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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 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

Trial information Top of page

Subject disposition Top of page
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	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 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 -

Subject disposition Top of page

Baseline characteristics Top of page
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 -

Baseline characteristics Top of page

End points Top of page
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.

End points Top of page

Primary: Systemic vascular resistance index - Baseline Top of page
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 - Baseline Top of page

Primary: Systemic vascular resistance index - Day 1 Top of page
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 1 Top of page

Primary: Systemic vascular resistance index - Day 3 Top of page
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 - Day 3 Top of page

Primary: Systemic vascular resistance index - 3 Months Top of page
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: Systemic vascular resistance index - 3 Months Top of page

Primary: Cardiac index - Baseline Top of page
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 - Baseline Top of page

Primary: Cardiac index - Day 1 Top of page
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 1 Top of page

Primary: Cardiac index - Day 3 Top of page
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 - Day 3 Top of page

Primary: Cardiac index - 3 Months Top of page
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

Primary: Cardiac index - 3 Months Top of page

Secondary: Heart rate - Baseline Top of page
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 - Baseline Top of page

Secondary: Heart rate - Day 1 Top of page
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 1 Top of page

Secondary: Heart rate - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Heart rate - 3 Months Top of page
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: Heart rate - 3 Months Top of page

Secondary: Systolic blood pressure - Baseline Top of page
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 - Baseline Top of page

Secondary: Systolic blood pressure - Day 1 Top of page
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 1 Top of page

Secondary: Systolic blood pressure - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Systolic blood pressure - 3 Months Top of page
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: Systolic blood pressure - 3 Months Top of page

Secondary: Diastolic blood pressure - Baseline Top of page
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 - Baseline Top of page

Secondary: Diastolic blood pressure - Day 1 Top of page
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 1 Top of page

Secondary: Diastolic blood pressure - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Diastolic blood pressure - 3 Months Top of page
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: Diastolic blood pressure - 3 Months Top of page

Secondary: Stroke volume index - Baseline Top of page
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 - Baseline Top of page

Secondary: Stroke volume index - Day 1 Top of page
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 1 Top of page

Secondary: Stroke volume index - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Stroke volume index - 3 Months Top of page
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: Stroke volume index - 3 Months Top of page

Secondary: Left ventricular ejection fraction - Baseline Top of page
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 - Baseline Top of page

Secondary: Left ventricular ejection fraction - Day 1 Top of page
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 1 Top of page

Secondary: Left ventricular ejection fraction - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Left ventricular ejection fraction - 3 Months Top of page
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 ejection fraction - 3 Months Top of page

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

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

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

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

Secondary: Left atrial volume index - Baseline Top of page
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 - Baseline Top of page

Secondary: Left atrial volume index - Day 1 Top of page
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 1 Top of page

Secondary: Left atrial volume index - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Left atrial volume index - 3 Months Top of page
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: Left atrial volume index - 3 Months Top of page

Secondary: Mitral E-wave velocity - Baseline Top of page
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 - Baseline Top of page

Secondary: Mitral E-wave velocity - Day 1 Top of page
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 1 Top of page

Secondary: Mitral E-wave velocity - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Mitral E-wave velocity - 3 Months Top of page
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: Mitral E-wave velocity - 3 Months Top of page

Secondary: Glucose serum level - Baseline Top of page
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 - Baseline Top of page

Secondary: Glucose serum level - Day 1 Top of page
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 1 Top of page

Secondary: Glucose serum level - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Glucose serum level - 3 Months Top of page
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: Glucose serum level - 3 Months Top of page

Secondary: HbA1c serum level - Baseline Top of page
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 level - Baseline Top of page

Secondary: HbA1c serum leven - Day 1 Top of page
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 leven - Day 1 Top of page

Secondary: HbA1c serum level - Day 3 Top of page
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 - Day 3 Top of page

Secondary: HbA1c serum level - 3 Months Top of page
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: HbA1c serum level - 3 Months Top of page

Secondary: Cystatin C serum level - Baseline Top of page
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 - Baseline Top of page

