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    Clinical Trial Results:
    A Phase 2 Study of Once-Weekly LY3298176 Compared with Placebo and Dulaglutide in Patients with Type 2 Diabetes Mellitus

    Summary
    EudraCT number
    		 2016-004179-33
    Trial protocol
    		 SK   PL  
    Global end of trial date
    01 Aug 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Aug 2019
    First version publication date
    30 Aug 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    I8F-MC-GPGB
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03131687
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16335
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Aug 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Aug 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate the efficacy of the study drug tirzepatide in participants with type 2 diabetes mellitus.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 May 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 1 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Puerto Rico: 16
    Country: Number of subjects enrolled
    United States: 234
    Country: Number of subjects enrolled
    Poland: 31
    Country: Number of subjects enrolled
    Slovakia: 35
    Worldwide total number of subjects
    316
    EEA total number of subjects
    66
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    258
    From 65 to 84 years
    58
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 No Text Available

    Pre-assignment
    Screening details
    		 Two additional patients were randomized in the US but chose not to take study drug and are not included in the number of patients enrolled. Thus, 318 patients were randomized but 316 took study drug and all data presented are for patients who took at least 1 dose of study drug (316 patients).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Tirzepatide Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tirzepatide placebo administered subcutaneously (SC) once weekly.

    Investigational medicinal product name
    Dulaglutide Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dulaglutide placebo administered subcutaneously (SC) once weekly.

    Arm title
    		 1 mg Tirzepatide
    Arm description
    		 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    tirzepatide
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 mg tirzepatide administered SC once weekly

    Investigational medicinal product name
    Dulaglutide Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dulaglutide placebo administered SC once weekly.

    Arm title
    		 5 mg Tirzepatide
    Arm description
    		 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    tirzepatide
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    5 mg tirzepatide administered SC once weekly

    Investigational medicinal product name
    Dulaglutide placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dulaglutide placebo administered SC once weekly.

    Arm title
    		 10 mg Tirzepatide
    Arm description
    		 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    tirzepatide
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    10 mg tirzepatide administered SC once weekly.

    Investigational medicinal product name
    Dulaglutide Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dulaglutide placebo administered SC once weekly.

    Arm title
    		 15 mg Tirzepatide
    Arm description
    		 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    tirzepatide
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    15 mg tirzepatide administered SC once weekly.

    Investigational medicinal product name
    Dulaglutide Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dulaglutide placebo administered SC once weekly.

    Arm title
    		 1.5 mg Dulaglutide
    Arm description
    		 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Dulaglutide
    Investigational medicinal product code
    Other name
    LY2189265
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1.5 mg Dulaglutide administered SC once weekly.

    Investigational medicinal product name
    Tirzepatide Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tirzepatide placebo administered SC once weekly

    Number of subjects in period 1
    		Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Started
    51
    52
    55
    51
    53
    54
    Received at least one dose of study drug
    51
    52
    55
    51
    53
    54
    Completed
    45
    44
    52
    48
    45
    49
    Not completed
    6
    8
    3
    3
    8
    5
         Consent withdrawn by subject
    3
    3
    3
    1
    2
    1
         Adverse event, non-fatal
    -
    1
    -
    1
    2
    2
         Death
    1
    -
    -
    -
    -
    -
         Lost to follow-up
    1
    4
    -
    1
    4
    2
         Participant Started New Diabetic Drug
    1
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.

    Reporting group title
    1 mg Tirzepatide
    Reporting group description
    		 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    5 mg Tirzepatide
    Reporting group description
    		 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    10 mg Tirzepatide
    Reporting group description
    		 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    15 mg Tirzepatide
    Reporting group description
    		 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    1.5 mg Dulaglutide
    Reporting group description
    		 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.

