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    Clinical Trial Results:
    Empagliflozin as a Modulator of Systemic Vascular Resistance and Cardiac Output in Patients with Type 2 Diabetes

    Summary
    EudraCT number
    		 2016-000172-19
    Trial protocol
    		 DE  
    Global end of trial date
    23 Jan 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Oct 2021
    First version publication date
    30 Oct 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    15-124
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03132181
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    RWTH Aachen University for the Medical Faculty, represented by Center for Translational & Clinical Research Aachen (CTC-A)
    Sponsor organisation address
    Pauwelsstraße 30, Aachen, Germany, 52074
    Public contact
    Center for Translational & Clinical Research Aachen (CTC-A), RWTH Aachen University, +49 2418080092, ctc-a-sekretariat@ukaachen.de
    Scientific contact
    Center for Translational & Clinical Research Aachen (CTC-A), RWTH Aachen University, +49 2418080092, ctc-a-sekretariat@ukaachen.de
    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
    29 May 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Jan 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Jan 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Effect of empagliflozin 10 mg once daily on cardiac output in comparison to placebo after 1 day, 3 days and 12 weeks of treatment (measured with a noninvasive monitoring [ClearSight System]).
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation of Good Clinical Practice, the principles of the Declaration of Helsinki, as well as other applicable local ethical and legal requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 May 2017
    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
    Germany: 44
    Worldwide total number of subjects
    44
    EEA total number of subjects
    44
    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)
    27
    From 65 to 84 years
    17
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Recruitment and treatment of subjects was performed in one trial center. Overall 44 subjects were enrolled and randomized in the clinical trial in the timeframe from 02.05.2017 till 22.10.2018.

    Pre-assignment
    Screening details
    		 Overall 55 subjects were screened in one trial center. Of those 55 subjects screened, 44 subjects met the inclusion and exclusion criteria and were enrolled and randomized in the clinical trial.

    Period 1
    Period 1 title
    Baseline visit
    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
    		 Empagliflozin
    Arm description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Empagliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg tablets once daily administered orally

    Arm title
    		 Placebo
    Arm description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One tablet daily administered orally

    Number of subjects in period 1
    		Empagliflozin Placebo
    Started
    22
    22
    Completed
    22
    22
    Period 2
    Period 2 title
    Day 1
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Empagliflozin
    Arm description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Empagliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg tablets once daily administered orally

    Arm title
    		 Placebo
    Arm description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One tablet daily administered orally

    Number of subjects in period 2
    		Empagliflozin Placebo
    Started
    22
    22
    Completed
    22
    22
    Period 3
    Period 3 title
    Day 3
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Empagliflozin
    Arm description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Empagliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg tablets once daily administered orally

    Arm title
    		 Placebo
    Arm description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One tablet daily administered orally

    Number of subjects in period 3
    		Empagliflozin Placebo
    Started
    22
    22
    Completed
    21
    22
    Not completed
    1
    0
         Adverse event, non-fatal
    1
    -
    Period 4
    Period 4 title
    3 Months
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Empagliflozin
    Arm description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Empagliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg tablets once daily administered orally

    Arm title
    		 Placebo
    Arm description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One tablet daily administered orally

    Number of subjects in period 4
    		Empagliflozin Placebo
    Started
    21
    22
    Completed
    20
    22
    Not completed
    1
    0
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Empagliflozin
    Reporting group description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.

    Reporting group values
    		 Empagliflozin Placebo Total
    Number of subjects
    		 22 22 44
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.4 ( 5.4 ) 61.2 ( 7.9 ) -
    Gender categorical
    Units: Subjects
        Female
    		 5 4 9
        Male
    		 17 18 35
    Type 2 diabetes - Insulin treated
    Units: Subjects
        yes
    		 12 8 20
        no
    		 10 14 24
    Type 2 diabetes - Metformin treatment
    Units: Subjects
        yes
    		 14 18 32
        no
    		 8 4 12
    Type 2 diabetes - DPP-4 inhibitor treatment
    Units: Subjects
        yes
    		 8 6 14
        no
    		 14 16 30
    Type 2 diabetes - other treatments
    Units: Subjects
        yes
    		 3 1 4
        no
    		 19 21 40
    History of CVD - coronary heart disease
    Units: Subjects
        yes
    		 17 15 32
        no
    		 5 7 12
    History of CVD - myocardial infarction
    Units: Subjects
        yes
    		 6 10 16
        no
    		 16 12 28
    History of CVD - CABG
    Units: Subjects
        yes
    		 5 4 9
        no
    		 17 18 35
    History of CVD - PCI
    Units: Subjects
        yes
    		 11 12 23
        no
    		 11 10 21
    History of CVD - Peripheral artery disease
    Units: Subjects
        yes
    		 4 2 6
        no
    		 18 20 38
    Chronic heart failure
    Units: Subjects
        yes
    		 7 11 18
        no
    		 15 11 26
    Medication - antiplatelets
    Units: Subjects
        yes
    		 13 16 29
        no
    		 9 6 15
    Medication - Oral anticoagulants
    Units: Subjects
        yes
    		 6 5 11
        no
    		 16 17 33
    Medication - Diuretics
    Units: Subjects
        yes
    		 10 10 20
        no
    		 12 12 24
    Medication - Statins
    Units: Subjects
        yes
    		 17 15 32
        no
    		 5 7 12
    Medication - Calcium channel blockers
    Units: Subjects
        yes
    		 4 5 9
        no
    		 18 17 35
    Medication - Beta blockers
    Units: Subjects
        yes
    		 18 16 34
        no
    		 4 6 10
    Medication - RAAS inhibitors
    Units: Subjects
        yes
    		 16 20 36
        no
    		 6 2 8
    Body mass index
    Units: kg/m²
        arithmetic mean (standard deviation)
    		 31.7 ( 5.2 ) 31.2 ( 4.0 ) -
    Systolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    		 136 ( 16 ) 136 ( 18 ) -
    Diastolic blood pressure
    Units: mmHg
        arithmetic mean (standard deviation)
    		 83 ( 14 ) 81 ( 14 ) -
    Heart rate
    Units: bpm
        arithmetic mean (standard deviation)
    		 71 ( 12 ) 69 ( 15 ) -
    Type 2 diabetes - glycated hemoglobin
    Units: percentage
        arithmetic mean (standard deviation)
    		 7.5 ( 0.8 ) 8.0 ( 1.2 ) -
    Type 2 diabetes - diabetes duration
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 10 (3 to 13) 9 (6 to 18) -
    eGFR
    Units: ml/min/1.73m²
        arithmetic mean (standard deviation)
    		 78 ( 20 ) 88 ( 16 ) -
    Total cholesterol
    Units: mg/dl
        arithmetic mean (standard deviation)
    		 168 ( 39 ) 155 ( 39 ) -
    LDL-C
    Units: mg/dl
        arithmetic mean (standard deviation)
    		 101 ( 35 ) 95 ( 38 ) -
    HDL-C
    Units: mg/dl
        arithmetic mean (standard deviation)
    		 43 ( 9 ) 44 ( 9 ) -
    Triglycerides
    Units: mg/dl
        arithmetic mean (standard deviation)
    		 247 ( 147 ) 156 ( 71 ) -

