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    Clinical Trial Results:
    A Randomized, Phase 3, Open-label Trial Comparing the Effect of the Addition of Tirzepatide Once Weekly versus Insulin Lispro (U100) Three Times Daily in Participants with Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) with or without Metformin

    Summary
    EudraCT number
    		 2020-000284-23
    Trial protocol
    		 DE   HU   CZ   SK   GR   IT  
    Global end of trial date
    01 Nov 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Oct 2023
    First version publication date
    26 Oct 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I8F-MC-GPHD
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04537923
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 17204
    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 Nov 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Nov 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to insulin lispro (U100) three times a day in participants with type 2 diabetes that are already on insulin glargine (U100), with or without metformin.
    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
    19 Oct 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 417
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Brazil: 281
    Country: Number of subjects enrolled
    Czechia: 57
    Country: Number of subjects enrolled
    Germany: 47
    Country: Number of subjects enrolled
    Greece: 15
    Country: Number of subjects enrolled
    Hungary: 19
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Mexico: 118
    Country: Number of subjects enrolled
    Romania: 78
    Country: Number of subjects enrolled
    Russian Federation: 107
    Country: Number of subjects enrolled
    Slovakia: 83
    Country: Number of subjects enrolled
    Spain: 25
    Country: Number of subjects enrolled
    Turkey: 4
    Country: Number of subjects enrolled
    United States: 169
    Worldwide total number of subjects
    1428
    EEA total number of subjects
    332
    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)
    980
    From 65 to 84 years
    445
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 No Text Available

    Pre-assignment
    Screening details
    		 No Text Available

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 5 mg Tirzepatide
    Arm description
    		 Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tirzepatide 5 mg
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tirzepatide administered SC once a week.

    Arm title
    		 10 mg Tirzepatide
    Arm description
    		 Participants received 10 mg tirzepatide administered SC once a week.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tirzepatide 10 mg
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tirzepatide administered SC once a week.

    Arm title
    		 15 mg Tirzepatide
    Arm description
    		 Participants received 15 mg tirzepatide administered SC once a week.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tirzepatide 15 mg
    Investigational medicinal product code
    Other name
    LY3298176
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tirzepatide administered SC once a week.

    Arm title
    		 Insulin Lispro
    Arm description
    		 Participants received Insulin lispro 100 units per milliliter (U100) administered SC three times a day.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Insulin Lispro
    Investigational medicinal product code
    Other name
    Humalog
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Insulin Lispro 100 units per milliliter (U100) administered SC three times a day.

    Number of subjects in period 1
    		5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Started
    243
    238
    236
    711
    Received at Least One Dose of Study Drug
    243
    238
    225
    708
    Completed
    228
    228
    225
    623
    Not completed
    15
    10
    11
    88
         Missed study visits
    2
    -
    -
    3
         Sponsor's decision
    -
    -
    1
    1
         Consent withdrawn by subject
    4
    4
    4
    58
         Safety reasons
    1
    -
    -
    -
         Physician decision
    1
    -
    2
    5
         Adverse event, non-fatal
    2
    1
    2
    4
         Death
    3
    3
    1
    11
         Pregnancy
    1
    -
    -
    -
         Lost to follow-up
    1
    2
    1
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    5 mg Tirzepatide
    Reporting group description
    		 Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

    Reporting group title
    10 mg Tirzepatide
    Reporting group description
    		 Participants received 10 mg tirzepatide administered SC once a week.

    Reporting group title
    15 mg Tirzepatide
    Reporting group description
    		 Participants received 15 mg tirzepatide administered SC once a week.

    Reporting group title
    Insulin Lispro
    Reporting group description
    		 Participants received Insulin lispro 100 units per milliliter (U100) administered SC three times a day.