    Reporting group values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide Total
    Number of subjects
    		 51 52 55 51 53 54 316
    Age categorical
    Units: Subjects
    Age continuous
    All randomized participants who received at least one dose of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 56.6 ( 8.85 ) 57.4 ( 8.85 ) 57.9 ( 8.22 ) 56.5 ( 9.92 ) 56.0 ( 7.58 ) 58.7 ( 7.81 ) -
    Gender categorical
    All randomized participants who received at least one dose of study drug.
    Units: Subjects
        Female
    		 22 23 21 21 31 30 148
        Male
    		 29 29 34 30 22 24 168
    Ethnicity (NIH/OMB)
    All randomized participants who received at least one dose of study drug.
    Units: Subjects
        Hispanic or Latino
    		 27 25 22 26 23 19 142
        Not Hispanic or Latino
    		 19 23 23 20 27 27 139
        Unknown or Not Reported
    		 5 4 10 5 3 8 35
    Race (NIH/OMB)
    All randomized participants who received at least one dose of study drug.
    Units: Subjects
        American Indian or Alaska Native
    		 5 4 1 2 2 1 15
        Asian
    		 1 0 0 1 1 2 5
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 1 1 0 2
        Black or African American
    		 2 5 6 7 6 4 30
        White
    		 41 42 46 37 43 44 253
        More than one race
    		 2 1 2 2 0 2 9
        Unknown or Not Reported
    		 0 0 0 1 0 1 2
    Region of Enrollment
    All randomized participants who received at least one dose of study drug.
    Units: Subjects
        Puerto Rico
    		 4 4 3 3 1 1 16
        United States
    		 36 37 38 37 43 43 234
        Poland
    		 6 7 4 6 6 2 31
        Slovakia
    		 5 4 10 5 3 8 35
    Hemoglobin A1C (HbA1c) at Baseline
    Measure Description: HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.
    Units: Percentage of HbA1c
        arithmetic mean (standard deviation)
    		 8.04 ( 0.861 ) 8.21 ( 0.905 ) 8.17 ( 0.961 ) 8.15 ( 1.072 ) 8.13 ( 1.061 ) 8.13 ( 1.954 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.

    Reporting group title
    1 mg Tirzepatide
    Reporting group description
    		 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    5 mg Tirzepatide
    Reporting group description
    		 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    10 mg Tirzepatide
    Reporting group description
    		 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    15 mg Tirzepatide
    Reporting group description
    		 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    1.5 mg Dulaglutide
    Reporting group description
    		 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.

    Primary: Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response

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    End point title
    		 Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
    End point description
    HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. Analysis Population Description (APD): All randomized participants who received at least one dose of study drug and had a baseline and postbaseline excluding data after rescue drug initiation. The Least Squares Mean is Posterior mean.
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    44
    45
    52
    47
    44
    49
    Units: Percentage of HbA1c
        least squares mean (standard deviation)
    -0.06 ( 0.14 )
    -1.06 ( 0.11 )
    -1.73 ( 0.08 )
    -1.89 ( 0.08 )
    -1.94 ( 0.09 )
    -1.21 ( 0.14 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -1.22
         upper limit
    		 -0.79
    Variability estimate
    Standard deviation
    Dispersion value
    0.17
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -1.67
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -1.88
         upper limit
    		 -1.46
    Variability estimate
    Standard deviation
    Dispersion value
    0.17
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -1.83
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -2.04
         upper limit
    		 -1.61
    Variability estimate
    Standard deviation
    Dispersion value
    0.17
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -1.89
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -2.11
         upper limit
    		 -1.67
    Variability estimate
    Standard deviation
    Dispersion value
    0.17

    Secondary: Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response

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    End point title
    		 Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
    End point description
    HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. APD: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value excluding data after rescue drug initiation. The Least Squares Mean is Posterior mean.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    48
    45
    52
    48
    48
    51
    Units: Percentage of HbA1c
        least squares mean (standard deviation)
    -0.05 ( 0.13 )
    -0.94 ( 0.10 )
    -1.54 ( 0.07 )
    -1.68 ( 0.08 )
    -1.72 ( 0.08 )
    -1.08 ( 0.13 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -0.89
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -1.08
         upper limit
    		 -0.71
    Variability estimate
    Standard deviation
    Dispersion value
    0.15
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -1.49
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -1.68
         upper limit
    		 -1.3
    Variability estimate
    Standard deviation
    Dispersion value
    0.15
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -1.62
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -1.82
         upper limit
    		 -1.43
    Variability estimate
    Standard deviation
    Dispersion value
    0.15
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide Bayesian Dose Response
    Statistical analysis description
    Statistics are estimated from a Bayesian hierarchical logistic dose response model along with a titrated integrated two-component prediction model to estimate missing values. The confidence interval is 80% credible set for difference.
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Posterior Mean Difference
    Point estimate
    -1.67
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -1.86
         upper limit
    		 -1.47
    Variability estimate
    Standard deviation
    Dispersion value
    0.15