    End points

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    End points reporting groups
    Reporting group title
    Empagliflozin
    Reporting group description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.
    Reporting group title
    Empagliflozin
    Reporting group description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.
    Reporting group title
    Empagliflozin
    Reporting group description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.
    Reporting group title
    Empagliflozin
    Reporting group description
    		 Subjects in the Empagliflozin arm receive 10 mg tablets Empagliflozin once daily for 3 months.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects in the Placebo arm receive one tablet once daily for 3 months.

    Primary: Systemic vascular resistance index - Baseline

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    End point title
    		 Systemic vascular resistance index - Baseline
    End point description
    End point type
    Primary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [1]
    22
    Units: dyne*sec*cm^(-5)*m^(-2)
        arithmetic mean (standard deviation)
    1841 ( 379 )
    1836 ( 361 )
    Notes
    [1] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis SVRI - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.967
    Method
    		 Wald test
    Confidence interval

    Primary: Systemic vascular resistance index - Day 1

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    End point title
    		 Systemic vascular resistance index - Day 1
    End point description
    End point type
    Primary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [2]
    22
    Units: dyne*sec*cm^(-5)*m^(-2)
        arithmetic mean (standard deviation)
    1864 ( 373 )
    1942 ( 355 )
    Notes
    [2] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis SVRI - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.411
    Method
    		 Wald test
    Confidence interval

    Primary: Systemic vascular resistance index - Day 3

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    End point title
    		 Systemic vascular resistance index - Day 3
    End point description
    End point type
    Primary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [3]
    22
    Units: dyne*sec*cm^(-5)*m^(-2)
        arithmetic mean (standard deviation)
    1837 ( 376 )
    1831 ( 310 )
    Notes
    [3] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis SVRI - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.991
    Method
    		 Wald test
    Confidence interval

    Primary: Systemic vascular resistance index - 3 Months

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    End point title
    		 Systemic vascular resistance index - 3 Months
    End point description
    End point type
    Primary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [4]
    22
    Units: dyne*sec*cm^(-5)*m^(-2)
        arithmetic mean (standard deviation)
    1908 ( 451 )
    1909 ( 428 )
    Notes
    [4] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    Statistical analysis title
    		 Analysis SVRI - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.795
    Method
    		 Wald test
    Confidence interval

    Primary: Cardiac index - Baseline

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    End point title
    		 Cardiac index - Baseline
    End point description
    End point type
    Primary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [5]
    22
    Units: l/min/m²
        arithmetic mean (standard deviation)
    3.2 ( 0.6 )
    3.2 ( 0.6 )
    Notes
    [5] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis CI - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.682
    Method
    		 Wald test
    Confidence interval

    Primary: Cardiac index - Day 1

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    End point title
    		 Cardiac index - Day 1
    End point description
    End point type
    Primary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [6]
    22
    Units: l/min/m²
        arithmetic mean (standard deviation)
    3.1 ( 0.5 )
    3.1 ( 0.5 )
    Notes
    [6] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis CI - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.771
    Method
    		 Wald test
    Confidence interval

    Primary: Cardiac index - Day 3

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    End point title
    		 Cardiac index - Day 3
    End point description
    End point type
    Primary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [7]
    22
    Units: l/min/m²
        arithmetic mean (standard deviation)
    3.0 ( 0.6 )
    3.1 ( 0.5 )
    Notes
    [7] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis CI - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.293
    Method
    		 Wald test
    Confidence interval

    Primary: Cardiac index - 3 Months

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    End point title
    		 Cardiac index - 3 Months
    End point description
    End point type
    Primary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [8]
    22
    Units: l/min/m²
        arithmetic mean (standard deviation)
    3.1 ( 0.5 )
    3.1 ( 0.5 )
    Notes
    [8] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    Statistical analysis title
    		 Analysis CI - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.303
    Method
    		 Wald test
    Confidence interval

