Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

A diagnosis of type 2 diabetes mellitus at least 3 months prior to baseline visit
For patients on background therapy: stable dose of anti-diabetics within 30 days prior to baseline
HbA1c of ≥6.5% and ≤10% at screening for patients on background therapy or HbA1c of ≥6.5 % and ≤ 9.0% at screening for drug-naïve patients.
BMI ≤ 45 kg/m2 at screening
Age ≥18 years
Negative pregnancy test (fertile women). Fertile women must use safe contraceptives (spiral, hormonal contraceptives) for the duration of the study
Able to understand the written patient information and to give informed consent
Patients must have high cardiovascular risk, defined as at least one of the following:
Albuminuria ( albumin/creatinine ratio ≥ 30 mg/g or plasma NT-proBNP ≥ 70 pg/ml)
Confirmed history of myocardial infarction (>2 months prior to baseline)
Heart failure according to the Framingham Heart Failure Criteria
Or patient discharged from hospital with a documented diagnosis of unstable angina within 12 months prior to baseline
Evidence of coronary artery disease by CAG in 1 or more major coronary arteries

OR at least one of the following: a positive noninvasive stress test, or A positive stress echocardiography showing regional systolic wall motion abnormalities, or A positive scintigraphic test showing stress-induced ischemia,

History of ischemic or haemorrhagic stroke (>2 months prior to informed consent)
Presence of peripheral artery disease (symptomatic or not ) documented by either: previous limb angioplasty, stenting or bypass surgery; or previous limb or foot amputation due to circulatory insufficiency; or angiographic evidence of significant (> 50%) peripheral artery stenosis in at least one limb; or evidence from a non-invasive measurement of significant (>50% or as reported as hemodynamically significant) peripheral artery stenosis in at least one limb; or ankle brachial index of < 0.9

Exclusion Criteria:

Allergic to the study medication
Treatment with SGLT-2 inhibitor within 3 months prior to baseline
Impaired kidney function, eGFR ≤ 30 ml/min
Severe liver insufficiency (Child-Pugh class C)
ECG showing malign ventricular arrhythmia or prolonged QT-interval (>500ms)
Untreated clinical significant heart valve disease
Planned cardiac surgery or angioplasty within 3 months.
Myocardial infarction (MI) ≤ 30 days prior to baseline
Percutaneous coronary intervention (PCI) ≤ 4 weeks prior to baseline
History of coronary artery bypass graft (CABG) ≤ 8 weeks prior to enrollment
Prior history of heart transplantation
Unstable angina, known severe left main coronary artery stenosis, severe heart failure, uncontrolled arrhythmias, symptomatic hypotension or severe hypertension (systolic blood pressure < 90 or > 180 mmHg, respectively), sick sinus syndrome or > 1st degree atrioventricular block in the absence of a functioning pacemaker
Requirement of emergent cardiac medical intervention or catheterization
Treatment with theophylline, or theophylline containing medications
History of known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)
Pregnancy or desire hereof or breastfeeding.

Additional exclusion criteria for hemodynamics substudy

LVEF ≤ 40 % evaluated at baseline echocardiography
Inability to perform a VO2 max test
Hypertrophic cardiomyopathy
Left ventricular assist device