Secondary: Cystatin C serum level - Day 1 Top of page
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 1 Top of page

Secondary: Cystatin C serum level - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Cystatin C serum level - 3 Months Top of page
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: Cystatin C serum level - 3 Months Top of page

Secondary: NT-proBNP serum level - Baseline Top of page
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 - Baseline Top of page

Secondary: NT-proBNP serum level - Day 1 Top of page
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 1 Top of page

Secondary: NT-proBNP serum level - Day 3 Top of page
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 - Day 3 Top of page

Secondary: NT-proBNP serum level - 3 Months Top of page
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: NT-proBNP serum level - 3 Months Top of page

Secondary: Aldosterone serum level - Baseline Top of page
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 - Baseline Top of page

Secondary: Aldosterone serum level - Day 1 Top of page
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 1 Top of page

Secondary: Aldosterone serum level - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Aldosterone serum level - 3 Months Top of page
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: Aldosterone serum level - 3 Months Top of page

Secondary: Sodium urine excretion - Baseline Top of page
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 - Baseline Top of page

Secondary: Sodium urine excretion - Day 1 Top of page
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 1 Top of page

Secondary: Sodium urine excretion - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Sodium urine excretion - 3 Months Top of page
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: Sodium urine excretion - 3 Months Top of page

Secondary: Glucose urine excretion - Baseline Top of page
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 - Baseline Top of page

Secondary: Glucose urine excretion - Day 1 Top of page
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 1 Top of page

Secondary: Glucose urine excretion - Day 3 Top of page
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 - Day 3 Top of page

Secondary: Glucose urine excretion - 3 Months Top of page
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

Secondary: Glucose urine excretion - 3 Months Top of page

Post-hoc: Total cholesterol serum level - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Total cholesterol serum level - Day 1 Top of page
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 1 Top of page

Post-hoc: Total cholesterol serum level - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Total cholesterol serum level - 3 Months Top of page
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: Total cholesterol serum level - 3 Months Top of page

Post-hoc: LDL-C serum level - Baseline Top of page
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 - Baseline Top of page

Post-hoc: LDL-C serum level - Day 1 Top of page
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 1 Top of page

Post-hoc: LDL-C serum level - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: LDL-C serum level - 3 Months Top of page
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: LDL-C serum level - 3 Months Top of page

Post-hoc: HDL-C serum level - Baseline Top of page
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 - Baseline Top of page

Post-hoc: HDL-C serum level - Day 1 Top of page
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 1 Top of page

Post-hoc: HDL-C serum level - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: HDL-C serum level - 3 Months Top of page
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: HDL-C serum level - 3 Months Top of page

Post-hoc: eGFR - Baseline Top of page
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 - Baseline Top of page

Post-hoc: eGFR - Day 1 Top of page
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 1 Top of page

Post-hoc: eGFR - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: eGFR - 3 Months Top of page
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: eGFR - 3 Months Top of page

Post-hoc: Hemoglobin - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Hemoglobin - Day 1 Top of page
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 1 Top of page

Post-hoc: Hemoglobin - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Hemoglobin - 3 Months Top of page
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: Hemoglobin - 3 Months Top of page

Post-hoc: Hematocrit - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Hematocrit - Day 1 Top of page
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 1 Top of page

Post-hoc: Hematocrit - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Hematocrit - 3 Months Top of page
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: Hematocrit - 3 Months Top of page

Post-hoc: Urinary volume - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Urinary volume - Day 1 Top of page
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 1 Top of page

Post-hoc: Urinary volume - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Urinary volume - 3 Months Top of page
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: Urinary volume - 3 Months Top of page

Post-hoc: Electrolyte-free water clearance - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Electrolyte-free water clearance - Day 1 Top of page
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 1 Top of page

Post-hoc: Electrolyte-free water clearance - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Electrolyte-free water clearance - 3 Months Top of page
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: Electrolyte-free water clearance - 3 Months Top of page