    Secondary: Heart rate - Baseline

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    End point title
    		 Heart rate - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [9]
    22
    Units: bpm
        arithmetic mean (standard deviation)
    68 ( 12 )
    66 ( 13 )
    Notes
    [9] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis HR - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.665
    Method
    		 Wald test
    Confidence interval

    Secondary: Heart rate - Day 1

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    End point title
    		 Heart rate - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [10]
    22
    Units: bpm
        arithmetic mean (standard deviation)
    69 ( 13 )
    65 ( 11 )
    Notes
    [10] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis HR - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.122
    Method
    		 Wald test
    Confidence interval

    Secondary: Heart rate - Day 3

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    End point title
    		 Heart rate - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [11]
    22
    Units: bpm
        arithmetic mean (standard deviation)
    68 ( 14 )
    66 ( 11 )
    Notes
    [11] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis HR - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.717
    Method
    		 Wald test
    Confidence interval

    Secondary: Heart rate - 3 Months

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    End point title
    		 Heart rate - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [12]
    22
    Units: bpm
        arithmetic mean (standard deviation)
    67 ( 10 )
    66 ( 11 )
    Notes
    [12] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    Statistical analysis title
    		 Analysis HR - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.393
    Method
    		 Wald test
    Confidence interval

    Secondary: Systolic blood pressure - Baseline

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    End point title
    		 Systolic blood pressure - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [13]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    135 ( 16 )
    136 ( 18 )
    Notes
    [13] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis syst. BP - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.934
    Method
    		 Wald test
    Confidence interval

    Secondary: Systolic blood pressure - Day 1

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    End point title
    		 Systolic blood pressure - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [14]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    128 ( 16 )
    134 ( 16 )
    Notes
    [14] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis syst. BP - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.279
    Method
    		 Wald test
    Confidence interval

    Secondary: Systolic blood pressure - Day 3

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    End point title
    		 Systolic blood pressure - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [15]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    125 ( 16 )
    133 ( 19 )
    Notes
    [15] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis syst. BP - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.115
    Method
    		 Wald test
    Confidence interval

    Secondary: Systolic blood pressure - 3 Months

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    End point title
    		 Systolic blood pressure - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    16 [16]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    128 ( 15 )
    132 ( 20 )
    Notes
    [16] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
    Statistical analysis title
    		 Analysis syst. BP - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.318
    Method
    		 Wald test
    Confidence interval

    Secondary: Diastolic blood pressure - Baseline

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    End point title
    		 Diastolic blood pressure - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [17]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    82 ( 13 )
    81 ( 14 )
    Notes
    [17] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis diast. BP - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.964
    Method
    		 Wald test
    Confidence interval

    Secondary: Diastolic blood pressure - Day 1

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    End point title
    		 Diastolic blood pressure - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [18]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    80 ( 11 )
    80 ( 13 )
    Notes
    [18] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis diast. BP - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.876
    Method
    		 Wald test
    Confidence interval

    Secondary: Diastolic blood pressure - Day 3

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    End point title
    		 Diastolic blood pressure - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [19]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    80 ( 9 )
    80 ( 12 )
    Notes
    [19] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis diast. BP - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.925
    Method
    		 Wald test
    Confidence interval

    Secondary: Diastolic blood pressure - 3 Months

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    End point title
    		 Diastolic blood pressure - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    16 [20]
    22
    Units: mmHg
        arithmetic mean (standard deviation)
    79 ( 11 )
    82 ( 11 )
    Notes
    [20] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
    Statistical analysis title
    		 Analysis diast. BP - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.197
    Method
    		 Wald test
    Confidence interval

    Secondary: Stroke volume index - Baseline

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    End point title
    		 Stroke volume index - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [21]
    22
    Units: ml/b/m²
        arithmetic mean (standard deviation)
    47 ( 7 )
    50 ( 7 )
    Notes
    [21] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis SVI - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.266
    Method
    		 Wald test
    Confidence interval

    Secondary: Stroke volume index - Day 1

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    End point title
    		 Stroke volume index - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [22]
    22
    Units: ml/b/m²
        arithmetic mean (standard deviation)
    45 ( 8 )
    48 ( 8 )
    Notes
    [22] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis SVI - Day 1
    Comparison groups
    Placebo v Empagliflozin
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.344
    Method
    		 Wald test
    Confidence interval

    Secondary: Stroke volume index - Day 3

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    End point title
    		 Stroke volume index - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [23]
    22
    Units: ml/b/m²
        arithmetic mean (standard deviation)
    44 ( 8 )
    48 ( 8 )
    Notes
    [23] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis SVI - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.131
    Method
    		 Wald test
    Confidence interval

    Secondary: Stroke volume index - 3 Months

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    End point title
    		 Stroke volume index - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [24]
    22
    Units: ml/b/m²
        arithmetic mean (standard deviation)
    47 ( 7 )
    47 ( 7 )
    Notes
    [24] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    Statistical analysis title
    		 Analysis SVI - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.879
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular ejection fraction - Baseline

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    End point title
    		 Left ventricular ejection fraction - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [25]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    51 ( 5.0 )
    48 ( 6.8 )
    Notes
    [25] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LV-EF - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.183
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular ejection fraction - Day 1

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    End point title
    		 Left ventricular ejection fraction - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [26]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    51 ( 4.6 )
    48 ( 6.2 )
    Notes
    [26] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LV-EF - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.852
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular ejection fraction - Day 3

