research Puerto Rico, Inc. San Juan Puerto Rico 00909
    53 GCM Medical Group PSC San Juan Puerto Rico 00917

    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:
    NCT03954834
    Other Study ID Numbers:
    • 17000
    • I8F-MC-GPGK
    First Posted:
    May 17, 2019
    Last Update Posted:
    Oct 20, 2021
    Last Verified:
    Oct 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
    Keywords provided by Eli Lilly and Company
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Period Title: Overall Study
    STARTED 121 121 121 115
    Received at Least One Dose of Study Drug 121 121 121 115
    COMPLETED 114 112 103 99
    NOT COMPLETED 7 9 18 16

    Baseline Characteristics

    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo Total
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week. Total of all reporting groups
    Overall Participants 121 121 121 115 478
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.10
    (11.88)
    55.80
    (10.35)
    52.90
    (12.34)
    53.60
    (12.79)
    54.10
    (11.88)
    Sex: Female, Male (Count of Participants)
    Female
    65
    53.7%
    49
    40.5%
    58
    47.9%
    59
    51.3%
    231
    48.3%
    Male
    56
    46.3%
    72
    59.5%
    63
    52.1%
    56
    48.7%
    247
    51.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    50
    41.3%
    54
    44.6%
    55
    45.5%
    48
    41.7%
    207
    43.3%
    Not Hispanic or Latino
    48
    39.7%
    49
    40.5%
    42
    34.7%
    45
    39.1%
    184
    38.5%
    Unknown or Not Reported
    23
    19%
    18
    14.9%
    24
    19.8%
    22
    19.1%
    87
    18.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    31
    25.6%
    31
    25.6%
    30
    24.8%
    26
    22.6%
    118
    24.7%
    Asian
    45
    37.2%
    43
    35.5%
    42
    34.7%
    38
    33%
    168
    35.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    7
    5.8%
    4
    3.3%
    6
    5%
    5
    4.3%
    22
    4.6%
    White
    38
    31.4%
    43
    35.5%
    43
    35.5%
    46
    40%
    170
    35.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    India
    18
    14.9%
    20
    16.5%
    18
    14.9%
    17
    14.8%
    73
    15.3%
    Japan
    23
    19%
    22
    18.2%
    23
    19%
    21
    18.3%
    89
    18.6%
    Mexico
    42
    34.7%
    40
    33.1%
    42
    34.7%
    40
    34.8%
    164
    34.3%
    Puerto Rico
    2
    1.7%
    4
    3.3%
    5
    4.1%
    1
    0.9%
    12
    2.5%
    United States
    36
    29.8%
    35
    28.9%
    33
    27.3%
    36
    31.3%
    140
    29.3%
    Hemoglobin A1c (Percentage of HbA1c) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Percentage of HbA1c]
    7.97
    (0.841)
    7.90
    (0.78)
    7.85
    (1.02)
    8.05
    (0.80)
    7.94
    (0.87)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Hemoglobin A1c (HbA1c)
    Description HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 121 118 116 112
    Least Squares Mean (Standard Error) [Percentage of HbA1c]
    -1.87
    (0.094)
    -1.89
    (0.096)
    -2.07
    (0.098)
    0.04
    (0.105)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    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 LS Mean Difference
    Estimated Value -1.91
    Confidence Interval (2-Sided) 95%
    -2.18 to -1.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    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 LS Mean Difference
    Estimated Value -1.93
    Confidence Interval (2-Sided) 95%
    -2.21 to -1.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    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 LS Mean Difference
    Estimated Value -2.11
    Confidence Interval (2-Sided) 95%
    -2.39 to -1.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in Body Weight
    Description Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 121 118 116 112
    Least Squares Mean (Standard Error) [Kilograms (kg)]
    -7.0
    (0.52)
    -7.8
    (0.53)
    -9.5
    (0.54)
    -0.7
    (0.57)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    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 LS Mean Difference
    Estimated Value -6.3
    Confidence Interval (2-Sided) 95%
    -7.8 to -4.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    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 LS Mean Difference
    Estimated Value -7.1
    Confidence Interval (2-Sided) 95%
    -8.6 to -5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    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 LS Mean Difference
    Estimated Value -8.8
    Confidence Interval (2-Sided) 95%
    -10.3 to -7.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With HbA1c Target Value of <7%
    Description Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
    Time Frame Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 121 118 116 112
    Number [Percentage of participants]
    86.78
    71.7%
    91.53
    75.6%
    87.93
    72.7%
    19.64
    17.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    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 49.00
    Confidence Interval (2-Sided) 95%
    21.12 to 113.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    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 80.39
    Confidence Interval (2-Sided) 95%
    31.80 to 203.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    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 52.95
    Confidence Interval (2-Sided) 95%
    22.30 to 125.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in Fasting Serum Glucose
    Description Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 121 118 116 112
    Least Squares Mean (Standard Error) [milligram per Deciliter (mg/dL)]
    -43.6
    (3.40)
    -45.9
    (3.45)
    -49.3
    (3.62)
    12.9
    (4.00)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.776
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -11.9 to 8.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.622
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -13.0 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.908
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.6
    Confidence Interval (2-Sided) 95%
    -11.1 to 9.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants With HbA1c Target Value of <5.7%
    Description Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
