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    Clinical Trial Results:
    Does Dapaglifozin Regress Left Ventricular Hypertrophy In Patients With Type 2 Diabetes?

    Summary
    EudraCT number
    2016-000715-33
    Trial protocol
    GB  
    Global end of trial date
    15 Mar 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    03 Mar 2020
    First version publication date
    03 Mar 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    2015DM07
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    University of Dundee
    Sponsor organisation address
    Ninewells Hospital , Dundee, United Kingdom, DD1 9SY
    Public contact
    Chim , University of Dundee, +44 01382 383013, c.c.lang@dundee.ac.uk
    Scientific contact
    Lang, University of Dundee, +44 01382 383013, c.c.lang@dundee.ac.uk
    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
    31 Jul 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Mar 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Mar 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To see if Dapagliflozin reduces left ventricular mass more than placebo in participants with type 2 diabetes and left ventricular hypertrophy
    Protection of trial subjects
    Not applicable
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Feb 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 66
    Worldwide total number of subjects
    66
    EEA total number of subjects
    66
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    32
    From 65 to 84 years
    34
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Recruitment took place from February 2017 to May 2018

    Pre-assignment
    Screening details
    1541 invitation letters were sent. Overall 473 (31%) replied that they were interested. 153 were excluded from invitation if eligibility criteria were not met. A total of 320 participants were screened from February 2017 to May 2018. Out of the 320 patients screened 254 were excluded and 66 were recruited

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Monitor, Data analyst, Subject
    Blinding implementation details
    Participants were randomised to receive either dapagliflozin (10mg) or placebo in a double blind, randomised fashion. Trial medications were produced and packaged by Astra Zeneca but labelling of the packages were done by Tayside Pharmaceuticals. Randomisation was via TRuST, a GCP compliant web-based system, run by the Tayside Clinical Trials Unit (TCTU), to preserve allocation concealment

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Dapaglilflozin
    Arm description
    Treatment arm which received dapagliflozin
    Arm type
    Active comparator

    Investigational medicinal product name
    Dapagliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10mg Once daily orally for 12 months

    Arm title
    Placebo
    Arm description
    Participants which received placebo
    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 placebo tablet daily orally

    Number of subjects in period 1
    Dapaglilflozin Placebo
    Started
    32
    34
    Completed
    29
    33
    Not completed
    3
    1
         Unable to get holiday insurance
    1
    -
         Adverse event, non-fatal
    1
    1
         Claustrophobia
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    -

    Reporting group values
    Overall Trial Total
    Number of subjects
    66 66
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    32 32
        From 65-84 years
    34 34
        85 years and over
    0 0
    Gender categorical
    Units: Subjects
        Female
    28 28
        Male
    38 38

    End points

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    End points reporting groups
    Reporting group title
    Dapaglilflozin
    Reporting group description
    Treatment arm which received dapagliflozin

    Reporting group title
    Placebo
    Reporting group description
    Participants which received placebo

    Primary: Left ventricular mass change

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    End point title
    Left ventricular mass change
    End point description
    Change in Left ventricular mass measured by Cardiac MRI
    End point type
    Primary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: Grams
        arithmetic mean (standard deviation)
    -3.95 ± 4.85
    -1.13 ± 4.55
    Statistical analysis title
    LVM change difference
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.018 [1]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.13
         upper limit
    -0.51
    Variability estimate
    Standard deviation
    Notes
    [1] - Significant result

    Secondary: Left ventricular mass change indexed to body surface area

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    End point title
    Left ventricular mass change indexed to body surface area
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: g/m2
        arithmetic mean (standard deviation)
    -0.58 ± 2.29
    -0.38 ± 1.79
    Statistical analysis title
    LVM indexed to BSA change difference
    Statistical analysis description
    Independent T -test
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.691 [3]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.21
         upper limit
    0.8
    Variability estimate
    Standard deviation
    Notes
    [2] - Intention to treat
    [3] - Non-Significant difference

    Secondary: Left ventricular ejection fraction change

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    End point title
    Left ventricular ejection fraction change
    End point description
    Change in left ventricular ejection fraction as measured by cardiac MRI
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: Percentage
        arithmetic mean (standard deviation)
    1.45 ± 4.08
    0.66 ± 3.76
    Statistical analysis title
    Left Ventricular ejection fraction change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    = 0.415
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    0.79
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.14
         upper limit
    2.72
    Variability estimate
    Standard deviation
    Notes
    [4] - Intention to treat