    Reporting group values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro Total
    Number of subjects
    		 243 238 236 711 1428
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.0 ± 10.2 59.6 ± 9.4 58.2 ± 9.6 59.00 ± 9.74 -
    Gender categorical
    Units: Subjects
        Female
    		 144 149 133 398 824
        Male
    		 99 89 103 313 604
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 148 142 149 446 885
        Not Hispanic or Latino
    		 95 93 87 261 536
        Unknown or Not Reported
    		 0 3 0 4 7
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 1 2 3
        Asian
    		 2 0 2 4 8
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 11 9 11 26 57
        White
    		 230 224 220 671 1345
        More than one race
    		 0 5 2 8 15
        Unknown or Not Reported
    		 0 0 0 0 0
    Region of Enrollment
    Units: Subjects
        Argentina
    		 70 70 70 207 417
        Belgium
    		 0 1 0 1 2
        Brazil
    		 47 47 46 141 281
        Czechia
    		 10 9 9 29 57
        Germany
    		 7 8 8 24 47
        Greece
    		 2 2 2 9 15
        Hungary
    		 4 4 2 9 19
        Italy
    		 1 2 1 2 6
        Mexico
    		 19 20 20 59 118
        Romania
    		 14 14 12 38 78
        Russia
    		 19 17 19 52 107
        Slovakia
    		 16 13 15 39 83
        Spain
    		 5 3 3 14 25
        Turkey
    		 1 0 1 2 4
        United States
    		 28 28 28 85 169
    Hemoglobin A1c
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.
    Units: Percentage of HbA1c
        arithmetic mean (standard deviation)
    		 8.89 ± 0.97 8.78 ± 0.98 8.74 ± 1.01 8.81 ± 0.96 -

    End points

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    End points reporting groups
    Reporting group title
    5 mg Tirzepatide
    Reporting group description
    		 Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

    Reporting group title
    10 mg Tirzepatide
    Reporting group description
    		 Participants received 10 mg tirzepatide administered SC once a week.

    Reporting group title
    15 mg Tirzepatide
    Reporting group description
    		 Participants received 15 mg tirzepatide administered SC once a week.

    Reporting group title
    Insulin Lispro
    Reporting group description
    		 Participants received Insulin lispro 100 units per milliliter (U100) administered SC three times a day.

    Subject analysis set title
    Pooled 5 mg/10 mg/15 mg Tirzepatide
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received either 5 mg or 10 mg or 15 mg tirzepatide administered SC once a week.

    Primary: Change from Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg)

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    End point title
    		 Change from Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) [1]
    End point description
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares). Analysis Population Description (APD): All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
    End point type
    Primary
    End point timeframe
    Baseline, Week 52
    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: As per planned analysis, the endpoint was assessed for Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg.
    End point values
    		 Insulin Lispro Pooled 5 mg/10 mg/15 mg Tirzepatide
    Number of subjects analysed
    692
    708
    Units: Percentage of HbA1c
        least squares mean (standard error)
    -1.16 ± 0.049
    -2.26 ± 0.048
    Statistical analysis title
    		 Outcome measure 1
    Comparison groups
    Insulin Lispro v Pooled 5 mg/10 mg/15 mg Tirzepatide
    Number of subjects included in analysis
    1400
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.24
         upper limit
    		 -0.97
    Notes
    [2] - 0.3% noninferiority margin.

    Secondary: Change from Baseline in HbA1c

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    End point title
    		 Change from Baseline in HbA1c
    End point description
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    241
    234
    233
    692
    Units: Percentage of HbA1c
        least squares mean (standard error)
    -2.05 ± 0.082
    -2.27 ± 0.083
    -2.46 ± 0.084
    -1.16 ± 0.049
    Statistical analysis title
    		 Outcome measure 2
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    933
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.08
         upper limit
    		 -0.7
    Notes
    [3] - 0.3% noninferiority margin.
    Statistical analysis title
    		 Outcome measure 2
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    926
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 -0.92
    Notes
    [4] - 0.3% noninferiority margin.
    Statistical analysis title
    		 Outcome measure 2
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    925
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.49
         upper limit
    		 -1.11
    Notes
    [5] - 0.3% noninferiority margin.