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    End point title
    		 Left ventricular ejection fraction - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [27]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    51 ( 4.7 )
    48 ( 6.1 )
    Notes
    [27] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LV-EF - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.333
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular ejection fraction - 3 Months

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    End point title
    		 Left ventricular ejection fraction - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [28]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    51 ( 4.4 )
    48 ( 6.4 )
    Notes
    [28] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LV-EF - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.375
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular diastolic function (E/é mean) - Baseline

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    End point title
    		 Left ventricular diastolic function (E/é mean) - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [29]
    21 [30]
    Units: none
        arithmetic mean (standard deviation)
    9.2 ( 2.6 )
    9.3 ( 2.2 )
    Notes
    [29] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [30] - 1 missing data
    Statistical analysis title
    		 Analysis E/é mean - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.898
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular diastolic function (E/é mean) - Day 1

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    End point title
    		 Left ventricular diastolic function (E/é mean) - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [31]
    22
    Units: none
        arithmetic mean (standard deviation)
    8.5 ( 2.2 )
    10.1 ( 1.4 )
    Notes
    [31] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis E/é mean - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular diastolic function (E/é mean) - Day 3

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    End point title
    		 Left ventricular diastolic function (E/é mean) - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [32]
    22
    Units: none
        arithmetic mean (standard deviation)
    8.5 ( 2.4 )
    9.5 ( 1.5 )
    Notes
    [32] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis E/é mean - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.079
    Method
    		 Wald test
    Confidence interval

    Secondary: Left ventricular diastolic function (E/é mean) - 3 Months

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    End point title
    		 Left ventricular diastolic function (E/é mean) - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [33]
    22
    Units: none
        arithmetic mean (standard deviation)
    8.3 ( 2.9 )
    9.7 ( 1.9 )
    Notes
    [33] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    Statistical analysis title
    		 Analysis E/é mean - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 Wald test
    Confidence interval

    Secondary: Left atrial volume index - Baseline

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    End point title
    		 Left atrial volume index - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [34]
    22
    Units: ml/m²
        arithmetic mean (standard deviation)
    28 ( 9 )
    31 ( 11 )
    Notes
    [34] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LA VI - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.414
    Method
    		 Wald test
    Confidence interval

    Secondary: Left atrial volume index - Day 1

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    End point title
    		 Left atrial volume index - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [35]
    22
    Units: ml/m²
        arithmetic mean (standard deviation)
    26 ( 10 )
    30 ( 13 )
    Notes
    [35] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LA VI - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3
    Method
    		 Wald test
    Confidence interval

    Secondary: Left atrial volume index - Day 3

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    End point title
    		 Left atrial volume index - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [36]
    22
    Units: ml/m²
        arithmetic mean (standard deviation)
    28 ( 10 )
    30 ( 13 )
    Notes
    [36] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LA VI - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.84
    Method
    		 Wald test
    Confidence interval

    Secondary: Left atrial volume index - 3 Months

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    End point title
    		 Left atrial volume index - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [37]
    22
    Units: ml/m²
        arithmetic mean (standard deviation)
    26 ( 9 )
    31 ( 12 )
    Notes
    [37] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LA VI - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.239
    Method
    		 Wald test
    Confidence interval

    Secondary: Mitral E-wave velocity - Baseline

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    End point title
    		 Mitral E-wave velocity - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [38]
    21 [39]
    Units: m/sec
        arithmetic mean (standard deviation)
    0.80 ( 0.20 )
    0.78 ( 0.14 )
    Notes
    [38] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [39] - 1 missing data
    Statistical analysis title
    		 Analysis E - Baseline
    Comparison groups
    Placebo v Empagliflozin
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.686
    Method
    		 Wald test
    Confidence interval

    Secondary: Mitral E-wave velocity - Day 1

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    End point title
    		 Mitral E-wave velocity - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [40]
    22
    Units: m/sec
        arithmetic mean (standard deviation)
    0.73 ( 0.20 )
    0.80 ( 0.12 )
    Notes
    [40] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis E - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Wald test
    Confidence interval

    Secondary: Mitral E-wave velocity - Day 3

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    End point title
    		 Mitral E-wave velocity - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [41]
    22
    Units: m/sec
        arithmetic mean (standard deviation)
    0.72 ( 0.18 )
    0.78 ( 0.11 )
    Notes
    [41] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis E - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005
    Method
    		 Wald test
    Confidence interval

    Secondary: Mitral E-wave velocity - 3 Months

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    End point title
    		 Mitral E-wave velocity - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [42]
    22
    Units: m/sec
        arithmetic mean (standard deviation)
    0.72 ( 0.21 )
    0.78 ( 0.13 )
    Notes
    [42] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    Statistical analysis title
    		 Analysis E - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose serum level - Baseline

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    End point title
    		 Glucose serum level - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [43]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    181 ( 75 )
    175 ( 52 )
    Notes
    [43] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Glucose - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.742
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose serum level - Day 1

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    End point title
    		 Glucose serum level - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [44]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    152 ( 38 )
    171 ( 48 )
    Notes
    [44] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Glucose - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose serum level - Day 3

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    End point title
    		 Glucose serum level - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [45]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    146 ( 35 )
    166 ( 52 )
    Notes
    [45] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis Glucose - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.037
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose serum level - 3 Months

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    End point title
    		 Glucose serum level - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [46]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    150 ( 41 )
    156 ( 52 )
    Notes
    [46] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis Glucose - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.754
    Method
    		 Wald test
    Confidence interval

