Trial Outcomes & Findings for Empagliflozin Impact on Hemodynamics in Patients With Heart Failure (NCT NCT03030222)

Last Updated: 2021-12-09

Results Overview

Change in pulmonary artery diastolic pressure from baseline to end of treatment period (defined as average of pulmonary artery diastolic pressure measurements between weeks 8-12) between empagliflozin and placebo

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

65 participants

Primary outcome timeframe

Baseline to average between Weeks 8-12

Results posted on

2021-12-09

Participant Flow

Participant milestones

Participant milestones
Measure	Empagliflozin Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Overall Study STARTED	33	32
Overall Study COMPLETED	33	32
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Insulin use among patients with type 2 diabetes.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo	Total n=65 Participants Total of all reporting groups
Age, Continuous	69.5 years STANDARD_DEVIATION 12.0 • n=33 Participants	62.9 years STANDARD_DEVIATION 13.3 • n=32 Participants	66.2 years STANDARD_DEVIATION 12.9 • n=65 Participants
Sex: Female, Male Female	12 Participants n=33 Participants	12 Participants n=32 Participants	24 Participants n=65 Participants
Sex: Female, Male Male	21 Participants n=33 Participants	20 Participants n=32 Participants	41 Participants n=65 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=33 Participants	0 Participants n=32 Participants	0 Participants n=65 Participants
Race (NIH/OMB) Asian	0 Participants n=33 Participants	0 Participants n=32 Participants	0 Participants n=65 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=33 Participants	0 Participants n=32 Participants	0 Participants n=65 Participants
Race (NIH/OMB) Black or African American	5 Participants n=33 Participants	7 Participants n=32 Participants	12 Participants n=65 Participants
Race (NIH/OMB) White	27 Participants n=33 Participants	23 Participants n=32 Participants	50 Participants n=65 Participants
Race (NIH/OMB) More than one race	0 Participants n=33 Participants	0 Participants n=32 Participants	0 Participants n=65 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=33 Participants	2 Participants n=32 Participants	3 Participants n=65 Participants
Region of Enrollment United States	33 participants n=33 Participants	32 participants n=32 Participants	65 participants n=65 Participants
Duration of Heart Failure	5.4 years STANDARD_DEVIATION 5.7 • n=33 Participants	7.2 years STANDARD_DEVIATION 5.5 • n=32 Participants	6.3 years STANDARD_DEVIATION 5.6 • n=65 Participants
Prior hospitalization for heart failure	29 Participants n=33 Participants	28 Participants n=32 Participants	57 Participants n=65 Participants
Time since last hospitalization for heart failure	1.3 years STANDARD_DEVIATION 0.9 • n=33 Participants	1.5 years STANDARD_DEVIATION 1.4 • n=32 Participants	1.4 years STANDARD_DEVIATION 1.2 • n=65 Participants
Ejection fraction	46.7 % STANDARD_DEVIATION 14.9 • n=33 Participants	40.7 % STANDARD_DEVIATION 17.2 • n=32 Participants	43.7 % STANDARD_DEVIATION 16.2 • n=65 Participants
Ischemic heart disease	13 Participants n=33 Participants	10 Participants n=32 Participants	23 Participants n=65 Participants
Type 2 Diabetes	18 Participants n=33 Participants	16 Participants n=32 Participants	34 Participants n=65 Participants
Atrial Fibrillation	20 Participants n=33 Participants	17 Participants n=32 Participants	37 Participants n=65 Participants
Implantable cardioverter defibrillator (ICD)	15 Participants n=33 Participants	21 Participants n=32 Participants	36 Participants n=65 Participants
Cardiac resynchronization therapy (CRT)	13 Participants n=33 Participants	8 Participants n=32 Participants	21 Participants n=65 Participants
Pulmonary Artery Diastolic Pressure	23.3 mm Hg STANDARD_DEVIATION 6.9 • n=33 Participants	20.5 mm Hg STANDARD_DEVIATION 5.7 • n=32 Participants	21.9 mm Hg STANDARD_DEVIATION 6.4 • n=65 Participants
Angiotensin-converting enzyme inhibitor / Angiotensin II receptor blocker (ACEI/ARB)	11 Participants n=33 Participants	8 Participants n=32 Participants	19 Participants n=65 Participants
Angiotensin receptor-neprilysin inhibitor (ARNI)	13 Participants n=33 Participants	17 Participants n=32 Participants	30 Participants n=65 Participants
Beta blockers	29 Participants n=33 Participants	29 Participants n=32 Participants	58 Participants n=65 Participants
Hydralazine	7 Participants n=33 Participants	3 Participants n=32 Participants	10 Participants n=65 Participants