    Time Frame Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 121 118 116 112
    Number [Percentage of participants]
    33.88
    28%
    30.51
    25.2%
    51.72
    42.7%
    0.89
    0.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    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 40.28
    Confidence Interval (2-Sided) 95%
    7.74 to 209.71
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    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 34.12
    Confidence Interval (2-Sided) 95%
    6.53 to 178.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    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 85.13
    Confidence Interval (2-Sided) 95%
    16.36 to 443.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
    Description The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares).
    Time Frame Baseline, Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 115 111 108 101
    Morning Premeal - Fasting
    -46.9
    (2.09)
    -47.9
    (2.11)
    -45.7
    (2.23)
    -9.2
    (2.53)
    Morning 2-hour Postmeal
    -69.5
    (3.41)
    -61.4
    (3.44)
    -68.9
    (3.66)
    -11.6
    (4.12)
    Midday Premeal
    -43.5
    (2.80)
    -42.5
    (2.82)
    -42.7
    (3.00)
    -2.6
    (3.42)
    Midday 2-hour Postmeal
    -64.2
    (3.60)
    -60.0
    (3.63)
    -63.4
    (3.84)
    -12.7
    (4.33)
    Evening Premeal
    -44.8
    (2.80)
    -45.1
    (2.82)
    -42.3
    (3.02)
    -5.8
    (3.38)
    Evening 2-hour Postmeal
    -61.9
    (3.76)
    -62.8
    (3.81)
    -63.5
    (4.03)
    -10.3
    (4.52)
    Bedtime
    -57.0
    (3.49)
    -59.8
    (3.52)
    -60.8
    (3.66)
    -9.1
    (4.10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments Morning Premeal - Fasting
    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 LS Mean Difference
    Estimated Value -37.7
    Confidence Interval (2-Sided) 95%
    -44.1 to -31.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments Morning Premeal - Fasting
    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 LS Mean Difference
    Estimated Value -38.6
    Confidence Interval (2-Sided) 95%
    -45.1 to -32.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    Comments Morning Premeal - Fasting
    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 LS Mean Difference
    Estimated Value -36.5
    Confidence Interval (2-Sided) 95%
    -43.1 to -29.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments Morning 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -57.9
    Confidence Interval (2-Sided) 95%
    -68.4 to -47.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments Morning 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -49.7
    Confidence Interval (2-Sided) 95%
    -60.3 to -39.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    Comments Morning 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -57.3
    Confidence Interval (2-Sided) 95%
    -68.1 to -46.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments Midday Premeal
    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 LS Mean Difference
    Estimated Value -40.9
    Confidence Interval (2-Sided) 95%
    -49.6 to -32.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments Midday Premeal
    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 LS Mean Difference
    Estimated Value -39.9
    Confidence Interval (2-Sided) 95%
    -48.6 to -31.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    Comments Midday Premeal
    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 LS Mean Difference
    Estimated Value -40.0
    Confidence Interval (2-Sided) 95%
    -49.0 to -31.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments Midday 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -51.4
    Confidence Interval (2-Sided) 95%
    -62.5 to -40.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments Midday 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -47.3
    Confidence Interval (2-Sided) 95%
    -58.4 to -36.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    Comments Midday 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -50.7
    Confidence Interval (2-Sided) 95%
    -62.1 to -39.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments Evening Premeal
    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 LS Mean Difference
    Estimated Value -39.0
    Confidence Interval (2-Sided) 95%
    -47.6 to -30.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments Evening Premeal
    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 LS Mean Difference
    Estimated Value -39.2
    Confidence Interval (2-Sided) 95%
    -47.9 to -30.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    Comments Evening Premeal
    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 LS Mean Difference
    Estimated Value -36.4
    Confidence Interval (2-Sided) 95%
    -45.3 to -27.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments Evening 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -51.7
    Confidence Interval (2-Sided) 95%
    -63.2 to -40.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments Evening 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -52.5
    Confidence Interval (2-Sided) 95%
    -64.1 to -40.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    Comments Evening 2-hour Postmeal
    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 LS Mean Difference
    Estimated Value -53.2
    Confidence Interval (2-Sided) 95%
    -65.1 to -41.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    Comments Bedtime
    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 LS Mean Difference
    Estimated Value -48.0
    Confidence Interval (2-Sided) 95%
    -58.6 to -37.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    Comments Bedtime
    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 LS Mean Difference
    Estimated Value -50.7
    Confidence Interval (2-Sided) 95%
    -61.3 to -40.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    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 LS Mean Difference
    Estimated Value -51.7
    Confidence Interval (2-Sided) 95%
    -62.6 to -40.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants Who Achieved Weight Loss ≥5%
    Description Percentage of Participants who Achieved Weight Loss ≥5%.
    Time Frame Week 40