    Secondary: End Diastolic Volume

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    End point title
    End Diastolic Volume
    End point description
    Change in EDV as measured by cardiac MRI
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mls
        arithmetic mean (standard deviation)
    -0.15 ± 11.59
    1.44 ± 10.62
    Statistical analysis title
    End Diastolic Volume Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.562 [5]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.06
         upper limit
    3.97
    Variability estimate
    Standard deviation
    Notes
    [5] - Not -signficant

    Secondary: End Systolic Volume

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    End point title
    End Systolic Volume
    End point description
    Change in end systolic volume as measured by cardiac MRI
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mls
        arithmetic mean (standard deviation)
    -1.86 ± 4.83
    -0.74 ± 4.81
    Statistical analysis title
    End Systolic Volume
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.348 [6]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.5
         upper limit
    1.25
    Variability estimate
    Standard deviation
    Notes
    [6] - Not significant

    Secondary: Stoke volume difference

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    End point title
    Stoke volume difference
    End point description
    Change in stroke volume as measured by cardiac MRI
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mls
        arithmetic mean (standard deviation)
    1.71 ± 11.18
    2.18 ± 10.45
    Statistical analysis title
    Stroke volume change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.86 [7]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.79
         upper limit
    4.85
    Variability estimate
    Standard deviation
    Notes
    [7] - Not significant

    Secondary: Cardiac Output

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    End point title
    Cardiac Output
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mls/min
        arithmetic mean (standard deviation)
    244.75 ± 1155.82
    12.91 ± 865.14
    Statistical analysis title
    Cardiac Output change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.307 [8]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -257.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -757.75
         upper limit
    242.43
    Variability estimate
    Standard deviation
    Notes
    [8] - Not -significant

    Secondary: Left atrial volume

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    End point title
    Left atrial volume
    End point description
    Change in left atrial volume as measured by cardiac MRI
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mls
        arithmetic mean (standard deviation)
    -3.09 ± 10.12
    -1.51 ± 8.81
    Statistical analysis title
    Left atrial volume change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.501 [9]
    Method
    t-test, 2-sided
    Parameter type
    Median difference (final values)
    Point estimate
    -1.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.24
         upper limit
    3.08
    Variability estimate
    Standard deviation
    Notes
    [9] - Not-significant

    Secondary: 24 Hour systolic blood pressure

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    End point title
    24 Hour systolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    33
    Units: mmHg
        arithmetic mean (standard deviation)
    -2.78 ± 5.94
    0.85 ± 5.40
    Statistical analysis title
    24 hour blood pressure change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    superiority [10]
    P-value
    = 0.012 [11]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.63
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.44
         upper limit
    -0.82
    Variability estimate
    Standard deviation
    Notes
    [10] - Intention to treat analysis
    [11] - Significant

    Secondary: 24 hour diastolic blood pressure

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    End point title
    24 hour diastolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    33
    Units: mmHg
        arithmetic mean (standard deviation)
    -0.94 ± 3.98
    0.06 ± 4.87
    Statistical analysis title
    24 hour diastolic blood pressure change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    superiority [12]
    P-value
    = 0.37 [13]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.2
         upper limit
    1.21
    Variability estimate
    Standard deviation
    Notes
    [12] - Intention to treat analysis
    [13] - Non-significant

    Secondary: Daytime systolic blood pressure

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    End point title
    Daytime systolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    33
    Units: mmHg
        arithmetic mean (standard deviation)
    -2.47 ± 6.56
    0.55 ± 6.45
    Statistical analysis title
    Daytime systolic blood pressure change
    Statistical analysis description
    Intention to treat
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.066 [14]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.24
         upper limit
    0.21
    Variability estimate
    Standard deviation
    Notes
    [14] - Non-significant

    Secondary: Daytime diastolic blood pressure

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    End point title
    Daytime diastolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    33
    Units: mmHg
        arithmetic mean (standard deviation)
    -1.03 ± 5.18
    0.24 ± 5.80
    Statistical analysis title
    Daytime diastolic blood pressure change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    superiority [15]
    P-value
    = 0.355
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4
         upper limit
    1.46
    Variability estimate
    Standard deviation
    Notes
    [15] - Intention to treat