Long-acting nitrates	15 Participants n=33 Participants	9 Participants n=32 Participants	24 Participants n=65 Participants
Mineralocorticoid receptor antagonist (MRA)	9 Participants n=33 Participants	20 Participants n=32 Participants	29 Participants n=65 Participants
Loop diuretics	31 Participants n=33 Participants	32 Participants n=32 Participants	63 Participants n=65 Participants
Digoxin	6 Participants n=33 Participants	3 Participants n=32 Participants	9 Participants n=65 Participants
Lipid lowering agent	27 Participants n=33 Participants	23 Participants n=32 Participants	50 Participants n=65 Participants
Anticoagulant agent	16 Participants n=33 Participants	13 Participants n=32 Participants	29 Participants n=65 Participants
Body Mass Index	33.5 kg/m^2 n=33 Participants	33.8 kg/m^2 n=32 Participants	33.5 kg/m^2 n=65 Participants
Heart rate	70.1 bpm STANDARD_DEVIATION 10.2 • n=33 Participants	72.6 bpm STANDARD_DEVIATION 9.8 • n=32 Participants	71.3 bpm STANDARD_DEVIATION 10 • n=65 Participants
Systolic Blood Pressure	128.3 mm Hg STANDARD_DEVIATION 19.1 • n=33 Participants	120.7 mm Hg STANDARD_DEVIATION 20.3 • n=32 Participants	124.5 mm Hg STANDARD_DEVIATION 19.9 • n=65 Participants
N-terminal pro b-type natriuretic peptide (NT-proBNP)	865.5 pg/mL n=33 Participants	563.5 pg/mL n=32 Participants	637.0 pg/mL n=65 Participants
Brain natriuretic peptide (BNP)	140.0 pg/mL n=33 Participants	129.0 pg/mL n=32 Participants	140 pg/mL n=65 Participants
Estimated glomerular filtration rate (eGFR)	51.2 mL/min/1.73m^2 STANDARD_DEVIATION 19.7 • n=33 Participants	62.7 mL/min/1.73m^2 STANDARD_DEVIATION 25.5 • n=32 Participants	56.9 mL/min/1.73m^2 STANDARD_DEVIATION 23.3 • n=65 Participants
Urine Albumin/Creatinine Ratio	101.9 mg/g STANDARD_DEVIATION 187.4 • n=33 Participants	201.6 mg/g STANDARD_DEVIATION 688.2 • n=32 Participants	149.3 mg/g STANDARD_DEVIATION 491.1 • n=65 Participants
Hemoglobin A1c (HbA1c)	6.4 percentage of hemoglobin STANDARD_DEVIATION 1.3 • n=33 Participants	6.9 percentage of hemoglobin STANDARD_DEVIATION 1.9 • n=32 Participants	6.6 percentage of hemoglobin STANDARD_DEVIATION 1.6 • n=65 Participants
Hemoglobin	13.3 g/dL STANDARD_DEVIATION 2.1 • n=33 Participants	12.5 g/dL STANDARD_DEVIATION 1.6 • n=32 Participants	12.9 g/dL STANDARD_DEVIATION 1.9 • n=65 Participants
New York Heart Association (NYHA) Class II	14 Participants n=33 Participants	16 Participants n=32 Participants	30 Participants n=65 Participants
New York Heart Association (NYHA) Class III	18 Participants n=33 Participants	16 Participants n=32 Participants	34 Participants n=65 Participants
Kansas City Cardiomyopathy Questionnaire - Overall Summary Score (KCCQ-OS)	60.5 points STANDARD_DEVIATION 16.9 • n=33 Participants	61.1 points STANDARD_DEVIATION 27.2 • n=32 Participants	60.8 points STANDARD_DEVIATION 22.4 • n=65 Participants
Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CS)	60.2 points STANDARD_DEVIATION 18.7 • n=33 Participants	64.6 points STANDARD_DEVIATION 26.4 • n=32 Participants	62.4 points STANDARD_DEVIATION 22.8 • n=65 Participants
6-minute walk distance	237.7 meters n=33 Participants	232.1 meters n=32 Participants	233.2 meters n=65 Participants
Insulin (among patients with type 2 diabetes)	11 Participants n=18 Participants • Insulin use among patients with type 2 diabetes.	11 Participants n=16 Participants • Insulin use among patients with type 2 diabetes.	22 Participants n=34 Participants • Insulin use among patients with type 2 diabetes.
Glucagon-like peptide-1 receptor agonist (GLP-1 RA )(among patients with type 2 diabetes)	3 Participants n=18 Participants • GLP-1RA use among patients with type 2 diabetes.	4 Participants n=16 Participants • GLP-1RA use among patients with type 2 diabetes.	7 Participants n=34 Participants • GLP-1RA use among patients with type 2 diabetes.
Dipeptidyl-peptidase 4 (DPP4) inhibitor (among patients with type 2 diabetes)	2 Participants n=18 Participants • DPP4-inhibitor use among patients with type 2 diabetes.	2 Participants n=16 Participants • DPP4-inhibitor use among patients with type 2 diabetes.	4 Participants n=34 Participants • DPP4-inhibitor use among patients with type 2 diabetes.
Sulfonylurea (among patients with type 2 diabetes)	2 Participants n=18 Participants • Sulfonylurea use among patients with type 2 diabetes.	1 Participants n=16 Participants • Sulfonylurea use among patients with type 2 diabetes.	3 Participants n=34 Participants • Sulfonylurea use among patients with type 2 diabetes.