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 121 118 116 112
    Number [Percentage of participants]
    66.94
    55.3%
    77.97
    64.4%
    76.72
    63.4%
    14.29
    12.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 5 mg Tirzepatide, Placebo
    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 12.40
    Confidence Interval (2-Sided) 95%
    6.43 to 23.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection 10 mg Tirzepatide, Placebo
    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 21.13
    Confidence Interval (2-Sided) 95%
    10.59 to 42.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection 15 mg Tirzepatide, Placebo
    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 20.10
    Confidence Interval (2-Sided) 95%
    10.09 to 40.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
    Description The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL) (<3.0 mmol/L] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Prior Use of OAM (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable.
    Time Frame Baseline through end of safety follow-up (up to week 44)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week. Participants received placebo as subcutaneous injection once a week.
    Measure Participants 121 119 120 115
    Mean (Standard Error) [Episodes/participant/365.25 days]
    0.02
    (0.002)
    0.02
    (0.002)
    0.02
    (0.002)
    0.04
    (0.028)
    9. Secondary Outcome
    Title Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide
    Description Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported.
    Time Frame Week 7, 15 and 23

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug and had evaluable PK data.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Arm/Group Description Participants received 5 mg of tirzepatide as subcutaneous injection once a week. Participants received 10mg of tirzepatide as subcutaneous injection once a week. Participants received 15mg of tirzepatide as subcutaneous injection once a week.
    Measure Participants 121 118 120
    Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours per milliliter (h*ng/mL)]
    86900
    (25.4)
    171000
    (26.2)
    252000
    (23.3)