    Secondary: Percentage of Participants with HbA1c Target Values <7.0%

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    End point title
    		 Percentage of Participants with HbA1c Target Values <7.0%
    End point description
    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    242
    238
    236
    708
    Units: Percentage of participants
        number (not applicable)
    61.04
    75.64
    79.86
    36.69
    Statistical analysis title
    		 Outcome measure 3
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    950
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.25
         upper limit
    		 4.36
    Statistical analysis title
    		 Outcome measure 3
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    946
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    6.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.27
         upper limit
    		 8.88
    Statistical analysis title
    		 Outcome measure 3
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    944
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    7.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.37
         upper limit
    		 11.75

    Secondary: Change from Baseline in Body Weight

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    End point title
    		 Change from Baseline in Body Weight
    End point description
    LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    241
    234
    233
    694
    Units: Kilograms (kg)
        least squares mean (standard error)
    -6.9 ± 0.37
    -9.9 ± 0.37
    -12.0 ± 0.38
    3.8 ± 0.22
    Statistical analysis title
    		 Outcome measure 4
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    935
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -10.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.5
         upper limit
    		 -9.9
    Statistical analysis title
    		 Outcome measure 4
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    928
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -13.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.5
         upper limit
    		 -12.9
    Statistical analysis title
    		 Outcome measure 4
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    927
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -15.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.7
         upper limit
    		 -15

    Secondary: Change from Baseline in Fasting Serum Glucose

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    End point title
    		 Change from Baseline in Fasting Serum Glucose
    End point description
    LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline metformin Use (Yes, No) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    241
    235
    233
    694
    Units: milligram per Deciliter (mg/dL)
        least squares mean (standard error)
    -33.2 ± 3.28
    -43.0 ± 3.32
    -41.6 ± 3.42
    -10.0 ± 1.99
    Statistical analysis title
    		 Outcome measure 5
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    935
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -23.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.8
         upper limit
    		 -15.7
    Statistical analysis title
    		 Outcome measure 5
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    929
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.6
         upper limit
    		 -25.4
    Statistical analysis title
    		 Outcome measure 5
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    927
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -31.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.3
         upper limit
    		 -23.8

    Secondary: Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

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    End point title
    		 Change from Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
    End point description
    The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post meal, Midday Premeal, Midday 2-hour Post meal, Evening Premeal, Evening 2-hour Post meal and Bedtime. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    219
    210
    204
    574
    Units: mg/dL/day
        least squares mean (standard error)
    -56.7 ± 1.80
    -61.5 ± 1.85
    67.6 ± 1.86
    -55.8 ± 1.13
    Statistical analysis title
    		 Outcome measure 6
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    793
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.682
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 3.3
    Statistical analysis title
    		 Outcome measure 6
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    784
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.01
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -5.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.9
         upper limit
    		 -1.4
    Statistical analysis title
    		 Outcome measure 6
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -11.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16
         upper limit
    		 -7.5

    Secondary: Percentage of Participants who Achieved HbA1c Target Value of <7.0% without Hypoglycemia

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    End point title
    		 Percentage of Participants who Achieved HbA1c Target Value of <7.0% without Hypoglycemia
    End point description
    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    241
    234
    233
    692
    Units: Percentage of HbA1c
        number (not applicable)
    52.70
    70.05
    75.12
    13.41
    Statistical analysis title
    		 Outcome measure 7
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    933
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    8.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.66
         upper limit
    		 11.83
    Statistical analysis title
    		 Outcome measure 7
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    926
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    16.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.44
         upper limit
    		 24.96
    Statistical analysis title
    		 Outcome measure 7
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    925
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    21.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.49
         upper limit
    		 32.93

    Secondary: Percentage of Participants who Achieved Weight Loss ≥5%

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    End point title
    		 Percentage of Participants who Achieved Weight Loss ≥5%
    End point description
    Percentage of Participants who Achieved Weight Loss ≥5% is reported here. APD: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    242
    238
    236
    708
    Units: Percentage of participants
        number (not applicable)
    64.19
    79.21
    83.15
    6.34
    Statistical analysis title
    		 Outcome measure 8
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    950
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    28.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.36
         upper limit
    		 43.46
    Statistical analysis title
    		 Outcome measure 8
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    946
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    58.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 36.76
         upper limit
    		 94.39
    Statistical analysis title
    		 Outcome measure 8
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    944
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    77.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 47.49
         upper limit
    		 127.33