    Secondary: Change From Baseline to Week 26 in HbA1c

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    End point title
    		 Change From Baseline to Week 26 in HbA1c
    End point description
    HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time. APD: All randomized participants who received at least one dose of study drug who had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    41
    44
    47
    43
    35
    47
    Units: Percentage of HbA1c
        least squares mean (standard error)
    0.1 ( 0.16 )
    -0.7 ( 0.16 )
    -1.6 ( 0.15 )
    -2.0 ( 0.16 )
    -2.4 ( 0.17 )
    -1.1 ( 0.15 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 -0.4
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 -1.3
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.5
         upper limit
    		 -1.6
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    76
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 -2

    Secondary: Change From Baseline to Week 12 in HbA1c

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    End point title
    		 Change From Baseline to Week 12 in HbA1c
    End point description
    HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: Baseline + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time. APD: All randomized participants who received at least one dose of study drug who had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    44
    44
    49
    47
    36
    49
    Units: Percentage of HbA1c
        least squares mean (standard error)
    -0.1 ( 0.13 )
    -0.9 ( 0.13 )
    -1.7 ( 0.13 )
    -2.0 ( 0.13 )
    -2.1 ( 0.15 )
    -1.2 ( 0.13 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 -0.4
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 -1.3
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 -1.5
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 -1.7

    Secondary: Change From Baseline in Body Weight

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    End point title
    		 Change From Baseline in Body Weight
    End point description
    Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with independent variables: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time. APD: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    41
    44
    48
    44
    35
    47
    Units: kilograms (kg)
        least squares mean (standard error)
    -0.4 ( 0.81 )
    -0.9 ( 0.80 )
    -4.8 ( 0.77 )
    -8.7 ( 0.80 )
    -11.3 ( 0.88 )
    -2.7 ( 0.78 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.655
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 1.7
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.6
         upper limit
    		 -2.3
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -8.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.5
         upper limit
    		 -6
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide MMRM
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    76
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -10.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.3
         upper limit
    		 -8.6

    Secondary: Percentage of Participants With 5% or Greater Body Weight Loss From Baseline

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    End point title
    		 Percentage of Participants With 5% or Greater Body Weight Loss From Baseline
    End point description
    Percentage of participants with 5% or greater body weight loss from baseline last observation carried forward (LOCF) analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors. APD: All randomized participants who received at least one dose of study drug excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    51
    52
    55
    51
    53
    54
    Units: percentage of participants
        number (not applicable)
    0
    13.5
    47.3
    70.6
    62.3
    22.2
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.053
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.002
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval

    Secondary: Percentage of Participants With 10% or Greater Body Weight Loss From Baseline

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    End point title
    		 Percentage of Participants With 10% or Greater Body Weight Loss From Baseline
    End point description
    Percentage of participants with 10% or greater body weight loss from baseline LOCF analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors. APD: All randomized participants who received at least one dose of study drug excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    51
    52
    55
    51
    53
    54
    Units: percentage of participants
        number (not applicable)
    0
    5.8
    16.4
    39.2
    37.7
    9.3
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.193
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.036
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.003
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.003
    Method
    		 Regression, Logistic
    Confidence interval

    Secondary: Percentage of Participants Reaching the HbA1c Target of ≤6.5%

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    End point title
    		 Percentage of Participants Reaching the HbA1c Target of ≤6.5%
    End point description
    Percentage of participants with HbA1c ≤6.5% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors. APD: All randomized participants who received at least one dose of study drug excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    51
    52
    55
    50
    53
    54
    Units: percentage of participants
        number (not applicable)
    2.0
    15.4
    63.6
    82.0
    58.5
    38.9
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.03
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval

    Secondary: Percentage of Participants Reaching the HbA1c Target of <7.0%

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    End point title
    		 Percentage of Participants Reaching the HbA1c Target of <7.0%
    End point description
    Percentage of participants with HbA1c <7.0% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors. APD: All randomized participants who received at least one dose of study drug excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    51
    52
    55
    50
    53
    54
    Units: percentage of participants
        number (not applicable)
    11.8
    32.7
    69.1
    90.0
    77.4
    51.9
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.008
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Confidence interval