Post-hoc: Left ventricular enddiastolic diameter - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Left ventricular enddiastolic diameter - Day 1 Top of page
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 1 Top of page

Post-hoc: Left ventricular enddiastolic diameter - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Left ventricular enddiastolic diameter - 3 Months Top of page
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 enddiastolic diameter - 3 Months Top of page

Post-hoc: Left ventricular endsystolic diameter - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Left ventricular endsystolic diameter - Day 1 Top of page
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 1 Top of page

Post-hoc: Left ventricular endsystolic diameter - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Left ventricular endsystolic diameter - 3 Months Top of page
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: Left ventricular endsystolic diameter - 3 Months Top of page

Post-hoc: Interventricular septum in diastole - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Interventricular septum in diastole - Day 1 Top of page
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 1 Top of page

Post-hoc: Interventricular septum in diastole - Day 3 Top of page
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 - Day 3 Top of page

Post-hoc: Interventricular septum in diastole - 3 Months Top of page
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: Interventricular septum in diastole - 3 Months Top of page

Post-hoc: Left ventricular mass index - Baseline Top of page
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 - Baseline Top of page

Post-hoc: Left ventricular mass index - Day 1 Top of page
End point title	Left ventricular mass index - 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 [134] 22 Units: g/m²     arithmetic mean (standard deviation) 87 ± 19 94 ± 24
Notes [134] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis LV MI - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.448
Method	Wald test
Confidence interval

Post-hoc: Left ventricular mass index - Day 1 Top of page

Post-hoc: Left ventricular mass index - Day 3 Top of page
End point title	Left ventricular mass index - 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 [135] 22 Units: g/m²     arithmetic mean (standard deviation) 84 ± 19 90 ± 21
Notes [135] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis LV MI - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.701
Method	Wald test
Confidence interval

Post-hoc: Left ventricular mass index - Day 3 Top of page

Post-hoc: Left ventricular mass index - 3 Months Top of page
End point title	Left ventricular mass index - 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 [136] 22 Units: g/m²     arithmetic mean (standard deviation) 84 ± 17 89 ± 23
Notes [136] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis LV MI - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.807
Method	Wald test
Confidence interval

Post-hoc: Left ventricular mass index - 3 Months Top of page

Post-hoc: Left atrial area - Baseline Top of page
End point title	Left atrial area - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 18 [137] 22 Units: cm²     arithmetic mean (standard deviation) 20 ± 3.7 20 ± 4.2
Notes [137] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis LA area - Baseline
Comparison groups	Placebo v Empagliflozin
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.484
Method	Wald test
Confidence interval

Post-hoc: Left atrial area - Baseline Top of page

Post-hoc: Left atrial area - Day 1 Top of page
End point title	Left atrial area - 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 [138] 22 Units: cm²     arithmetic mean (standard deviation) 18 ± 4.3 20 ± 5.3
Notes [138] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis LA area - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.082
Method	Wald test
Confidence interval

Post-hoc: Left atrial area - Day 1 Top of page

Post-hoc: Left atrial area - Day 3 Top of page
End point title	Left atrial area - 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 [139] 22 Units: cm²     arithmetic mean (standard deviation) 19 ± 4.8 20 ± 5.7
Notes [139] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis LA area - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.691
Method	Wald test
Confidence interval

Post-hoc: Left atrial area - Day 3 Top of page

Post-hoc: Left atrial area - 3 Months Top of page
End point title	Left atrial area - 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 [140] 22 Units: cm²     arithmetic mean (standard deviation) 18 ± 4.0 20 ± 4.1
Notes [140] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis LA area - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.503
Method	Wald test
Confidence interval

Post-hoc: Left atrial area - 3 Months Top of page

Post-hoc: Mitral A-wave velocity - Baseline Top of page
End point title	Mitral A-wave velocity - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 17 [141] 21 [142] Units: m/sec     arithmetic mean (standard deviation) 0.82 ± 0.17 0.73 ± 0.17
Notes [141] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data [142] - 1 missing data
Statistical analysis title	Analysis A - Baseline
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	38
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.095
Method	Wald test
Confidence interval