    Secondary: Nocturnal systolic blood pressure

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    End point title
    Nocturnal systolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    32
    Units: mmHg
        arithmetic mean (standard deviation)
    -3.47 ± 7.54
    0.91 ± 6.70
    Statistical analysis title
    Nocturnal systolic blood pressure change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    superiority [16]
    P-value
    = 0.017 [17]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -4.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.94
         upper limit
    -0.81
    Variability estimate
    Standard deviation
    Notes
    [16] - Intention to treat
    [17] - Significant

    Secondary: Nocturnal diastolic blood pressure

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    End point title
    Nocturnal diastolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    32
    Units: mmHg
        arithmetic mean (standard deviation)
    -2.25 ± 5.90
    0.16 ± 4.14
    Statistical analysis title
    Nocturnal diastolic blood pressure change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    superiority [18]
    P-value
    = 0.063
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.95
         upper limit
    0.14
    Variability estimate
    Standard deviation
    Notes
    [18] - Intention to treat

    Secondary: Office systolic blood pressure

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    End point title
    Office systolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmHg
        arithmetic mean (standard deviation)
    -5.28 ± 8.63
    -1.79 ± 7.26
    Statistical analysis title
    Office systolic blood pressure change
    Statistical analysis description
    Intention to treat analysis
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.08 [19]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.4
         upper limit
    0.43
    Variability estimate
    Standard deviation
    Notes
    [19] - Not significant

    Secondary: Office diastolic blood pressure

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    End point title
    Office diastolic blood pressure
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmHg
        arithmetic mean (standard deviation)
    -2.97 ± 5.62
    -2.24 ± 7.48
    Statistical analysis title
    Office diastolic blood pressure change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [20]
    P-value
    = 0.656 [21]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.73
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4
         upper limit
    2.54
    Variability estimate
    Standard deviation
    Notes
    [20] - Intention to treat analysis
    [21] - Non-significant

    Secondary: Visceral adipose tissue volume

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    End point title
    Visceral adipose tissue volume
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    31
    34
    Units: cm3
        arithmetic mean (standard deviation)
    -565.17 ± 691.27
    114.22 ± 593.69
    Statistical analysis title
    Visceral adipose tissue volume change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    superiority [22]
    P-value
    < 0.001
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -679.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -998
         upper limit
    -360.8
    Variability estimate
    Standard deviation
    Notes
    [22] - Intention to treat analysis

    Secondary: Subcutaneous adipose tissue volume

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    End point title
    Subcutaneous adipose tissue volume
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    31
    31
    Units: cm3
        arithmetic mean (standard deviation)
    -720.84 ± 687.83
    -111.08 ± 643.42
    Statistical analysis title
    Subcutaneous adipose tissue volume change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -609.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -948.13
         upper limit
    -271.28
    Variability estimate
    Standard deviation

    Secondary: Weight

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    End point title
    Weight
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: Kg
        arithmetic mean (standard deviation)
    -4.27 ± 2.50
    -0.50 ± 2.19
    Statistical analysis title
    Weight Change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [23]
    P-value
    < 0.001
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.77
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.92
         upper limit
    -2.61
    Variability estimate
    Standard deviation
    Notes
    [23] - Intention to Treat

    Secondary: BMI

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    End point title
    BMI
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: Kg/m2
        arithmetic mean (standard deviation)
    -1.53 ± 0.93
    -0.17 ± 0.74
    Statistical analysis title
    BMI Change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [24]
    P-value
    < 0.001
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.77
         upper limit
    -0.94
    Variability estimate
    Standard deviation
    Notes
    [24] - Intention to treat analysis

    Secondary: Waist Circumference

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    End point title
    Waist Circumference
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: cm
        arithmetic mean (standard deviation)
    -3.23 ± 2.23
    -1.39 ± 2.18
    Statistical analysis title
    Waist Circumference Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [25]
    P-value
    = 0.001 [26]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.83
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.92
         upper limit
    -0.75
    Variability estimate
    Standard deviation
    Notes
    [25] - Intention to treat analysis
    [26] - Significant