    Secondary: Change From Baseline in Fasting Blood Glucose

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    End point title
    		 Change From Baseline in Fasting Blood Glucose
    End point description
    Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment*Time. APD: All randomized participants who received at least one dose of study drug who had a baseline and postbaseline value excluding data after study drug discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    40
    44
    48
    44
    35
    46
    Units: milligrams per deciliter (mg/dL)
        least squares mean (standard error)
    15.5 ( 6.66 )
    -6.8 ( 6.43 )
    -40.7 ( 6.23 )
    -60.7 ( 6.36 )
    -57.5 ( 7.10 )
    -21.2 ( 6.40 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.01
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -22.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.4
         upper limit
    		 -5.3
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -56.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -72.9
         upper limit
    		 -39.5
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -76.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -93.3
         upper limit
    		 -59.2
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    15 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -90.9
         upper limit
    		 -55.2

    Secondary: Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)

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    End point title
    		 Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
    End point description
    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, time, treatment*time. APD: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    45
    46
    53
    48
    46
    51
    Units: Millimoles Per Litre (mmol/L)
        least squares mean (standard error)
    0.0 ( 0.03 )
    -0.0 ( 0.03 )
    0.0 ( 0.03 )
    0.0 ( 0.03 )
    0.1 ( 0.03 )
    0.0 ( 0.03 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.396
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.903
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.1
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.536
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.1
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.325
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.1

    Secondary: Change From Baseline in Total Cholesterol

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    End point title
    		 Change From Baseline in Total Cholesterol
    End point description
    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time. APD: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    45
    46
    53
    48
    46
    51
    Units: Millimoles Per Litre (mmol/L)
        least squares mean (standard error)
    0.3 ( 0.13 )
    0.2 ( 0.13 )
    -0.1 ( 0.12 )
    -0.3 ( 0.12 )
    -0.3 ( 0.13 )
    -0.2 ( 0.12 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.565
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.2
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    5 mg Tirzepatide v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.01
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 -0.1
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 -0.2
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 -0.3

    Secondary: Change From Baseline in Triglycerides

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    End point title
    		 Change From Baseline in Triglycerides
    End point description
    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time. APD: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    45
    46
    53
    48
    46
    51
    Units: Millimoles Per Litre (mmol/L)
        least squares mean (standard error)
    0.3 ( 0.16 )
    -0.0 ( 0.16 )
    -0.5 ( 0.15 )
    -0.7 ( 0.15 )
    -0.8 ( 0.16 )
    -0.3 ( 0.15 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.164
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.1
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 -0.4
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 -0.6
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 -0.7

    Secondary: Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)

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    End point title
    		 Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)
    End point description
    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time. APD: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    42
    45
    52
    48
    45
    50
    Units: Millimoles Per Litre (mmol/L)
        least squares mean (standard error)
    0.2 ( 0.12 )
    0.2 ( 0.11 )
    0.0 ( 0.11 )
    -0.0 ( 0.11 )
    -0.1 ( 0.12 )
    -0.1 ( 0.11 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.919
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.3
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.194
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.1
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.145
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.1
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.067
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0

    Secondary: Change From Baseline in Waist Circumference

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    End point title
    		 Change From Baseline in Waist Circumference
    End point description
    LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment*Time. APD: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline value excluding data after treatment discontinuation or rescue drug initiation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    42
    44
    47
    44
    35
    47
    Units: centimeters (cm)
        least squares mean (standard error)
    -1.3 ( 0.91 )
    -2.1 ( 0.89 )
    -5.1 ( 0.86 )
    -7.4 ( 0.88 )
    -10.2 ( 1.00 )
    -2.5 ( 0.87 )
    Statistical analysis title
    		 Placebo, 1 mg Tirzepatide
    Comparison groups
    Placebo v 1 mg Tirzepatide
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.539
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 1.6
    Statistical analysis title
    		 Placebo, 5 mg Tirzepatide
    Comparison groups
    Placebo v 5 mg Tirzepatide
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 -1.5
    Statistical analysis title
    		 Placebo, 10 mg Tirzepatide
    Comparison groups
    Placebo v 10 mg Tirzepatide
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.4
         upper limit
    		 -3.7
    Statistical analysis title
    		 Placebo, 15 mg Tirzepatide
    Comparison groups
    Placebo v 15 mg Tirzepatide
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -8.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.3
         upper limit
    		 -6.4

    Secondary: Number of Participants With Anti-Drug Antibodies

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    End point title
    		 Number of Participants With Anti-Drug Antibodies
    End point description
    Number of Participants With Anti-Drug Antibodies. APD: All randomized participants who received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 30
    End point values
    		 Placebo 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide 1.5 mg Dulaglutide
    Number of subjects analysed
    51
    52
    55
    51
    53
    54
    Units: Participants
    0
    16
    19
    24
    26
    0
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide

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    End point title
    		 Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide [1]
    End point description
    Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide. APD: All randomized participants who received at least one dose of Tirzepatide study drug excluding post rescue data.
    End point type
    Secondary
    End point timeframe
    Predose: Week 1,8,12 and 26; Postdose: Week 1,2,4 and 12
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, PK data were only collected for Tirzepatide and Dulaglutide.
    End point values
    		 1 mg Tirzepatide 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide
    Number of subjects analysed
    52
    55
    51
    53
    Units: Nanograms Per Millilitre (ng/mL)
        geometric mean (geometric coefficient of variation)
    78.6 ( 29 )
    394 ( 29 )
    787 ( 29 )
    1180 ( 29 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up To 34 Weeks
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    LY 1mg
    Reporting group description
    		 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    LY 5mg
    Reporting group description
    		 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    LY 10mg
    Reporting group description
    		 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    LY 15mg
    Reporting group description
    		 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.

    Reporting group title
    Placebo
    Reporting group description
    		 Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.

    Reporting group title
    Dula 1.5mg
    Reporting group description
    		 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.

    Serious adverse events
    		 LY 1mg LY 5mg LY 10mg LY 15mg Placebo Dula 1.5mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 52 (3.85%)
    1 / 55 (1.82%)
    3 / 51 (5.88%)
    2 / 53 (3.77%)
    2 / 51 (3.92%)
    3 / 54 (5.56%)
         number of deaths (all causes)
    0
    0
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    lung adenocarcinoma stage iv
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    1 / 51 (1.96%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Vascular disorders
    accelerated hypertension
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    1 / 53 (1.89%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    coronary artery disease
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery occlusion
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    torsade de pointes
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ventricular fibrillation
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    cluster headache
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    1 / 53 (1.89%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vertebrobasilar insufficiency
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    1 / 53 (1.89%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    enteritis
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    1 / 53 (1.89%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    mesenteric vein thrombosis
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    1 / 51 (1.96%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancreatitis acute
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 55 (1.82%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholecystitis
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    1 / 51 (1.96%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    1 / 51 (1.96%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    back pain
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    1 / 54 (1.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pathological fracture
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    1 / 51 (1.96%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    perirectal abscess
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    1 / 53 (1.89%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    2 / 51 (3.92%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    lactic acidosis
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 LY 1mg LY 5mg LY 10mg LY 15mg Placebo Dula 1.5mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 52 (32.69%)
    29 / 55 (52.73%)
    32 / 51 (62.75%)
    39 / 53 (73.58%)
    17 / 51 (33.33%)
    31 / 54 (57.41%)
    Investigations
    amylase increased
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    2 / 55 (3.64%)
    4 / 51 (7.84%)
    1 / 53 (1.89%)
    1 / 51 (1.96%)
    0 / 54 (0.00%)
         occurrences all number
    0
    3
    7
    3
    1
    0
    lipase increased
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    3 / 55 (5.45%)
    4 / 51 (7.84%)
    2 / 53 (3.77%)
    1 / 51 (1.96%)
    1 / 54 (1.85%)
         occurrences all number
    1
    3
    7
    3
    1
    1
    weight decreased
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    2 / 52 (3.85%)
