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
Enrollment
53
Locations
4
Arms
16.9
Actual Duration (Months)
9
Patients Per Site
0.5
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1National Research InstituteHuntington ParkCaliforniaUnited States90255
    2National Research InstituteLos AngelesCaliforniaUnited States90057
    3Catalina Research Institute, LLCMontclairCaliforniaUnited States91763
    4Valley Clinical Trials, Inc.NorthridgeCaliforniaUnited States91325
    5National Research InstitutePanorama CityCaliforniaUnited States91402
    6Southern California DermatologySanta AnaCaliforniaUnited States92701
    7Clinical Research of South FloridaCoral GablesFloridaUnited States33134
    8Encore Medical Research, LLCHollywoodFloridaUnited States33021
    9Axcess Medical ResearchLoxahatchee GrovesFloridaUnited States33470
    10South Florida Wellness & Clinical Research InstituteMargateFloridaUnited States33063
    11Suncoast Research Group, LLCMiamiFloridaUnited States33135
    12Agile Clinical Research TrialsAtlantaGeorgiaUnited States30328
    13Sky Clinical Research NetworkAtlantaGeorgiaUnited States30331
    14Cotton O'Neil ClinicTopekaKansasUnited States66606
    15Clinical Research ProfessionalsChesterfieldMissouriUnited States63005
    16StudyMetrix Research, LLCSaint PetersMissouriUnited States63303
    17Aventiv ResearchColumbusOhioUnited States43213
    18Intend ResearchNormanOklahomaUnited States73069
    19The Corvallis Clinic P.C.CorvallisOregonUnited States97330
    20Heritage Valley Medical Group, Inc.BeaverPennsylvaniaUnited States15009
    21Family Medical AssociatesLevittownPennsylvaniaUnited States19056
    22Preferred Primary Care PhysiciansPittsburghPennsylvaniaUnited States15236
    23Preferred Primary Care PhysiciansUniontownPennsylvaniaUnited States15401
    24Dallas Diabetes Endocrine CenterDallasTexasUnited States75230
    25Clinical Trials of Texas, Inc.San AntonioTexasUnited States78229
    26Consano Clinical ResearchShavano ParkTexasUnited States78231
    27Capital Clinical Research CenterOlympiaWashingtonUnited States98502
    28Rockwood Clinic Research CenterSpokaneWashingtonUnited States99220
    29Dr. Jivraj Mehta Smarak Health FoundationAhmedabadGujaratIndia380007
    30Bangalore Medical College and Research InstituteBangaloreKarnatakaIndia560 002
    31M S Ramaiah Medical College HospitalBangaloreKarnatakaIndia560054
    32BSES Municipal General HsptlMumbaiMaharashtraIndia400058
    33Ruby Hall Clinic and Grant Medical FoundationPuneMaharashtraIndia411001
    34Vijay Vallabh HospitalVirarMaharashtraIndia401303
    35Lifepoint Multispecialty HsptlWakadPuneIndia411057
    36Ramdevrao HospitalHyderabadTelanganaIndia500072
    37Gandhi HospitalTelanganaIndia500003
    38Minamiakatsuka ClinicMitoIbarakiJapan311-4153
    39Takai Naika ClinicKamakuraKanagawaJapan247-0056
    40Tsuruma Kaneshiro Diabetes ClinicYamatoKanagawaJapan242-0004
    41Yokohama Minoru ClinicYokohamaKanagawaJapan232-0064
    42Takatsuki Red Cross HospitalTakatsukiOsakaJapan569-1096
    43Meiwa HospitalChiyodakuTokyoJapan101 0041
    44Tokyo-Eki Center-building ClinicChuo-kuTokyoJapan103-0027
    45Tokyo Center ClinicChuo-kuTokyoJapan103-0028
    46IHL Shinagawa East One Medical ClinicMinato-kuTokyoJapan108 0075
    47Sato Naika ClinicOta-kuTokyoJapan143-0015
    48Hospital Universitario UANLMonterreyNuevo LeónMexico64460
    49Unidad Medica para la Salud Integral (UMSI)MonterreyNuevo LeónMexico66465
    50Centro de Estudios de Investigacion Metabolicos y CardiovascMaderoTamaulipasMexico89440
    51Investigacion en Salud y Metabolismo S.CChihuahuaMexico31217
    52Clinical Research Puerto Rico, Inc.San JuanPuerto Rico00909
    53GCM Medical Group PSCSan JuanPuerto Rico00917

    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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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
    STARTED121121121115
    Received at Least One Dose of Study Drug121121121115
    COMPLETED11411210399
    NOT COMPLETED791816