    Secondary: Hip Circumference

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    End point title
    Hip Circumference
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: cm
        arithmetic mean (standard deviation)
    -3.39 ± 2.11
    -1.33 ± 2.21
    Statistical analysis title
    Hip Circumference Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [27]
    P-value
    < 0.001 [28]
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.13
         upper limit
    -1
    Variability estimate
    Standard deviation
    Notes
    [27] - Intention to treat
    [28] - Significant

    Secondary: Deceleration time

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    End point title
    Deceleration time
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: ms
        arithmetic mean (standard deviation)
    -8.47 ± 57.34
    4.18 ± 44.90
    Statistical analysis title
    Deceleration time change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [29]
    P-value
    = 0.321
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -12.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -37.89
         upper limit
    12.6
    Variability estimate
    Standard deviation
    Notes
    [29] - Intention to treat analysis

    Secondary: Early lateral annular tissue doppler velocity

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    End point title
    Early lateral annular tissue doppler velocity
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: cm/s
        arithmetic mean (standard deviation)
    0.74 ± 2.37
    0.49 ± 1.80
    Statistical analysis title
    Early lateral annular tissue doppler velocity
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [30]
    P-value
    = 0.635
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.78
         upper limit
    1.28
    Variability estimate
    Standard deviation
    Notes
    [30] - Intention to treat analysis

    Secondary: Early septal annular tissue doppler velocity

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    End point title
    Early septal annular tissue doppler velocity
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: cm/s
        arithmetic mean (standard deviation)
    0.56 ± 2.22
    0.26 ± 1.36
    Statistical analysis title
    Early septall annular tissue doppler velocity
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.503
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    1.2
    Variability estimate
    Standard deviation

    Secondary: Global longitudinal strain

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    End point title
    Global longitudinal strain
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    24
    25
    Units: percentage
        arithmetic mean (standard deviation)
    -1.64 ± 2.51
    -0.21 ± 1.75
    Statistical analysis title
    Global longitudinal strain
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    superiority [31]
    P-value
    = 0.024
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.67
         upper limit
    -0.19
    Variability estimate
    Standard deviation
    Notes
    [31] - Intention to treat analysis

    Secondary: E/A Ratio

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    End point title
    E/A Ratio
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: ratio
        median (inter-quartile range (Q1-Q3))
    0.00 (-0.20 to 0.20)
    0.00 (-0.20 to 0.20)
    Statistical analysis title
    E/A Ratio change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [32]
    P-value
    = 0.587
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    0.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    0.14
    Variability estimate
    Standard deviation
    Notes
    [32] - Intention to treat analysis

    Secondary: E to e ratio

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    End point title
    E to e ratio
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: ratio
        median (inter-quartile range (Q1-Q3))
    0.00 (-2.00 to 2.00)
    0.10 (-0.4 to 0.20)
    Statistical analysis title
    E/e ratio change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [33]
    P-value
    = 0.621
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    1.1
    Variability estimate
    Standard deviation
    Notes
    [33] - Intention to treat analysis

    Secondary: Haemoglobin

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    End point title
    Haemoglobin
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: g/l
        arithmetic mean (standard deviation)
    7.00 ± 11.75
    -2.00 ± 5.00
    Statistical analysis title
    Haemoglobin change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [34]
    P-value
    < 0.001
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    9.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.85
         upper limit
    13.18
    Variability estimate
    Standard deviation
    Notes
    [34] - Intention to treat

    Secondary: Haematocrit

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    End point title
    Haematocrit
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: Percentage
        arithmetic mean (standard deviation)
    2.60 ± 0.02
    0.30 ± 0.02
    Statistical analysis title
    Haematocrit change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [35]
    P-value
    < 0.001
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    2.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.84
         upper limit
    3.96
    Variability estimate
    Standard deviation
    Notes
    [35] - Intention to treat analysis

    Secondary: Creatinine

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    End point title
    Creatinine
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: umol/L
        arithmetic mean (standard deviation)
    1.34 ± 5.89
    -0.91 ± 5.83
    Statistical analysis title
    Creatinine Change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [36]
    P-value
    = 0.123
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    2.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.63
         upper limit
    5.14
    Variability estimate
    Standard deviation
    Notes
    [36] - Intention to treat analysis