PRIMARY outcome

Timeframe: Baseline to average between Weeks 8-12

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in Pulmonary Artery Diastolic Pressure From Baseline to End of Treatment Period (Defined as Average of Pulmonary Artery Diastolic Pressure Measurements Between Weeks 8-12) Between Empagliflozin and Placebo	20.7 mm Hg Interval 19.6 to 21.7	22.2 mm Hg Interval 21.1 to 23.2

SECONDARY outcome

Timeframe: Baseline to Weeks 1-12

Change from baseline in pulmonary artery diastolic pressure at each interim timepoint (wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 0	21.2 mm Hg Interval 20.4 to 22.1	21.4 mm Hg Interval 20.5 to 22.2
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 1	21.2 mm Hg Interval 20.4 to 21.9	21.5 mm Hg Interval 20.7 to 22.3
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 2	21.1 mm Hg Interval 20.3 to 21.9	21.7 mm Hg Interval 20.9 to 22.4
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 3	21.1 mm Hg Interval 20.2 to 21.9	21.8 mm Hg Interval 20.9 to 22.6
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 4	21.0 mm Hg Interval 20.1 to 22.0	21.9 mm Hg Interval 21.0 to 22.8
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 5	21.0 mm Hg Interval 20.1 to 22.0	22.0 mm Hg Interval 21.0 to 23.0
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 6	21.0 mm Hg Interval 20.0 to 22.0	22.1 mm Hg Interval 21.1 to 23.1
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 7	21.0 mm Hg Interval 19.9 to 22.0	22.1 mm Hg Interval 21.1 to 23.2
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 8	21.0 mm Hg Interval 19.8 to 22.0	22.2 mm Hg Interval 21.1 to 23.2
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 9	20.8 mm Hg Interval 19.7 to 21.9	22.2 mm Hg Interval 21.1 to 23.3
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 10	20.7 mm Hg Interval 19.6 to 21.8	22.2 mm Hg Interval 21.1 to 23.3
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 11	20.5 mm Hg Interval 19.5 to 21.6	22.2 mm Hg Interval 21.0 to 23.3
Change From Baseline in Pulmonary Artery Diastolic Pressure at Each Interim Timepoint (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12) Between Empagliflozin and Placebo. Pulmonary artery diastolic pressure - Week 12	20.4 mm Hg Interval 19.2 to 21.6	22.1 mm Hg Interval 20.9 to 23.3