    Secondary: HbA1c serum level - Baseline

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    End point title
    		 HbA1c serum level - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [47]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    7.5 ( 0.9 )
    7.9 ( 1.3 )
    Notes
    [47] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis HbA1c - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.228
    Method
    		 Wald test
    Confidence interval

    Secondary: HbA1c serum leven - Day 1

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    End point title
    		 HbA1c serum leven - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [48]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    7.4 ( 0.9 )
    7.9 ( 1.3 )
    Notes
    [48] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis HbA1c - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.722
    Method
    		 Wald test
    Confidence interval

    Secondary: HbA1c serum level - Day 3

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    End point title
    		 HbA1c serum level - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [49]
    20 [50]
    Units: percentage
        arithmetic mean (standard deviation)
    7.4 ( 0.9 )
    7.9 ( 1.2 )
    Notes
    [49] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    [50] - 2 missing data
    Statistical analysis title
    		 Analysis HbA1c - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.69
    Method
    		 Wald test
    Confidence interval

    Secondary: HbA1c serum level - 3 Months

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    End point title
    		 HbA1c serum level - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [51]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    7.2 ( 0.7 )
    7.8 ( 1.5 )
    Notes
    [51] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis HbA1c - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.595
    Method
    		 Wald test
    Confidence interval

    Secondary: Cystatin C serum level - Baseline

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    End point title
    		 Cystatin C serum level - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [52]
    22
    Units: mg/l
        arithmetic mean (standard deviation)
    1.2 ( 0.4 )
    1.0 ( 0.2 )
    Notes
    [52] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Cystatin C - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.148
    Method
    		 Wald test
    Confidence interval

    Secondary: Cystatin C serum level - Day 1

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    End point title
    		 Cystatin C serum level - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [53]
    22
    Units: mg/l
        arithmetic mean (standard deviation)
    1.3 ( 0.4 )
    1.0 ( 0.2 )
    Notes
    [53] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Cystatin C - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Confidence interval

    Secondary: Cystatin C serum level - Day 3

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    End point title
    		 Cystatin C serum level - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [54]
    22
    Units: mg/l
        arithmetic mean (standard deviation)
    1.3 ( 0.4 )
    1.0 ( 0.2 )
    Notes
    [54] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis Cystatin C - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Wald test
    Confidence interval

    Secondary: Cystatin C serum level - 3 Months

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    End point title
    		 Cystatin C serum level - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [55]
    22
    Units: mg/l
        arithmetic mean (standard deviation)
    1.3 ( 0.4 )
    1.0 ( 0.2 )
    Notes
    [55] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis Cystatin C - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Confidence interval

    Secondary: NT-proBNP serum level - Baseline

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    End point title
    		 NT-proBNP serum level - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [56]
    22
    Units: pg/ml
        median (inter-quartile range (Q1-Q3))
    239 (91 to 463)
    166 (73 to 238)
    Notes
    [56] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis NT-proBNP - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.481
    Method
    		 Wald test
    Confidence interval

    Secondary: NT-proBNP serum level - Day 1

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    End point title
    		 NT-proBNP serum level - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [57]
    22
    Units: pg/ml
        median (inter-quartile range (Q1-Q3))
    192 (63 to 385)
    168 (67 to 252)
    Notes
    [57] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis NT-proBNP - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.224
    Method
    		 Wald test
    Confidence interval

    Secondary: NT-proBNP serum level - Day 3

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    End point title
    		 NT-proBNP serum level - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [58]
    22
    Units: pg/ml
        median (inter-quartile range (Q1-Q3))
    173 (57 to 402)
    147 (58 to 226)
    Notes
    [58] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis NT-proBNP - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.408
    Method
    		 Wald test
    Confidence interval

    Secondary: NT-proBNP serum level - 3 Months

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    End point title
    		 NT-proBNP serum level - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [59]
    20 [60]
    Units: pg/ml
        median (inter-quartile range (Q1-Q3))
    120 (34 to 356)
    158 (42 to 262)
    Notes
    [59] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    [60] - 2 missing data
    Statistical analysis title
    		 Analysis NT-proBNP - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.723
    Method
    		 Wald test
    Confidence interval

    Secondary: Aldosterone serum level - Baseline

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    End point title
    		 Aldosterone serum level - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [61]
    22
    Units: pg/ml
        arithmetic mean (standard deviation)
    104 ( 65 )
    83 ( 33 )
    Notes
    [61] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Aldosterone - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.213
    Method
    		 Wald test
    Confidence interval

    Secondary: Aldosterone serum level - Day 1

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    End point title
    		 Aldosterone serum level - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [62]
    22
    Units: pg/ml
        arithmetic mean (standard deviation)
    111 ( 67 )
    88 ( 32 )
    Notes
    [62] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Aldosterone - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.825
    Method
    		 Wald test
    Confidence interval

    Secondary: Aldosterone serum level - Day 3

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    End point title
    		 Aldosterone serum level - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [63]
    22
    Units: pg/ml
        arithmetic mean (standard deviation)
    108 ( 59 )
    96 ( 50 )
    Notes
    [63] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis Aldosterone - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.635
    Method
    		 Wald test
    Confidence interval

    Secondary: Aldosterone serum level - 3 Months

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    End point title
    		 Aldosterone serum level - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [64]
    22
    Units: pg/ml
        arithmetic mean (standard deviation)
    137 ( 104 )
    108 ( 71 )
    Notes
    [64] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis Aldosterone - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.522
    Method
    		 Wald test
    Confidence interval