    Secondary: Estimated GFR

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    End point title
    Estimated GFR
    End point description
    End point type
    Secondary
    End point timeframe
    12 Months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: ml/min/1.732
        arithmetic mean (standard deviation)
    -1.16 ± 10.48
    1.59 ± 7.19
    Statistical analysis title
    Estimated GFR Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [37]
    P-value
    = 0.217
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (net)
    Point estimate
    -2.74
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.14
         upper limit
    1.65
    Variability estimate
    Standard deviation
    Notes
    [37] - Intention to treat analysis

    Secondary: Fasting Glucose

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    End point title
    Fasting Glucose
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmol/L
        arithmetic mean (standard deviation)
    -1.06 ± 2.08
    0.62 ± 2.11
    Statistical analysis title
    Fasting Glucose Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.68
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.71
         upper limit
    -0.65
    Variability estimate
    Standard deviation

    Secondary: HbA1c

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    End point title
    HbA1c
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmol/mol
        arithmetic mean (standard deviation)
    -6.28 ± 8.25
    -0.79 ± 10.89
    Statistical analysis title
    HbA1c
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [38]
    P-value
    = 0.025
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -5.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.26
         upper limit
    -0.71
    Variability estimate
    Standard deviation
    Notes
    [38] - Intention to treat analysis

    Secondary: LDL Cholesterol

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    End point title
    LDL Cholesterol
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmol/mol
        arithmetic mean (standard deviation)
    -0.14 ± 0.31
    -0.08 ± 0.45
    Statistical analysis title
    LDL Cholesterol change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.522
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    0.13
    Variability estimate
    Standard deviation

    Secondary: Total cholesterol

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    End point title
    Total cholesterol
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmol/mol
        median (inter-quartile range (Q1-Q3))
    -0.10 (-0.30 to 0.03)
    -0.17 (-0.38 to 0.11)
    Statistical analysis title
    Total cholesterol
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [39]
    P-value
    = 0.995
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (net)
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.28
         upper limit
    0.15
    Variability estimate
    Standard deviation
    Notes
    [39] - Intention to treat analysis

    Secondary: HDL Cholesterol

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    End point title
    HDL Cholesterol
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmol/l
        median (inter-quartile range (Q1-Q3))
    0.06 (-0.02 to 0.17)
    0.00 (-0.04 to 0.06)
    Statistical analysis title
    HDL Cholesterol
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [40]
    P-value
    = 0.031
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    0.15
    Variability estimate
    Standard deviation
    Notes
    [40] - Intention to treat analysis

    Secondary: Total Cholesterol to HDL ratio

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    End point title
    Total Cholesterol to HDL ratio
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: Ratio
        median (inter-quartile range (Q1-Q3))
    -0.20 (-0.50 to -0.03)
    -0.10 (-0.30 to 0.13)
    Statistical analysis title
    Total cholesterol to HDL ratio change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [41]
    P-value
    = 0.085
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.43
         upper limit
    0.01
    Variability estimate
    Standard deviation
    Notes
    [41] - Intention to treat analysis

    Secondary: Triglycerides

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    End point title
    Triglycerides
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: mmol/l
        median (inter-quartile range (Q1-Q3))
    -0.11 (-0.31 to 0.00)
    0.01 (-0.26 to 0.35)
    Statistical analysis title
    Triglycerides Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [42]
    P-value
    = 0.064
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.41
         upper limit
    0.08
    Variability estimate
    Standard deviation
    Notes
    [42] - Intention to Treat analysis

    Secondary: NTproBNP

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    End point title
    NTproBNP
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: pg/ml
        median (inter-quartile range (Q1-Q3))
    7.14 (-41.25 to 97.44)
    40.19 (-68.69 to 150.78)
    Statistical analysis title
    NTproBNP change
    Comparison groups
    Placebo v Dapaglilflozin
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [43]
    P-value
    = 0.551
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -103.68
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -326.9
         upper limit
    119.54
    Variability estimate
    Standard deviation
    Notes
    [43] - Intention to treat analysis

    Secondary: Leptin

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    End point title
    Leptin
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: pg/ml
        median (inter-quartile range (Q1-Q3))
    -447.55 (-4122.50 to 1170.00)
    477.60 (-3200.00 to 3120.00)
    Statistical analysis title
    Leptin Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [44]
    P-value
    = 0.256
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -2931.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6901.46
         upper limit
    1038.07
    Variability estimate
    Standard deviation
    Notes
    [44] - Intention to treat analysis