SECONDARY outcome

Timeframe: Baseline to Week 12

Change in pulmonary artery systolic pressure from baseline to end of treatment period (week 12) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in Pulmonary Artery Systolic Pressure From Baseline to End of Treatment Period (Week 12) Between Empagliflozin and Placebo.	20.4 mm Hg Interval 19.2 to 21.6	22.1 mm Hg Interval 20.9 to 23.3

SECONDARY outcome

Timeframe: Baseline to Weeks 1-12

Change from baseline in pulmonary artery systolic pressure at each interim time point (wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 0	44.1 mm Hg Interval 42.6 to 45.6	43.9 mm Hg Interval 42.4 to 45.3
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 1	44.1 mm Hg Interval 42.8 to 45.4	44.0 mm Hg Interval 42.7 to 45.2
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 2	44.1 mm Hg Interval 42.8 to 45.4	44.1 mm Hg Interval 42.8 to 45.3
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 3	44.1 mm Hg Interval 42.6 to 45.5	44.2 mm Hg Interval 42.7 to 45.6
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 4	44.0 mm Hg Interval 42.5 to 45.6	44.3 mm Hg Interval 42.7 to 45.8
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 5	44.0 mm Hg Interval 42.3 to 45.6	44.4 mm Hg Interval 42.8 to 46.0
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 6	44.0 mm Hg Interval 42.2 to 45.6	44.6 mm Hg Interval 42.9 to 46.3
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 7	43.8 mm Hg Interval 42.0 to 45.6	44.7 mm Hg Interval 42.9 to 46.5
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 8	43.7 mm Hg Interval 41.8 to 45.6	44.8 mm Hg Interval 42.9 to 46.8
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 9	43.6 mm Hg Interval 41.6 to 45.5	44.9 mm Hg Interval 42.9 to 46.9
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 10	43.4 mm Hg Interval 41.5 to 45.3	44.9 mm Hg Interval 43.0 to 46.9
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 11	43.3 mm Hg Interval 41.3 to 45.2	44.9 mm Hg Interval 43.0 to 46.9
Change From Baseline in Pulmonary Artery Systolic Pressure at Each Interim Time Point (Wks 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12) Between Empagliflozin and Placebo. Pulmonary artery systolic pressure - Week 12	43.1 mm Hg Interval 41.0 to 45.1	44.9 mm Hg Interval 42.8 to 46.9

SECONDARY outcome

Timeframe: Baseline to Week 12

Change in mean pulmonary artery pressure from baseline to end of treatment period (week 12) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in Mean Pulmonary Artery Pressure From Baseline to End of Treatment Period (Week 12) Between Empagliflozin and Placebo.	29.3 mm Hg Interval 27.9 to 30.8	31.1 mm Hg Interval 29.6 to 32.5