    Secondary: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

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    End point title
    		 Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score
    End point description
    The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. PCS score is reported here. PCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by analysis of covariance (ANCOVA) model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    222
    217
    199
    599
    Units: score on a scale
        least squares mean (standard error)
    1.0 ± 0.46
    1.7 ± 0.46
    1.7 ± 0.48
    -0.6 ± 0.28
    Statistical analysis title
    		 Outcome measure 9
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    821
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 2.6
    Statistical analysis title
    		 Outcome measure 9
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    816
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 3.3
    Statistical analysis title
    		 Outcome measure 9
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    798
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 3.3

    Secondary: Change from Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score

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    End point title
    		 Change from Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score
    End point description
    The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. MCS score is reported here. MCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by ANCOVA model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment (Type III sum of squares). APD: All randomly assigned participants who took at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 5 mg Tirzepatide 10 mg Tirzepatide 15 mg Tirzepatide Insulin Lispro
    Number of subjects analysed
    222
    217
    199
    599
    Units: score on a scale
        least squares mean (standard error)
    0.3 ± 0.59
    1.5 ± 0.59
    0.7 ± 0.62
    -1.3 ± 0.36
    Statistical analysis title
    		 Outcome measure 10
    Comparison groups
    5 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    821
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 2.9
    Statistical analysis title
    		 Outcome measure 10
    Comparison groups
    10 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    816
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.5
         upper limit
    		 4.2
    Statistical analysis title
    		 Outcome measure 10
    Comparison groups
    15 mg Tirzepatide v Insulin Lispro
    Number of subjects included in analysis
    798
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 3.5

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to week 56
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    5 mg Tirzepatide
    Reporting group description
    		 Participants received 5 mg tirzepatide administered SC once a week

    Reporting group title
    Insulin Lispro
    Reporting group description
    		 Participants received Insulin lispro (U100) administered SC three times a day.

    Reporting group title
    15 mg Tirzepatide
    Reporting group description
    		 Participants received 15 mg tirzepatide administered SC once a week.

    Reporting group title
    10 mg Tirzepatide
    Reporting group description
    		 Participants received 10 mg tirzepatide administered SC once a week.