Post-hoc: Mitral A-wave velocity - Baseline Top of page

Post-hoc: Mitral A-wave velocity - Day 1 Top of page
End point title	Mitral A-wave velocity - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 16 [143] 21 [144] Units: m/sec     arithmetic mean (standard deviation) 0.81 ± 0.15 0.74 ± 0.20
Notes [143] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data [144] - 1 missing data
Statistical analysis title	Analysis A - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.786
Method	Wald test
Confidence interval

Post-hoc: Mitral A-wave velocity - Day 1 Top of page

Post-hoc: Mitral A-wave velocity - Day 3 Top of page
End point title	Mitral A-wave velocity - Day 3
End point description
End point type	Post-hoc
End point timeframe	Day 3
End point values Empagliflozin Placebo Number of subjects analysed 15 [145] 22 Units: m/sec     arithmetic mean (standard deviation) 0.80 ± 0.15 0.75 ± 0.19
Notes [145] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 5 missing data
Statistical analysis title	Analysis A - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.55
Method	Wald test
Confidence interval

Post-hoc: Mitral A-wave velocity - Day 3 Top of page

Post-hoc: Mitral A-wave velocity - 3 Months Top of page
End point title	Mitral A-wave velocity - 3 Months
End point description
End point type	Post-hoc
End point timeframe	3 Months
End point values Empagliflozin Placebo Number of subjects analysed 14 [146] 22 Units: m/sec     arithmetic mean (standard deviation) 0.83 ± 0.15 0.73 ± 0.20
Notes [146] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 6 missing data
Statistical analysis title	Analysis A - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	36
Analysis specification	Post-hoc
Analysis type	other
P-value	= 0.927
Method	Wald test
Confidence interval

Post-hoc: Mitral A-wave velocity - 3 Months Top of page

Post-hoc: E/A ratio - Baseline Top of page
End point title	E/A ratio - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 17 [147] 21 [148] Units: none     arithmetic mean (standard deviation) 0.97 ± 0.22 1.18 ± 0.53
Notes [147] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data [148] - 1 missing data
Statistical analysis title	Analysis E/A - Baseline
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	38
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.121
Method	Wald test
Confidence interval

Post-hoc: E/A ratio - Baseline Top of page

Post-hoc: E/A ratio - Day 1 Top of page
End point title	E/A ratio - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 16 [149] 21 [150] Units: none     arithmetic mean (standard deviation) 0.88 ± 0.20 1.20 ± 0.55
Notes [149] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data [150] - 1 missing data
Statistical analysis title	Analysis E/A - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.042
Method	Wald test
Confidence interval

Post-hoc: E/A ratio - Day 1 Top of page

Post-hoc: E/A ratio - Day 3 Top of page
End point title	E/A ratio - Day 3
End point description
End point type	Post-hoc
End point timeframe	Day 3
End point values Empagliflozin Placebo Number of subjects analysed 15 [151] 22 Units: none     arithmetic mean (standard deviation) 0.89 ± 0.23 1.16 ± 0.58
Notes [151] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 5 missing data
Statistical analysis title	Analysis E/A - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.181
Method	Wald test
Confidence interval

Post-hoc: E/A ratio - Day 3 Top of page

Post-hoc: E/A ratio - 3 Months Top of page
End point title	E/A ratio - 3 Months
End point description
End point type	Post-hoc
End point timeframe	3 Months
End point values Empagliflozin Placebo Number of subjects analysed 14 [152] 22 Units: none     arithmetic mean (standard deviation) 0.85 ± 0.23 1.21 ± 0.52
Notes [152] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 6 missing data
Statistical analysis title	Analysis E/A - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	36
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.038
Method	Wald test
Confidence interval