    Secondary: Sodium urine excretion - Baseline

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    End point title
    		 Sodium urine excretion - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [65]
    20 [66]
    Units: mmol/24hrs
        arithmetic mean (standard deviation)
    164 ( 88 )
    196 ( 84 )
    Notes
    [65] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [66] - 2 missing data
    Statistical analysis title
    		 Analysis Sodium excretion - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.255
    Method
    		 Wald test
    Confidence interval

    Secondary: Sodium urine excretion - Day 1

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    End point title
    		 Sodium urine excretion - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [67]
    21 [68]
    Units: mmol/24hrs
        arithmetic mean (standard deviation)
    185 ( 111 )
    181 ( 76 )
    Notes
    [67] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [68] - 1 missing data
    Statistical analysis title
    		 Analysis Sodium excretion - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.223
    Method
    		 Wald test
    Confidence interval

    Secondary: Sodium urine excretion - Day 3

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    End point title
    		 Sodium urine excretion - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [69]
    21 [70]
    Units: mmol/24hrs
        arithmetic mean (standard deviation)
    181 ( 126 )
    203 ( 107 )
    Notes
    [69] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    [70] - 1 missing data
    Statistical analysis title
    		 Analysis Sodium excretion - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.97
    Method
    		 Wald test
    Confidence interval

    Secondary: Sodium urine excretion - 3 Months

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    End point title
    		 Sodium urine excretion - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    16 [71]
    20 [72]
    Units: mmol/24hrs
        arithmetic mean (standard deviation)
    201 ( 145 )
    175 ( 55 )
    Notes
    [71] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
    [72] - 2 missing data
    Statistical analysis title
    		 Analysis Sodium excretion - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.054
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose urine excretion - Baseline

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    End point title
    		 Glucose urine excretion - Baseline
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [73]
    20 [74]
    Units: g/24hrs
        arithmetic mean (standard deviation)
    7.3 ( 22.7 )
    10.9 ( 22.7 )
    Notes
    [73] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [74] - 2 missing data
    Statistical analysis title
    		 Analysis Glucose excretion - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.617
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose urine excretion - Day 1

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    End point title
    		 Glucose urine excretion - Day 1
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [75]
    21 [76]
    Units: g/24hrs
        arithmetic mean (standard deviation)
    48.4 ( 34.7 )
    6.9 ( 14.1 )
    Notes
    [75] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [76] - 1 missing data
    Statistical analysis title
    		 Analysis Glucose excretion - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose urine excretion - Day 3

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    End point title
    		 Glucose urine excretion - Day 3
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [77]
    21 [78]
    Units: g/24hrs
        arithmetic mean (standard deviation)
    65.7 ( 43.3 )
    7.5 ( 14.5 )
    Notes
    [77] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    [78] - 1 missing data
    Statistical analysis title
    		 Analysis Glucose excretion - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Confidence interval

    Secondary: Glucose urine excretion - 3 Months

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    End point title
    		 Glucose urine excretion - 3 Months
    End point description
    End point type
    Secondary
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    16 [79]
    20 [80]
    Units: g/24hrs
        arithmetic mean (standard deviation)
    67.6 ( 50.9 )
    10.2 ( 18.7 )
    Notes
    [79] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
    [80] - 2 missing data
    Statistical analysis title
    		 Analysis Glucose excretion - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Total cholesterol serum level - Baseline

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    End point title
    		 Total cholesterol serum level - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [81]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    169 ( 41 )
    155 ( 39 )
    Notes
    [81] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Total Cholesterol - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.257
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Total cholesterol serum level - Day 1

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    End point title
    		 Total cholesterol serum level - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [82]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    174 ( 43 )
    155 ( 37 )
    Notes
    [82] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Total Cholesterol - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.178
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Total cholesterol serum level - Day 3

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    End point title
    		 Total cholesterol serum level - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [83]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    168 ( 39 )
    152 ( 40 )
    Notes
    [83] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis Total Cholesterol - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.824
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Total cholesterol serum level - 3 Months

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    End point title
    		 Total cholesterol serum level - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [84]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    185 ( 48 )
    152 ( 42 )
    Notes
    [84] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis Total Cholesterol - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Wald test
    Confidence interval

    Post-hoc: LDL-C serum level - Baseline

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    End point title
    		 LDL-C serum level - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [85]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    103 ( 36 )
    95 ( 38 )
    Notes
    [85] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis LDL-C - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.522
    Method
    		 Wald test
    Confidence interval

    Post-hoc: LDL-C serum level - Day 1

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    End point title
    		 LDL-C serum level - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [86]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    102 ( 36 )
    94 ( 36 )
    Notes
    [86] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis LDL-C - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.915
    Method
    		 Wald test
    Confidence interval

    Post-hoc: LDL-C serum level - Day 3

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    End point title
    		 LDL-C serum level - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [87]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    102 ( 40 )
    93 ( 39 )
    Notes
    [87] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LDL-C - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.477
    Method
    		 Wald test
    Confidence interval

    Post-hoc: LDL-C serum level - 3 Months

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    End point title
    		 LDL-C serum level - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [88]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    112 ( 47 )
    89 ( 39 )
    Notes
    [88] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LDL-C - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Confidence interval

    Post-hoc: HDL-C serum level - Baseline

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    End point title
    		 HDL-C serum level - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [89]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    43 ( 9 )
    44 ( 9 )
    Notes
    [89] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis HDL-C - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.53
    Method
    		 Wald test
    Confidence interval