SECONDARY outcome

Timeframe: Baseline to Weeks 1-12

Change from baseline in mean pulmonary artery pressure at each interim time point (weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 0	30.1 mm Hg Interval 29.0 to 31.2	30.1 mm Hg Interval 29.0 to 31.2
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 1	30.1 mm Hg Interval 29.1 to 31.1	30.2 mm Hg Interval 29.2 to 31.2
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 2	30.1 mm Hg Interval 29.1 to 31.0	30.4 mm Hg Interval 29.4 to 31.4
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 3	30.0 mm Hg Interval 29.0 to 31.1	30.5 mm Hg Interval 29.5 to 31.6
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 4	30.0 mm Hg Interval 28.9 to 31.2	30.7 mm Hg Interval 29.5 to 31.8
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 5	30.0 mm Hg Interval 28.8 to 31.2	30.8 mm Hg Interval 29.6 to 32.0
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 6	30.0 mm Hg Interval 28.7 to 31.2	30.9 mm Hg Interval 29.7 to 32.2
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 7	29.9 mm Hg Interval 28.6 to 31.2	31.0 mm Hg Interval 29.7 to 32.3
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 8	29.9 mm Hg Interval 28.5 to 31.2	31.1 mm Hg Interval 29.7 to 32.4
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 9	29.8 mm Hg Interval 28.4 to 31.1	31.1 mm Hg Interval 29.7 to 32.5
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 10	29.6 mm Hg Interval 28.2 to 31.0	31.1 mm Hg Interval 29.8 to 32.5
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 11	29.5 mm Hg Interval 28.1 to 30.8	31.1 mm Hg Interval 29.7 to 32.5
Change From Baseline in Mean Pulmonary Artery Pressure at Each Interim Time Point (Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12) Between Empagliflozin and Placebo. Pulmonary artery pressure - Week 12	29.3 mm Hg Interval 27.9 to 30.8	31.1 mm Hg Interval 29.6 to 32.5

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the Kansas City Cardiomyopathy Questionnaire Overall Summary Score KCCQ-OS, a small but clinically meaningful change is considered to be ≥ 5 points.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in Heart Failure Related Quality of Life, Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) From Baseline to Follow-up (Defines as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) score - 6 weeks	63.5 score on a scale Interval 58.0 to 68.9	66.6 score on a scale Interval 61.0 to 72.2
Change in Heart Failure Related Quality of Life, Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) From Baseline to Follow-up (Defines as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) score - 12 weeks	64.2 score on a scale Interval 58.8 to 69.6	61.7 score on a scale Interval 56.2 to 67.3
Change in Heart Failure Related Quality of Life, Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) From Baseline to Follow-up (Defines as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) score - 6 weeks	66.6 score on a scale Interval 61.1 to 72.2	65.6 score on a scale Interval 60.0 to 71.3
Change in Heart Failure Related Quality of Life, Using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) From Baseline to Follow-up (Defines as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) score - 12 weeks	65.8 score on a scale Interval 60.3 to 71.2	60.2 score on a scale Interval 54.5 to 65.9

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Population: The number of participants analyzed may differ from the overall number of participants analyzed due to missing data at certain timepoints for some participants.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Proportion of Patients With a ≥ 5 Point Increase From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. KCCQ-OS score increase >/= 5 points (6 weeks)	13 Participants	15 Participants
Proportion of Patients With a ≥ 5 Point Increase From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. KCCQ-OS score increase >/= 5 points (12 weeks)	11 Participants	10 Participants
Proportion of Patients With a ≥ 5 Point Increase From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. KCCQ-CS score increase >/= 5 points (6 weeks)	13 Participants	10 Participants
Proportion of Patients With a ≥ 5 Point Increase From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. KCCQ-CS score increase >/= 5 points (12 weeks)	12 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Change in 6 minute walk test from baseline to follow-up (defined as average of measurements at 6 and 12 weeks) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in 6 Minute Walk Test From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. 6-minute walk distance - 6 weeks	202.5 meters Interval 170.9 to 239.8	211.2 meters Interval 177.0 to 252.0
Change in 6 Minute Walk Test From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. 6-minute walk distance - 12 weeks	217.4 meters Interval 183.3 to 257.9	174.7 meters Interval 146.6 to 208.0

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) from baseline to follow-up (defined as average of measurements at 6 and 12 weeks) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. NT-proBNP - 6 weeks	693 pg/mL Interval 556.0 to 865.0	655 pg/mL Interval 518.0 to 830.0
Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. NT-proBNP - 12 weeks	659 pg/mL Interval 528.0 to 822.0	802 pg/mL Interval 635.0 to 1013.0