    2 / 55 (3.64%)
    5 / 51 (9.80%)
    2 / 53 (3.77%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences all number
    2
    2
    5
    2
    0
    0
    Injury, poisoning and procedural complications
    contusion
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    3 / 55 (5.45%)
    0 / 51 (0.00%)
    0 / 53 (0.00%)
    2 / 51 (3.92%)
    1 / 54 (1.85%)
         occurrences all number
    0
    3
    0
    0
    2
    1
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 55 (0.00%)
    0 / 51 (0.00%)
    1 / 53 (1.89%)
    1 / 51 (1.96%)
    3 / 54 (5.56%)
         occurrences all number
    0
    0
    0
    1
    1
    3
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    4 / 52 (7.69%)
    2 / 55 (3.64%)
    2 / 51 (3.92%)
    5 / 53 (9.43%)
    2 / 51 (3.92%)
    1 / 54 (1.85%)
         occurrences all number
    4
    2
    2
    5
    3
    1
    headache
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    2 / 52 (3.85%)
    2 / 55 (3.64%)
    1 / 51 (1.96%)
    5 / 53 (9.43%)
    2 / 51 (3.92%)
    1 / 54 (1.85%)
         occurrences all number
    2
    2
    1
    5
    2
    1
    Gastrointestinal disorders
    abdominal discomfort
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 55 (1.82%)
    1 / 51 (1.96%)
    4 / 53 (7.55%)
    2 / 51 (3.92%)
    0 / 54 (0.00%)
         occurrences all number
    0
    1
    2
    7
    2
    0
    abdominal distension
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    2 / 55 (3.64%)
    5 / 51 (9.80%)
    4 / 53 (7.55%)
    1 / 51 (1.96%)
    3 / 54 (5.56%)
         occurrences all number
    0
    2
    5
    4
    1
    3
    abdominal pain upper
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 55 (1.82%)
    0 / 51 (0.00%)
    3 / 53 (5.66%)
    1 / 51 (1.96%)
    1 / 54 (1.85%)
         occurrences all number
    0
    1
    0
    3
    1
    1
    constipation
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    2 / 55 (3.64%)
    6 / 51 (11.76%)
    2 / 53 (3.77%)
    0 / 51 (0.00%)
    3 / 54 (5.56%)
         occurrences all number
    1
    2
    6
    2
    0
    3
    diarrhoea
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    7 / 52 (13.46%)
    13 / 55 (23.64%)
    12 / 51 (23.53%)
    17 / 53 (32.08%)
    2 / 51 (3.92%)
    9 / 54 (16.67%)
         occurrences all number
    13
    17
    13
    23
    2
    12
    dyspepsia
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 55 (1.82%)
    6 / 51 (11.76%)
    2 / 53 (3.77%)
    0 / 51 (0.00%)
    2 / 54 (3.70%)
         occurrences all number
    0
    2
    7
    2
    0
    2
    nausea
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    2 / 52 (3.85%)
    11 / 55 (20.00%)
    11 / 51 (21.57%)
    21 / 53 (39.62%)
    3 / 51 (5.88%)
    16 / 54 (29.63%)
         occurrences all number
    2
    17
    13
    29
    3
    22
    vomiting
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    2 / 52 (3.85%)
    4 / 55 (7.27%)
    8 / 51 (15.69%)
    14 / 53 (26.42%)
    1 / 51 (1.96%)
    5 / 54 (9.26%)
         occurrences all number
    2
    8
    9
    20
    1
    6
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 55 (1.82%)
    0 / 51 (0.00%)
    3 / 53 (5.66%)
    1 / 51 (1.96%)
    1 / 54 (1.85%)
         occurrences all number
    1
    1
    0
    3
    1
    1
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 55 (1.82%)
    3 / 51 (5.88%)
    0 / 53 (0.00%)
    3 / 51 (5.88%)
    2 / 54 (3.70%)
         occurrences all number
    1
    1
    3
    0
    4
    2
    influenza
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    2 / 52 (3.85%)
    2 / 55 (3.64%)
    4 / 51 (7.84%)
    1 / 53 (1.89%)
    1 / 51 (1.96%)
    2 / 54 (3.70%)
         occurrences all number
    2
    2
    4
    1
    1
    2
    nasopharyngitis
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    3 / 55 (5.45%)
    2 / 51 (3.92%)
    3 / 53 (5.66%)
    2 / 51 (3.92%)
    6 / 54 (11.11%)
         occurrences all number
    2
    3
    5
    6
    3
    6
    upper respiratory tract infection
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    1 / 52 (1.92%)
    3 / 55 (5.45%)
    2 / 51 (3.92%)
    1 / 53 (1.89%)
    3 / 51 (5.88%)
    4 / 54 (7.41%)
         occurrences all number
    1
    3
    3
    1
    3
    5
    urinary tract infection
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    2 / 52 (3.85%)
    2 / 55 (3.64%)
    1 / 51 (1.96%)
    4 / 53 (7.55%)
    0 / 51 (0.00%)
    0 / 54 (0.00%)
         occurrences all number
    2
    2
    1
    4
    0
    0
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 21.0
         subjects affected / exposed
    2 / 52 (3.85%)
    11 / 55 (20.00%)
    13 / 51 (25.49%)
    10 / 53 (18.87%)
    1 / 51 (1.96%)
    3 / 54 (5.56%)
         occurrences all number
    2
    12
    14
    13
    1
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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