Post-hoc: E/A ratio - 3 Months Top of page

Post-hoc: Mitral annular velocity e' septal - Baseline Top of page
End point title	Mitral annular velocity e' septal - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 20 [153] 22 Units: cm/sec     arithmetic mean (standard deviation) 7.5 ± 1.9 7.2 ± 1.7
Notes [153] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
Statistical analysis title	Analysis e' septal - Baseline
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	42
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.603
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' septal - Baseline Top of page

Post-hoc: Mitral annular velocity e' septal - Day 1 Top of page
End point title	Mitral annular velocity e' septal - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 19 [154] 22 Units: cm/sec     arithmetic mean (standard deviation) 7.8 ± 2.1 6.6 ± 2.0
Notes [154] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
Statistical analysis title	Analysis e' septal - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	41
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.077
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' septal - Day 1 Top of page

Post-hoc: Mitral annular velocity e' septal - Day 3 Top of page
End point title	Mitral annular velocity e' septal - 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 [155] 22 Units: cm/sec     arithmetic mean (standard deviation) 7.5 ± 2.0 7.2 ± 1.6
Notes [155] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
Statistical analysis title	Analysis e' septal - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	41
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.785
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' septal - Day 3 Top of page

Post-hoc: Mitral annular velocity e' septal - 3 Months Top of page
End point title	Mitral annular velocity e' septal - 3 Months
End point description
End point type	Post-hoc
End point timeframe	3 Months
End point values Empagliflozin Placebo Number of subjects analysed 17 [156] 22 Units: cm/sec     arithmetic mean (standard deviation) 7.8 ± 2.1 7.2 ± 1.6
Notes [156] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
Statistical analysis title	Analysis e' septal - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	39
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.47
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' septal - 3 Months Top of page

Post-hoc: Mitral annular velocity e' lateral - Baseline Top of page
End point title	Mitral annular velocity e' lateral - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 20 [157] 22 Units: cm/sec     arithmetic mean (standard deviation) 10.4 ± 1.8 9.8 ± 2.0
Notes [157] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
Statistical analysis title	Analysis e' lateral - Baseline
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	42
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.319
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' lateral - Baseline Top of page

Post-hoc: Mitral annular velocity e' lateral - Day 1 Top of page
End point title	Mitral annular velocity e' lateral - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 19 [158] 22 Units: cm/sec     arithmetic mean (standard deviation) 10.1 ± 2.4 9.6 ± 2.4
Notes [158] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
Statistical analysis title	Analysis e' lateral - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	41
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.97
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' lateral - Day 1 Top of page

Post-hoc: Mitral annular velocity e' lateral - Day 3 Top of page
End point title	Mitral annular velocity e' lateral - 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 [159] 22 Units: cm/sec     arithmetic mean (standard deviation) 9.8 ± 2.3 9.5 ± 1.9
Notes [159] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
Statistical analysis title	Analysis e' lateral - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	41
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.84
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' lateral - Day 3 Top of page

Post-hoc: Mitral annular velocity e' lateral - 3 Months Top of page
End point title	Mitral annular velocity e' lateral - 3 Months
End point description
End point type	Post-hoc
End point timeframe	3 Months
End point values Empagliflozin Placebo Number of subjects analysed 17 [160] 22 Units: cm/sec     arithmetic mean (standard deviation) 10.4 ± 2.9 9.3 ± 2.0
Notes [160] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
Statistical analysis title	Analysis e' lateral - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	39
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.262
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' lateral - 3 Months Top of page

Post-hoc: Mitral annular velocity e' mean - Baseline Top of page
End point title	Mitral annular velocity e' mean - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 20 [161] 22 Units: cm/sec     arithmetic mean (standard deviation) 8.9 ± 1.6 8.5 ± 1.5
Notes [161] - 2 subjects were retrospectively excluded from analysis due to protocol deviations
Statistical analysis title	Analysis e' mean - Baseline
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	42
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.361
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' mean - Baseline Top of page

Post-hoc: Mitral annular velocity e' mean - Day 1 Top of page
End point title	Mitral annular velocity e' mean - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 19 [162] 22 Units: cm/sec     arithmetic mean (standard deviation) 8.9 ± 2.1 8.1 ± 1.8
Notes [162] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
Statistical analysis title	Analysis e' mean - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	41
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.352
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' mean - Day 1 Top of page