    Secondary: Myeloperoxidase

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    End point title
    Myeloperoxidase
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: ng/ml
        median (inter-quartile range (Q1-Q3))
    0.00 (-73.56 to 33.48)
    -36.49 (-36.49 to 7.28)
    Statistical analysis title
    Myeloperoxidase Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.172
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    23.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -31.05
         upper limit
    77.08
    Variability estimate
    Standard deviation

    Secondary: NT pro collagen

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    End point title
    NT pro collagen
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: ng/ml
        arithmetic mean (standard deviation)
    -0.44 ± 5.06
    -0.10 ± 4.24
    Statistical analysis title
    NT pro collagen change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [45]
    P-value
    = 0.653
    Method
    t-test, 2-sided
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    1.29
    Variability estimate
    Standard deviation
    Notes
    [45] - Intention to treat analysis

    Secondary: hsCRP

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    End point title
    hsCRP
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    32
    34
    Units: ng/l
        median (inter-quartile range (Q1-Q3))
    -163.73 (-991.86 to 48.90)
    66.73 (-469.26 to 789.10)
    Statistical analysis title
    hs CRP Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    superiority [46]
    P-value
    = 0.049
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -1296.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2650.59
         upper limit
    -31.5
    Variability estimate
    Standard deviation
    Notes
    [46] - Intention to treat analysis

    Secondary: Fasting Insulin

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    End point title
    Fasting Insulin
    End point description
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    22
    26
    Units: uU/ml
        median (inter-quartile range (Q1-Q3))
    -2.34 (-5.46 to 0.13)
    -0.58 (-3.43 to 3.71)
    Statistical analysis title
    Fasting Insulin Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.098
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.97
         upper limit
    -0.26
    Variability estimate
    Standard deviation

    Secondary: HOMA-IR

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    End point title
    HOMA-IR
    End point description
    End point type
    Secondary
    End point timeframe
    12 Months
    End point values
    Dapaglilflozin Placebo
    Number of subjects analysed
    22
    26
    Units: BLANK
        median (inter-quartile range (Q1-Q3))
    -1.29 (-2.34 to 0.02)
    -0.22 (-1.27 to 1.96)
    Statistical analysis title
    HOMA-IR Change
    Comparison groups
    Dapaglilflozin v Placebo
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    superiority [47]
    P-value
    = 0.017
    Method
    Wilcoxon (Mann-Whitney)
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.47
         upper limit
    -0.65
    Variability estimate
    Standard deviation
    Notes
    [47] - Intention to treat analysis

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from February 2017 to May 2019
    Adverse event reporting additional description
    Adverse events were assessed at every trial visit. Participants were also encouraged to contact myself the Principal investigator for the trial if adverse events developed. All reported adverse events (AEs) were recorded in detail on an adverse event CRF page.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Adverse Events Dapagliflozin
    Reporting group description
    Adverse events affecting the dapaglilfozin arm

    Reporting group title
    Adverse Events Placebo
    Reporting group description
    Adverse events reported in the placebo arm