    Post-hoc: HDL-C serum level - Day 1

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    End point title
    		 HDL-C serum level - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [90]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    42 ( 10 )
    44 ( 9 )
    Notes
    [90] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis HDL-C - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.947
    Method
    		 Wald test
    Confidence interval

    Post-hoc: HDL-C serum level - Day 3

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    End point title
    		 HDL-C serum level - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [91]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    43 ( 9 )
    44 ( 9 )
    Notes
    [91] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis HDL-C - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.9
    Method
    		 Wald test
    Confidence interval

    Post-hoc: HDL-C serum level - 3 Months

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    End point title
    		 HDL-C serum level - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [92]
    22
    Units: mg/dl
        arithmetic mean (standard deviation)
    46 ( 10 )
    46 ( 11 )
    Notes
    [92] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis HDL-C - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.937
    Method
    		 Wald test
    Confidence interval

    Post-hoc: eGFR - Baseline

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    End point title
    		 eGFR - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [93]
    22
    Units: ml/min/1.73m²
        arithmetic mean (standard deviation)
    77 ( 21 )
    88 ( 16 )
    Notes
    [93] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis eGFR - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.076
    Method
    		 Wald test
    Confidence interval

    Post-hoc: eGFR - Day 1

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    End point title
    		 eGFR - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [94]
    22
    Units: ml/min/1.73m²
        arithmetic mean (standard deviation)
    70 ( 19 )
    85 ( 16 )
    Notes
    [94] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis eGFR - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.014
    Method
    		 Wald test
    Confidence interval

    Post-hoc: eGFR - Day 3

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    End point title
    		 eGFR - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [95]
    22
    Units: ml/min/1.73m²
        arithmetic mean (standard deviation)
    70 ( 21 )
    85 ( 17 )
    Notes
    [95] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis eGFR - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.039
    Method
    		 Wald test
    Confidence interval

    Post-hoc: eGFR - 3 Months

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    End point title
    		 eGFR - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [96]
    22
    Units: ml/min/1.73m²
        arithmetic mean (standard deviation)
    68 ( 20 )
    85 ( 16 )
    Notes
    [96] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis eGFR - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.108
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hemoglobin - Baseline

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    End point title
    		 Hemoglobin - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [97]
    22
    Units: g/dl
        arithmetic mean (standard deviation)
    13.7 ( 1.8 )
    14.3 ( 1.3 )
    Notes
    [97] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Hemoglobin - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.299
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hemoglobin - Day 1

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    End point title
    		 Hemoglobin - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [98]
    22
    Units: g/dl
        arithmetic mean (standard deviation)
    13.7 ( 1.9 )
    14.1 ( 1.2 )
    Notes
    [98] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Hemoglobin - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.487
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hemoglobin - Day 3

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    End point title
    		 Hemoglobin - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [99]
    22
    Units: g/dl
        arithmetic mean (standard deviation)
    13.2 ( 1.8 )
    14.0 ( 1.4 )
    Notes
    [99] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis Hemoglobin - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.685
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hemoglobin - 3 Months

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    End point title
    		 Hemoglobin - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [100]
    22
    Units: g/dl
        arithmetic mean (standard deviation)
    14.2 ( 2.4 )
    14.2 ( 1.7 )
    Notes
    [100] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis Hemoglobin - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.005
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hematocrit - Baseline

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    End point title
    		 Hematocrit - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [101]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    41.0 ( 4.5 )
    42.4 ( 3.4 )
    Notes
    [101] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Hematocrit - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.284
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hematocrit - Day 1

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    End point title
    		 Hematocrit - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [102]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    40.9 ( 4.6 )
    42.1 ( 3.5 )
    Notes
    [102] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    Statistical analysis title
    		 Analysis Hematocrit - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.761
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hematocrit - Day 3

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    End point title
    		 Hematocrit - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    19 [103]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    39.9 ( 4.5 )
    41.5 ( 3.7 )
    Notes
    [103] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
    Statistical analysis title
    		 Analysis Hematocrit - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.93
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Hematocrit - 3 Months

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    End point title
    		 Hematocrit - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [104]
    22
    Units: percentage
        arithmetic mean (standard deviation)
    43.3 ( 5.6 )
    42.3 ( 4.6 )
    Notes
    [104] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis Hematocrit - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Urinary volume - Baseline

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    End point title
    		 Urinary volume - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [105]
    20 [106]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    1740 ( 601 )
    1788 ( 756 )
    Notes
    [105] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [106] - 2 missing data
    Statistical analysis title
    		 Analysis Urinary volume - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.829
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Urinary volume - Day 1

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    End point title
    		 Urinary volume - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [107]
    21 [108]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    2112 ( 837 )
    1626 ( 681 )
    Notes
    [107] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [108] - 1 missing data
    Statistical analysis title
    		 Analysis Urinary volume - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Urinary volume - Day 3

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    End point title
    		 Urinary volume - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [109]
    21 [110]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    2111 ( 758 )
    2007 ( 913 )
    Notes
    [109] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    [110] - 1 missing data
    Statistical analysis title
    		 Analysis Urinary volume - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    39
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.429
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Urinary volume - 3 Months

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    End point title
    		 Urinary volume - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    16 [111]
    21 [112]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    2319 ( 873 )
    1664 ( 594 )
    Notes
    [111] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
    [112] - 1 missing data
    Statistical analysis title
    		 Analysis Urinary volume - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    37
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Electrolyte-free water clearance - Baseline