    Baseline Characteristics

    Arm/Group Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlaceboTotal
    Arm/Group DescriptionParticipants 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 Participants121121121115478
    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
    TitleChange From Baseline in Hemoglobin A1c (HbA1c)
    DescriptionHbA1c 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 FrameBaseline, 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants121118116112
    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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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
    TitleChange From Baseline in Body Weight
    DescriptionLeast 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 FrameBaseline, 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants121118116112
    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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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
    TitlePercentage of Participants With HbA1c Target Value of <7%
    DescriptionHemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
    Time FrameWeek 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants121118116112
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value49.00
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value80.39
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value52.95
    Confidence Interval (2-Sided) 95%
    22.30 to 125.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    TitleChange From Baseline in Fasting Serum Glucose
    DescriptionFasting 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 FrameBaseline, 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants121118116112
    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 Hypothesisp-Value0.776
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value0.622
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value0.908
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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
    TitlePercentage of Participants With HbA1c Target Value of <5.7%
    DescriptionHemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
    Time FrameWeek 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants121118116112
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value40.28
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value34.12
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value85.13
    Confidence Interval (2-Sided) 95%
    16.36 to 443.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    TitleMean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
    DescriptionThe 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 FrameBaseline, 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants115111108101
    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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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 Hypothesisp-Value<0.001
    Comments
    MethodMixed Models Analysis
    Comments
    Method of EstimationEstimation ParameterLS 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
    TitlePercentage of Participants Who Achieved Weight Loss ≥5%
    DescriptionPercentage of Participants who Achieved Weight Loss ≥5%.
    Time FrameWeek 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants121118116112
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value12.40
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value21.13
    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 Hypothesisp-Value<0.001
    Comments
    MethodRegression, Logistic
    Comments
    Method of EstimationEstimation ParameterOdds Ratio (OR)
    Estimated Value20.10
    Confidence Interval (2-Sided) 95%
    10.09 to 40.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    TitleRate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
    DescriptionThe 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 FrameBaseline 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Participants121119120115
    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
    TitlePharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide
    DescriptionPharmacokinetics (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 FrameWeek 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
    Arm/Group DescriptionParticipants 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 Participants121118120
    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 FrameBaseline 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 Title5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Arm/Group DescriptionParticipants 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 Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/121 (0%) 0/121 (0%) 0/121 (0%) 1/115 (0.9%)
    Serious Adverse Events
    5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/121 (4.1%) 2/121 (1.7%) 1/121 (0.8%) 3/115 (2.6%)
    Cardiac disorders
    Acute myocardial infarction0/121 (0%) 00/121 (0%) 00/121 (0%) 01/115 (0.9%) 1
    Cardiac failure0/121 (0%) 00/121 (0%) 00/121 (0%) 01/115 (0.9%) 1
    Supraventricular tachycardia1/121 (0.8%) 10/121 (0%) 00/121 (0%) 00/115 (0%) 0
    Gastrointestinal disorders
    Colitis ischaemic1/121 (0.8%) 10/121 (0%) 00/121 (0%) 00/115 (0%) 0
    Infections and infestations
    Clostridium difficile infection0/121 (0%) 01/121 (0.8%) 10/121 (0%) 00/115 (0%) 0
    Pneumonia0/121 (0%) 01/121 (0.8%) 10/121 (0%) 00/115 (0%) 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain0/121 (0%) 00/121 (0%) 01/121 (0.8%) 10/115 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma1/121 (0.8%) 10/121 (0%) 00/121 (0%) 00/115 (0%) 0
    Cholangiocarcinoma0/121 (0%) 00/121 (0%) 00/121 (0%) 01/115 (0.9%) 1
    Nervous system disorders
    Syncope1/121 (0.8%) 10/121 (0%) 00/121 (0%) 00/115 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis1/121 (0.8%) 10/121 (0%) 00/121 (0%) 00/115 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure1/121 (0.8%) 10/121 (0%) 00/121 (0%) 00/115 (0%) 0
    Vascular disorders
    Peripheral arterial occlusive disease1/121 (0.8%) 10/121 (0%) 00/121 (0%) 00/115 (0%) 0
    Other (Not Including Serious) Adverse Events
    5 mg Tirzepatide10 mg Tirzepatide15 mg TirzepatidePlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total50/121 (41.3%) 55/121 (45.5%) 53/121 (43.8%) 54/115 (47%)
    Gastrointestinal disorders
    Constipation7/121 (5.8%) 116/121 (5%) 68/121 (6.6%) 91/115 (0.9%) 1
    Diarrhoea14/121 (11.6%) 2117/121 (14%) 1914/121 (11.6%) 209/115 (7.8%) 15
    Dyspepsia11/121 (9.1%) 158/121 (6.6%) 127/121 (5.8%) 74/115 (3.5%) 4
    Nausea14/121 (11.6%) 3116/121 (13.2%) 8222/121 (18.2%) 507/115 (6.1%) 8
    Vomiting4/121 (3.3%) 63/121 (2.5%) 37/121 (5.8%) 92/115 (1.7%) 3
    Infections and infestations
    Influenza7/121 (5.8%) 73/121 (2.5%) 30/121 (0%) 02/115 (1.7%) 2
    Nasopharyngitis7/121 (5.8%) 78/121 (6.6%) 138/121 (6.6%) 810/115 (8.7%) 11
    Metabolism and nutrition disorders
    Decreased appetite5/121 (4.1%) 58/121 (6.6%) 910/121 (8.3%) 101/115 (0.9%) 1
    Hyperglycaemia4/121 (3.3%) 45/121 (4.1%) 73/121 (2.5%) 331/115 (27%) 31
    Nervous system disorders
    Headache5/121 (4.1%) 94/121 (3.3%) 75/121 (4.1%) 89/115 (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/TitleChief Medical Officer
    OrganizationEli Lilly and Company
    Phone800-545-5979
    EmailClinicalTrials.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