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Change in brain natriuretic peptide (BNP) from baseline to follow-up (defined as average of measurements at 6 and 12 weeks) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in Brain Natriuretic Peptide (BNP) From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. BNP - 6 weeks	143 pg/mL Interval 113.0 to 180.0	149 pg/mL Interval 116.0 to 191.0
Change in Brain Natriuretic Peptide (BNP) From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. BNP - 12 weeks	144 pg/mL Interval 114.0 to 182.0	167 pg/mL Interval 130.0 to 214.0

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Population: The number of participants analyzed may differ from the overall number of participants analyzed due to missing data at certain timepoints for some participants.

Proportion of patients with a ≥ 20% decrease from baseline in N-terminal pro b-type natriuretic peptide (NT-proBNP) at either 6 weeks or 12 weeks of follow-up between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Proportion of Patients With a ≥ 20% Decrease From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. NT-proBNP decrease >/= 20% - 6 weeks	10 Participants	6 Participants
Proportion of Patients With a ≥ 20% Decrease From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. NT-proBNP decrease >/= 20% - 12 weeks	11 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Population: The number of participants analyzed may differ from the overall number of participants analyzed due to missing data at certain timepoints for some participants.

Proportion of patients with a ≥ 20% decrease from baseline in brain natriuretic peptide (BNP) at either 6 weeks or 12 weeks of follow-up between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Proportion of Patients With a ≥ 20% Decrease From Baseline in Brain Natriuretic Peptide (BNP) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. BNP decrease >/= 20% - 6 weeks	12 Participants	6 Participants
Proportion of Patients With a ≥ 20% Decrease From Baseline in Brain Natriuretic Peptide (BNP) at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo. BNP decrease >/= 20% - 12 weeks	11 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Proportion of patients with both a ≥ 5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) and a ≥ 20% decrease from baseline in N-terminal pro b-type natriuretic peptide (NT-proBNP) at either 6 weeks or 12 weeks of follow-up between empagliflozin and placebo. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. For the Kansas City Cardiomyopathy Questionnaire Overall Summary Score KCCQ-OS, a small but clinically meaningful change is considered to be ≥ 5 points.

Outcome measures

Outcome measures
Measure	Empagliflozin n=32 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=30 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Proportion of Patients With Both a ≥ 5 Point Increase From Baseline in KCCQ-OS and a ≥ 20% Decrease From Baseline in NT-proBNP at Either 6 Weeks or 12 Weeks of Follow-up Between Empagliflozin and Placebo.	19 Participants	14 Participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Number of Participants with Diuretic Medication Adjustments During the Treatment Period Between Empagliflozin and Placebo

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Number of Participants With Diuretic Medication Adjustments During the Treatment Period Between Empagliflozin and Placebo Number of patients with no loop diuretic changes	25 Participants	26 Participants
Number of Participants With Diuretic Medication Adjustments During the Treatment Period Between Empagliflozin and Placebo Number of patients with loop diuretic changes	8 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline to Week 6 and Week 12

Change in Hemoglobin A1c from baseline to follow-up (defined as average of measurements at 6 and 12 weeks) between empagliflozin and placebo.

Outcome measures

Outcome measures
Measure	Empagliflozin n=33 Participants Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 Participants Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Change in Hemoglobin A1c From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. Hemoglobin A1c - 6 weeks	6.6 percentage of hemoglobin Interval 6.3 to 6.9	6.5 percentage of hemoglobin Interval 6.2 to 6.8
Change in Hemoglobin A1c From Baseline to Follow-up (Defined as Average of Measurements at 6 and 12 Weeks) Between Empagliflozin and Placebo. Hemoglobin A1c - 12 weeks	6.8 percentage of hemoglobin Interval 6.5 to 7.1	6.3 percentage of hemoglobin Interval 6.1 to 6.6