    Adverse Events

    Time Frame Baseline to end of Safety follow-up (up to 44 weeks)
    Adverse Event Reporting Description All randomized participants who received at least one dose of study drug.
    Arm/Group Title 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Arm/Group Description Participants received 5 mg of Tirzepatide as subcutaneous injection, once weekly. Participants received 10 mg of Tirzepatide as subcutaneous injection, once weekly. Participants received 15 mg of Tirzepatide as subcutaneous injection, once weekly. Participants received placebo as subcutaneous injection, once weekly.
    All Cause Mortality
    5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/121 (0%) 0/121 (0%) 0/121 (0%) 1/115 (0.9%)
    Serious Adverse Events
    5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/121 (4.1%) 2/121 (1.7%) 1/121 (0.8%) 3/115 (2.6%)
    Cardiac disorders
    Acute myocardial infarction 0/121 (0%) 0 0/121 (0%) 0 0/121 (0%) 0 1/115 (0.9%) 1
    Cardiac failure 0/121 (0%) 0 0/121 (0%) 0 0/121 (0%) 0 1/115 (0.9%) 1
    Supraventricular tachycardia 1/121 (0.8%) 1 0/121 (0%) 0 0/121 (0%) 0 0/115 (0%) 0
    Gastrointestinal disorders
    Colitis ischaemic 1/121 (0.8%) 1 0/121 (0%) 0 0/121 (0%) 0 0/115 (0%) 0
    Infections and infestations
    Clostridium difficile infection 0/121 (0%) 0 1/121 (0.8%) 1 0/121 (0%) 0 0/115 (0%) 0
    Pneumonia 0/121 (0%) 0 1/121 (0.8%) 1 0/121 (0%) 0 0/115 (0%) 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain 0/121 (0%) 0 0/121 (0%) 0 1/121 (0.8%) 1 0/115 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 1/121 (0.8%) 1 0/121 (0%) 0 0/121 (0%) 0 0/115 (0%) 0
    Cholangiocarcinoma 0/121 (0%) 0 0/121 (0%) 0 0/121 (0%) 0 1/115 (0.9%) 1
    Nervous system disorders
    Syncope 1/121 (0.8%) 1 0/121 (0%) 0 0/121 (0%) 0 0/115 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis 1/121 (0.8%) 1 0/121 (0%) 0 0/121 (0%) 0 0/115 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure 1/121 (0.8%) 1 0/121 (0%) 0 0/121 (0%) 0 0/115 (0%) 0
    Vascular disorders
    Peripheral arterial occlusive disease 1/121 (0.8%) 1 0/121 (0%) 0 0/121 (0%) 0 0/115 (0%) 0
    Other (Not Including Serious) Adverse Events
    5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 50/121 (41.3%) 55/121 (45.5%) 53/121 (43.8%) 54/115 (47%)
    Gastrointestinal disorders
    Constipation 7/121 (5.8%) 11 6/121 (5%) 6 8/121 (6.6%) 9 1/115 (0.9%) 1
    Diarrhoea 14/121 (11.6%) 21 17/121 (14%) 19 14/121 (11.6%) 20 9/115 (7.8%) 15
    Dyspepsia 11/121 (9.1%) 15 8/121 (6.6%) 12 7/121 (5.8%) 7 4/115 (3.5%) 4
    Nausea 14/121 (11.6%) 31 16/121 (13.2%) 82 22/121 (18.2%) 50 7/115 (6.1%) 8
    Vomiting 4/121 (3.3%) 6 3/121 (2.5%) 3 7/121 (5.8%) 9 2/115 (1.7%) 3
    Infections and infestations
    Influenza 7/121 (5.8%) 7 3/121 (2.5%) 3 0/121 (0%) 0 2/115 (1.7%) 2
    Nasopharyngitis 7/121 (5.8%) 7 8/121 (6.6%) 13 8/121 (6.6%) 8 10/115 (8.7%) 11
    Metabolism and nutrition disorders
    Decreased appetite 5/121 (4.1%) 5 8/121 (6.6%) 9 10/121 (8.3%) 10 1/115 (0.9%) 1
    Hyperglycaemia 4/121 (3.3%) 4 5/121 (4.1%) 7 3/121 (2.5%) 3 31/115 (27%) 31
    Nervous system disorders
    Headache 5/121 (4.1%) 9 4/121 (3.3%) 7 5/121 (4.1%) 8 9/115 (7.8%) 12

    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:
    NCT03954834
    Other Study ID Numbers:
    • 17000
    • I8F-MC-GPGK
    First Posted:
    May 17, 2019
    Last Update Posted:
    Oct 20, 2021
    Last Verified:
    Oct 1, 2021