    Serious adverse events
    		 5 mg Tirzepatide Insulin Lispro 15 mg Tirzepatide 10 mg Tirzepatide
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 243 (8.23%)
    81 / 708 (11.44%)
    17 / 236 (7.20%)
    16 / 238 (6.72%)
         number of deaths (all causes)
    3
    11
    1
    3
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    adenocarcinoma of colon
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    breast cancer
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    glioblastoma
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    lipoma
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    oral neoplasm
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lung neoplasm malignant
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    2 / 708 (0.28%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    small cell lung cancer
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    giant cell arteritis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral arterial occlusive disease
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral ischaemia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral vascular disorder
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    aortic valve replacement
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    arthrodesis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery bypass
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    retinal cryoablation
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    umbilical hernia repair
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    abortion spontaneous
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed [1]
    1 / 144 (0.69%)
    0 / 396 (0.00%)
    0 / 133 (0.00%)
    0 / 149 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    death
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    hypothermia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    pulmonary embolism
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    pulmonary mass
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    2 / 708 (0.28%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary oedema
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    respiratory failure
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Psychiatric disorders
    bipolar disorder
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    mental status changes
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    suicide attempt
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    spinal fracture
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal compression fracture
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    skull fracture
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute coronary syndrome
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    angina unstable
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    3 / 708 (0.42%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    arteriosclerosis coronary artery
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    acute myocardial infarction
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    2 / 708 (0.28%)
    0 / 236 (0.00%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    atrial fibrillation
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac failure
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac failure congestive
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    3 / 708 (0.42%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial ischaemia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    3 / 708 (0.42%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    cerebrovascular accident
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebellar infarction
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    hypoglycaemic unconsciousness
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    2 / 708 (0.28%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypoglycaemic coma
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    2 / 708 (0.28%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    2 / 236 (0.85%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    iron deficiency anaemia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    colonic fistula
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    diverticulum intestinal haemorrhagic
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diabetic gastropathy
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lower gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholelithiasis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholecystitis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    diabetic foot
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    renal mass
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    inappropriate antidiuretic hormone secretion
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intervertebral disc protrusion
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    osteoarthritis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal disorder
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    appendicitis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bullous erysipelas
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    covid-19
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    7 / 708 (0.99%)
    2 / 236 (0.85%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    covid-19 pneumonia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    2 / 243 (0.82%)
    7 / 708 (0.99%)
    2 / 236 (0.85%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    gangrene
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    erysipelas
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    2 / 243 (0.82%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diabetic foot infection
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    2 / 708 (0.28%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cystitis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diabetic gangrene
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    infected skin ulcer
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    osteomyelitis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    oophoritis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed [2]
    0 / 144 (0.00%)
    1 / 396 (0.25%)
    0 / 133 (0.00%)
    0 / 149 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    postoperative abscess
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    1 / 708 (0.14%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    2 / 236 (0.85%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    septic shock
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    0 / 236 (0.00%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    1 / 243 (0.41%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    hyperkalaemia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    0 / 243 (0.00%)
    0 / 708 (0.00%)
    1 / 236 (0.42%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypoglycaemia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    2 / 243 (0.82%)
    28 / 708 (3.95%)
    1 / 236 (0.42%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    1 / 2
    25 / 84
    0 / 1
    1 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 5 mg Tirzepatide Insulin Lispro 15 mg Tirzepatide 10 mg Tirzepatide
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    94 / 243 (38.68%)
    99 / 708 (13.98%)
    121 / 236 (51.27%)
    116 / 238 (48.74%)
    Gastrointestinal disorders
    constipation
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    6 / 243 (2.47%)
    4 / 708 (0.56%)
    14 / 236 (5.93%)
    8 / 238 (3.36%)
         occurrences all number
    9
    9
    19
    8
    vomiting
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    11 / 243 (4.53%)
    4 / 708 (0.56%)
    30 / 236 (12.71%)
    21 / 238 (8.82%)
         occurrences all number
    14
    4
    80
    35
    dyspepsia
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    15 / 243 (6.17%)
    4 / 708 (0.56%)
    27 / 236 (11.44%)
    27 / 238 (11.34%)
         occurrences all number
    16
    4
    34
    47
    nausea
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    33 / 243 (13.58%)
    8 / 708 (1.13%)
    61 / 236 (25.85%)
    49 / 238 (20.59%)
         occurrences all number
    71
    11
    161
    80
    diarrhoea
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    29 / 243 (11.93%)
    17 / 708 (2.40%)
    26 / 236 (11.02%)
    36 / 238 (15.13%)
         occurrences all number
    46
    22
    49
    66
    Infections and infestations
    covid-19
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    28 / 243 (11.52%)
    72 / 708 (10.17%)
    21 / 236 (8.90%)
    19 / 238 (7.98%)
         occurrences all number
    28
    73
    23
    19
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 25.1
         subjects affected / exposed
    20 / 243 (8.23%)
    1 / 708 (0.14%)
    40 / 236 (16.95%)
    28 / 238 (11.76%)
         occurrences all number
    81
    1
    128
    84

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Jan 2021
    Protocol Amendment (b): Section 10.9. Appendix 9: An appendix was added describing the temporary measures intended to be used only in the case of exceptional circumstances during specific time periods as directed by the sponsor in partnership with the investigator. Section 5.2. Exclusion Criteria: Section 10.1.5 10.1.10; 1.2 Schema, Section 6.5: Minor errors in units, section numbering, abbreviations, and incorrect references were corrected.

    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
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