Post-hoc: Mitral annular velocity e' mean - Day 3 Top of page
End point title	Mitral annular velocity e' mean - 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 [163] 22 Units: cm/sec     arithmetic mean (standard deviation) 8.7 ± 2.0 8.4 ± 1.3
Notes [163] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 1 missing data
Statistical analysis title	Analysis e' mean - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	41
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.968
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' mean - Day 3 Top of page

Post-hoc: Mitral annular velocity e' mean - 3 Months Top of page
End point title	Mitral annular velocity e' mean - 3 Months
End point description
End point type	Post-hoc
End point timeframe	3 Months
End point values Empagliflozin Placebo Number of subjects analysed 17 [164] 22 Units: cm/sec     arithmetic mean (standard deviation) 9.1 ± 2.3 8.3 ± 1.5
Notes [164] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 3 missing data
Statistical analysis title	Analysis e' mean - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	39
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.28
Method	Wald test
Confidence interval

Post-hoc: Mitral annular velocity e' mean - 3 Months Top of page

Post-hoc: Deceleration time - Baseline Top of page
End point title	Deceleration time - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 18 [165] 21 [166] Units: msec     arithmetic mean (standard deviation) 209 ± 47 198 ± 54
Notes [165] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data [166] - 1 missing data
Statistical analysis title	Analysis DT - Baseline
Comparison groups	Placebo v Empagliflozin
Number of subjects included in analysis	39
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.61
Method	Wald test
Confidence interval

Post-hoc: Deceleration time - Baseline Top of page

Post-hoc: Deceleration time - Day 1 Top of page
End point title	Deceleration time - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 16 [167] 22 Units: msec     arithmetic mean (standard deviation) 212 ± 35 189 ± 45
Notes [167] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
Statistical analysis title	Analysis DT - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	38
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.234
Method	Wald test
Confidence interval

Post-hoc: Deceleration time - Day 1 Top of page

Post-hoc: Deceleration time - Day 3 Top of page
End point title	Deceleration time - Day 3
End point description
End point type	Post-hoc
End point timeframe	Day 3
End point values Empagliflozin Placebo Number of subjects analysed 16 [168] 22 Units: msec     arithmetic mean (standard deviation) 218 ± 42 202 ± 54
Notes [168] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data
Statistical analysis title	Analysis DT - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	38
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.624
Method	Wald test
Confidence interval

Post-hoc: Deceleration time - Day 3 Top of page

Post-hoc: Deceleration time - 3 Months Top of page
End point title	Deceleration time - 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 [169] 22 Units: msec     arithmetic mean (standard deviation) 213 ± 61 196 ± 59
Notes [169] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 2 missing data
Statistical analysis title	Analysis DT - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	40
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.261
Method	Wald test
Confidence interval

Post-hoc: Deceleration time - 3 Months Top of page

Post-hoc: Global longitudinal strain - Baseline Top of page
End point title	Global longitudinal strain - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 16 [170] 21 [171] Units: none     arithmetic mean (standard deviation) -19 ± 4.1 -17 ± 5.3
Notes [170] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data [171] - 1 missing data
Statistical analysis title	Analysis GLS - Baseline
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.107
Method	Wald test
Confidence interval

Post-hoc: Global longitudinal strain - Baseline Top of page

Post-hoc: Global longitudinal strain - Day 1 Top of page
End point title	Global longitudinal strain - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 16 [172] 21 [173] Units: none     arithmetic mean (standard deviation) -19 ± 3.4 -17 ± 4.8
Notes [172] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data [173] - 1 missing data
Statistical analysis title	Analysis GLS - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.877
Method	Wald test
Confidence interval