Adverse Events

Empagliflozin

Serious events: 8 serious events

Other events: 19 other events

Deaths: 1 deaths

Placebo

Serious events: 9 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Manager

Saint Luke's Hospital of Kansas City

Phone: 816-932-9858

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Subsites will not publish until after all multicenter articles have been submitted for publication. Sponsor will have 18 months after the close of the Study at all sites to arrange for the submission of multicenter publications. If such multicenter publications are not submitted within 24 months after conclusion of the Study at all sites, Site Investigator and Subsite may publish the results from the Subsite's data, individually, pursuant to approval by Sponsor and Steering Committee.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Empagliflozin n=33 participants at risk Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 participants at risk Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
Cardiac disorders Exacerbation of Heart Failure	12.1% 4/33 • Number of events 4 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	12.5% 4/32 • Number of events 4 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Chest Pain	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Bronchitis	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Cellulitis	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Injury, poisoning and procedural complications Head Contusion	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Gastrointestinal disorders Esophagitis	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Groin Abcess	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Hematuria	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Hypotension	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Musculoskeletal and connective tissue disorders Osteoarthritis - left knee	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Sepsis	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Volume Depletion	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Worsening Tricuspid Valve Regurgitation	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Endocarditis	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Ventricular Tachycardia	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Pneumonia	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders CardioMEMS device recalibration	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Myocardial Infarction	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.

Other adverse events
Measure	Empagliflozin n=33 participants at risk Empagliflozin 10 mg tab, once daily, for 12 weeks Empagliflozin 10 mg Tab: Empagliflozin 10 mg Tab	Placebo n=32 participants at risk Empagliflozin matching placebo oral tablet, once daily for 12 weeks Placebo Oral Tablet: Empagliflozin matching placebo
General disorders Acute Kidney Injury	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	6.2% 2/32 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Chest Pain	6.1% 2/33 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Cellulitis - bilateral legs	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Injury, poisoning and procedural complications Concussion	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Congestion	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Injury, poisoning and procedural complications Contusion - scalp	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Cough	6.1% 2/33 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Dysuria	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Exacerbation of Heart Failure	9.1% 3/33 • Number of events 3 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	9.4% 3/32 • Number of events 6 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Exertional Angina	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Gastrointestinal disorders Gastritis	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Gastrointestinal disorders Gastroenteritis	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Gout Flare	3.0% 1/33 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	6.2% 2/32 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Hiccups	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Endocrine disorders Asymptomatic hypoglycemia	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Hypokalemia	9.1% 3/33 • Number of events 4 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Cardiac disorders Hypotension	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Increased craving for sweets	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Malaise	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Pulmonary Nodule	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Quick Tempered	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Abscess - bilateral - hips, buttocks and upper legs	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Lower left extremity swelling	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Vaginal Yeast Infection	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Vertigo	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Volume Depletion	9.1% 3/33 • Number of events 3 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Worsening Gout	3.0% 1/33 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Wound Dehiscence	3.0% 1/33 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	0.00% 0/32 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Bilateral Handshaking	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Bloating	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Infections and infestations Bronchitis	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Bursitis - left knee	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Cerumen Impaction	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Chest Discomfort	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Decreased renal function	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Deep Vein Thrombosis	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
Gastrointestinal disorders Diarrhea	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Dizziness	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 2 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.
General disorders Dystrophic Toenails	0.00% 0/33 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.	3.1% 1/32 • Number of events 1 • Adverse events were collected for up to 15 weeks. The adverse event collection period started at the time the patient signed consent at their Screening Visit, continued through a 12-week double-blind treatment period after randomization, and ended after completion of a 1-week follow-up period after completion of the double-blind treatment period. All adverse events were collected including Serious Adverse Events, Drug Adverse Events, Adverse Events of Special Interest and Urgent Outpatient Heart Failure Visits. A Drug Adverse Events is an adverse event which leads to premature and permanent discontinuation of study drug. Adverse Events of Special Interest include diabetic ketoacidosis, volume depletion, severe hypoglycemic events and non-traumatic lower limb amputations.