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    End point title
    		 Electrolyte-free water clearance - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [113]
    20 [114]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    166 ( 830 )
    -15 ( 721 )
    Notes
    [113] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [114] - 2 missing data
    Statistical analysis title
    		 Analysis EF WC - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.467
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Electrolyte-free water clearance - Day 1

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    End point title
    		 Electrolyte-free water clearance - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    20 [115]
    21 [116]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    417 ( 802 )
    -124 ( 654 )
    Notes
    [115] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
    [116] - 1 missing data
    Statistical analysis title
    		 Analysis EF WC - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Electrolyte-free water clearance - Day 3

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    End point title
    		 Electrolyte-free water clearance - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    17 [117]
    21 [118]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    461 ( 551 )
    90 ( 874 )
    Notes
    [117] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
    [118] - 1 missing data
    Statistical analysis title
    		 Analysis EF WC - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    38
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.07
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Electrolyte-free water clearance - 3 Months

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    End point title
    		 Electrolyte-free water clearance - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    16 [119]
    20 [120]
    Units: ml/24hrs
        arithmetic mean (standard deviation)
    380 ( 765 )
    -91 ( 597 )
    Notes
    [119] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
    [120] - 2 missing data
    Statistical analysis title
    		 Analysis EF WC - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    36
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.013
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular enddiastolic diameter - Baseline

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    End point title
    		 Left ventricular enddiastolic diameter - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [121]
    22
    Units: mm
        arithmetic mean (standard deviation)
    49 ( 5 )
    50 ( 5 )
    Notes
    [121] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVEDD - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.365
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular enddiastolic diameter - Day 1

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    End point title
    		 Left ventricular enddiastolic diameter - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [122]
    22
    Units: mm
        arithmetic mean (standard deviation)
    49 ( 5 )
    50 ( 6 )
    Notes
    [122] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVEDD - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.864
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular enddiastolic diameter - Day 3

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    End point title
    		 Left ventricular enddiastolic diameter - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [123]
    22
    Units: mm
        arithmetic mean (standard deviation)
    48 ( 5 )
    49 ( 5 )
    Notes
    [123] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVEDD - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.449
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular enddiastolic diameter - 3 Months

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    End point title
    		 Left ventricular enddiastolic diameter - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [124]
    22
    Units: mm
        arithmetic mean (standard deviation)
    48 ( 6 )
    50 ( 6 )
    Notes
    [124] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVEDD - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.994
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular endsystolic diameter - Baseline

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    End point title
    		 Left ventricular endsystolic diameter - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [125]
    22
    Units: mm
        arithmetic mean (standard deviation)
    34 ( 6 )
    36 ( 8 )
    Notes
    [125] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVESD - Baseline
    Comparison groups
    Placebo v Empagliflozin
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.386
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular endsystolic diameter - Day 1

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    End point title
    		 Left ventricular endsystolic diameter - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [126]
    22
    Units: mm
        arithmetic mean (standard deviation)
    35 ( 5 )
    36 ( 9 )
    Notes
    [126] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVESD - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.595
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular endsystolic diameter - Day 3

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    End point title
    		 Left ventricular endsystolic diameter - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [127]
    22
    Units: mm
        arithmetic mean (standard deviation)
    34 ( 5 )
    35 ( 8 )
    Notes
    [127] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVESD - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.187
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular endsystolic diameter - 3 Months

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    End point title
    		 Left ventricular endsystolic diameter - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [128]
    22
    Units: mm
        arithmetic mean (standard deviation)
    33 ( 6 )
    37 ( 8 )
    Notes
    [128] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LVESD - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.284
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Interventricular septum in diastole - Baseline

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    End point title
    		 Interventricular septum in diastole - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [129]
    22
    Units: mm
        arithmetic mean (standard deviation)
    10 ( 1 )
    10 ( 2 )
    Notes
    [129] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis IVSd - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.94
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Interventricular septum in diastole - Day 1

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    End point title
    		 Interventricular septum in diastole - Day 1
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 1
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [130]
    22
    Units: mm
        arithmetic mean (standard deviation)
    11 ( 2 )
    10 ( 2 )
    Notes
    [130] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis IVSd - Day 1
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.764
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Interventricular septum in diastole - Day 3

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    End point title
    		 Interventricular septum in diastole - Day 3
    End point description
    End point type
    Post-hoc
    End point timeframe
    Day 3
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [131]
    22
    Units: mm
        arithmetic mean (standard deviation)
    11 ( 2 )
    10 ( 2 )
    Notes
    [131] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis IVSd - Day 3
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.63
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Interventricular septum in diastole - 3 Months

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    End point title
    		 Interventricular septum in diastole - 3 Months
    End point description
    End point type
    Post-hoc
    End point timeframe
    3 Months
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [132]
    22
    Units: mm
        arithmetic mean (standard deviation)
    10 ( 1 )
    10 ( 2 )
    Notes
    [132] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis IVSd - 3 Months
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.497
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular mass index - Baseline

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    End point title
    		 Left ventricular mass index - Baseline
    End point description
    End point type
    Post-hoc
    End point timeframe
    Baseline
    End point values
    		 Empagliflozin Placebo
    Number of subjects analysed
    18 [133]
    22
    Units: g/m²
        arithmetic mean (standard deviation)
    86 ( 19 )
    91 ( 21 )
    Notes
    [133] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
    Statistical analysis title
    		 Analysis LV MI - Baseline
    Comparison groups
    Empagliflozin v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.474
    Method
    		 Wald test
    Confidence interval

    Post-hoc: Left ventricular mass index - Day 1