Post-hoc: Global longitudinal strain - Day 1 Top of page

Post-hoc: Global longitudinal strain - Day 3 Top of page
End point title	Global longitudinal strain - Day 3
End point description
End point type	Post-hoc
End point timeframe	Day 3
End point values Empagliflozin Placebo Number of subjects analysed 16 [174] 21 [175] Units: none     arithmetic mean (standard deviation) -19 ± 3.7 -17 ± 4.4
Notes [174] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data [175] - 1 missing data
Statistical analysis title	Analysis GLS - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.735
Method	Wald test
Confidence interval

Post-hoc: Global longitudinal strain - Day 3 Top of page

Post-hoc: Global longitudinal strain - 3 Months Top of page
End point title	Global longitudinal strain - 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 [176] 21 [177] Units: none     arithmetic mean (standard deviation) -19 ± 2.7 -17 ± 4.6
Notes [176] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 4 missing data [177] - 1 missing data
Statistical analysis title	Analysis GLS - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	37
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.608
Method	Wald test
Confidence interval

Post-hoc: Global longitudinal strain - 3 Months Top of page

Post-hoc: Right ventricular systolic pressure - Baseline Top of page
End point title	Right ventricular systolic pressure - Baseline
End point description
End point type	Post-hoc
End point timeframe	Baseline
End point values Empagliflozin Placebo Number of subjects analysed 12 [178] 11 [179] Units: mmHg     arithmetic mean (standard deviation) 29 ± 4 28 ± 6
Notes [178] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 8 missing data [179] - 11 missing data
Statistical analysis title	Analysis RVSP - Baseline
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	23
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.515
Method	Wald test
Confidence interval

Post-hoc: Right ventricular systolic pressure - Baseline Top of page

Post-hoc: Right ventricular systolic pressure - Day 1 Top of page
End point title	Right ventricular systolic pressure - Day 1
End point description
End point type	Post-hoc
End point timeframe	Day 1
End point values Empagliflozin Placebo Number of subjects analysed 10 [180] 12 [181] Units: mmHg     arithmetic mean (standard deviation) 26 ± 6 26 ± 5
Notes [180] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 10 missing data [181] - 10 missing data
Statistical analysis title	Analysis RVSP - Day 1
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	22
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.827
Method	Wald test
Confidence interval

Post-hoc: Right ventricular systolic pressure - Day 1 Top of page

Post-hoc: Right ventricular systolic pressure - Day 3 Top of page
End point title	Right ventricular systolic pressure - Day 3
End point description
End point type	Post-hoc
End point timeframe	Day 3
End point values Empagliflozin Placebo Number of subjects analysed 11 [182] 12 [183] Units: mmHg     arithmetic mean (standard deviation) 29 ± 10 25 ± 4
Notes [182] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 9 missing data [183] - 10 missing data
Statistical analysis title	Analysis RVSP - Day 3
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	23
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.261
Method	Wald test
Confidence interval

Post-hoc: Right ventricular systolic pressure - Day 3 Top of page

Post-hoc: Right ventricular systolic pressure - 3 Months Top of page
End point title	Right ventricular systolic pressure - 3 Months
End point description
End point type	Post-hoc
End point timeframe	3 Months
End point values Empagliflozin Placebo Number of subjects analysed 12 [184] 8 [185] Units: mmHg     arithmetic mean (standard deviation) 26 ± 11 27 ± 8
Notes [184] - 2 subjects were retrospectively excluded from analysis due to protocol deviations; 8 missing data [185] - 14 missing data
Statistical analysis title	Analysis RVSP - 3 Months
Comparison groups	Empagliflozin v Placebo
Number of subjects included in analysis	20
Analysis specification	Post-hoc
Analysis type	superiority
P-value	= 0.632
Method	Wald test
Confidence interval