    Serious adverse events
    Adverse Events Dapagliflozin Adverse Events Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 32 (3.13%)
    3 / 34 (8.82%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Jaw Fracture
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer female
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Haematemesis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    Adverse Events Dapagliflozin Adverse Events Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    24 / 32 (75.00%)
    30 / 34 (88.24%)
    Vascular disorders
    Postural Hypotension
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Night sweats
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Anorexia
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Joint injury
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Fall
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Elevated Liver Enzymes
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Cardiac disorders
    Chest Pain
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 32 (9.38%)
    2 / 34 (5.88%)
         occurrences all number
    3
    2
    Cold
         subjects affected / exposed
    4 / 32 (12.50%)
    5 / 34 (14.71%)
         occurrences all number
    4
    5
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 32 (3.13%)
    4 / 34 (11.76%)
         occurrences all number
    1
    4
    Flu
         subjects affected / exposed
    3 / 32 (9.38%)
    3 / 34 (8.82%)
         occurrences all number
    3
    3
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Sciatica
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    2
    Vertigo
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Earache
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    0 / 32 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    Diarrhoea
         subjects affected / exposed
    1 / 32 (3.13%)
    2 / 34 (5.88%)
         occurrences all number
    1
    2
    Stomach Pain
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    3 / 32 (9.38%)
    1 / 34 (2.94%)
         occurrences all number
    4
    2
    Indigestion
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Tooth Abscess
         subjects affected / exposed
    1 / 32 (3.13%)
    1 / 34 (2.94%)
         occurrences all number
    1
    1
    Abdominal hernia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Halitosis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Polyuria
         subjects affected / exposed
    8 / 32 (25.00%)
    7 / 34 (20.59%)
         occurrences all number
    8
    7
    Renal failure
    Additional description: Drop in GFR temporary in all cases
         subjects affected / exposed
    2 / 32 (6.25%)
    1 / 34 (2.94%)
         occurrences all number
    2
    1
    Urinary Frequency
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Cellulitis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 32 (6.25%)
    3 / 34 (8.82%)
         occurrences all number
    2
    3
    Supraspinatus Tendonitis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Fracture
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Trigger finger
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Neck Pain
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Knee Pain
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Cramps
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Achilles Tendonitis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Muscle Aches
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    7 / 32 (21.88%)
    3 / 34 (8.82%)
         occurrences all number
    22
    7
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 32 (3.13%)
    2 / 34 (5.88%)
         occurrences all number
    1
    2
    Thirst
         subjects affected / exposed
    1 / 32 (3.13%)
    3 / 34 (8.82%)
         occurrences all number
    1
    3
    Hyponatraemia
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 32 (3.13%)
    4 / 34 (11.76%)
         occurrences all number
    1
    6
    Tinea Pedis
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    Thrush
         subjects affected / exposed
    12 / 32 (37.50%)
    2 / 34 (5.88%)
         occurrences all number
    12
    2
    Ear infection
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Nov 2016
    AM01 Response to MHRA following initial submission Exclusion criteria updated to say that patients with electrolyte disturbance would be excluded. Patients with a history of DKA to be excluded. Asked to clarify women of child bearing potential therefore added to protocol that they would be defined as premenopausal women who have not been surgically sterilised or had a hysterectomy, bilateral salpingoophorectomy or bilateral oophorectomy. Women over 45 years old, who had no had a menstrual period for at least 12 months without an alternative cause were considered as post menopausal Added that women of child bearing age would have a urine pregnancy test pre starting the study and this would be repeated and documented every 4 weeks throughout their participation in the trial Asked to add that if a participant was commenced on loop diuretics would be discontinued from the trial
    02 Jun 2017
    AMO2 Changed lower limit of HbA1c cut off for inclusion from 53mmol/mol to 48mmol/mol Changed echocardiographic inclusion criteria to include LVH indexed to Height2.7 in addition to BSA Changed age cut off for inclusion from 75 to 80 years of age Increased weight cut off in inclusion criteria to 150kg from 120kg Added the use of the Scottish primary care research network to recruit participants Extended recruitment to Fife Added that participants would undergo an echocardiogram at the end of the study to allow the comparison of diastolic parameters and longitudinal analysis with baseline echocardiogram Allowed the ability to repeat Sodium and Potassium blood tests if tests at a review visit were abnormal to avoid unnecessary withdrawal.
    12 Dec 2017
    AMO3 Change of CI from Prof Allan Struthers to Prof Chim Lang due to Prof Struthers retiring Made a change to allow any patients who dropped out whilst recruitment was still underway to be replaced Change the GFR cut off in inclusion criteria from <60 TO < 45ml/min Following discussion with the MHRA clarified that adverse reactions with Dapagliflozin did not need to be reported via the yellow card scheme
    03 Sep 2018
    Non substantial amendment AMO4 Reduced follow up from 12months to a minimum of 10 months In the previous amendment we were allowed to replace any withdrawals during the recruitment period. Protocol therefore changed from 64 participants to 66 as 66 had been recruited at the completion of recruitment
    31 Jan 2019
    AM05 Non substantial amendment Due to funding we elected to only analyse biomarkers at the beginning and end of the study Post reading the up to date literature we decided to analyse - Myeloperoxidase, Leptin, hsCRP, NT pro BNP, procollagenIII. This was therefore added to the protocol

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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