Post-hoc: Right ventricular systolic pressure - 3 Months Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	3 Months
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	none
Dictionary version	0
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.
Serious adverse events Empagliflozin Placebo Total subjects affected by serious adverse events      subjects affected / exposed 4 / 22 (18.18%) 1 / 22 (4.55%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events 0 0 Injury, poisoning and procedural complications Hematoma in freshly operated knee with suspected inflammation      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Fall from roof with hospitalization for polytrauma      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Vascular disorders Syncope      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Hypotonia      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Small segmental pulmonary emboli      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Short reanimation      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Nervous system disorders Vigilance reduction & neurological symptoms      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Blood and lymphatic system disorders Hospitalization for clarification of the Hb drop      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 General disorders and administration site conditions Discomfort      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Hepatobiliary disorders Acute cholecystitis with stationary gallbladder surgery      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Multiple fractures      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Metabolism and nutrition disorders Hyponatremia      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events Empagliflozin Placebo Total subjects affected by non serious adverse events      subjects affected / exposed 19 / 22 (86.36%) 17 / 22 (77.27%) Vascular disorders Edema      subjects affected / exposed 3 / 22 (13.64%) 3 / 22 (13.64%)      occurrences all number 3 3 Orthostatic hypotension      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Pale skin color      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Surgical and medical procedures Planned outpatient meniscus knee surgery      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Reproductive system and breast disorders Gynecomastia      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Respiratory, thoracic and mediastinal disorders Bronchitis      subjects affected / exposed 1 / 22 (4.55%) 1 / 22 (4.55%)      occurrences all number 1 1 Psychiatric disorders Depressive Mood      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Injury, poisoning and procedural complications Scratch marks after gardening      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Cardiac disorders Aggravation of chronic right heart strain      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Asymptomatic AV block grade IIa Wenkebach      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 AV block grade I      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Hypertensive emergency with chest pain      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 left ventricular thrombus on ultrasound cardiogram      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 NT-proBNP increase      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Nervous system disorders Tingling      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Blood and lymphatic system disorders Blood Eosinophilia of unknown origin      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Hb drop of unclear origin      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Leucocytosis      subjects affected / exposed 1 / 22 (4.55%) 2 / 22 (9.09%)      occurrences all number 1 2 Gastrointestinal disorders Diarrhoea      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Gastroenteritis      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Hepatobiliary disorders Cholecystothiliasis      subjects affected / exposed 2 / 22 (9.09%) 1 / 22 (4.55%)      occurrences all number 2 1 Newly diagnosed liver cirrhosis on sonography, without elevation of liver enzymes      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Steatosis hepatis      subjects affected / exposed 3 / 22 (13.64%) 4 / 22 (18.18%)      occurrences all number 3 4 Skin and subcutaneous tissue disorders Balantitis      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 2 0 Change of fingernails      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Generalized pruritus in the genital area      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Renal and urinary disorders increased urge to urinate      subjects affected / exposed 3 / 22 (13.64%) 1 / 22 (4.55%)      occurrences all number 3 1 Musculoskeletal and connective tissue disorders Arthritis      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Back pain      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Herniated disc (recurrent)      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Infections and infestations Cold      subjects affected / exposed 2 / 22 (9.09%) 1 / 22 (4.55%)      occurrences all number 2 1 Fungal infection vagina      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 Metabolism and nutrition disorders Cramps in the lower leg with lactic acidosis      subjects affected / exposed 0 / 22 (0.00%) 1 / 22 (4.55%)      occurrences all number 0 1 Excessive thirst      subjects affected / exposed 2 / 22 (9.09%) 0 / 22 (0.00%)      occurrences all number 2 0 hypercalcemia of unknown origin      subjects affected / exposed 1 / 22 (4.55%) 0 / 22 (0.00%)      occurrences all number 1 0 increased blood sugar level      subjects affected / exposed 1 / 22 (4.55%) 8 / 22 (36.36%)      occurrences all number 2 18 lowered blood glucose level      subjects affected / exposed 2 / 22 (9.09%) 2 / 22 (9.09%)      occurrences all number 5 3

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
24 Oct 2017	Additional echocardiography at visit 3 & 4, addition of liver ultrasonography, 24 h blood pressure and 24 h collected urine measurement already performed at screening instead of baseline and omitted at visit 4
02 Mar 2018	Extension of the recruitment for 12 months
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

More information Top of page