Title

SGLT-2 Inhibitor and Myocardial Perfusion, Function and Metabolism in T2 DM Patients at High Cardiovascular Risk
Effects of SGLT-2 Inhibitor on Myocardial Perfusion, Function and Metabolism in Type 2 DM Patients at High Cardiovascular Risk: The SIMPle Randomized Clinical Trial
  • Phase

    Phase 3
  • Study Type

    Interventional
  • Status

    Unknown status
  • Intervention/Treatment

    empagliflozin ...
  • Study Participants

    92
Patients with type 2 diabetes (T2 DM) have a markedly increased risk of heart disease and it is estimated that, in the danish population, up 80% percent of patients with type 2 diabetes die from heart disease.

The sodium glucose cotransport-2 (SGLT-2) inhibitors were developed as an anti-diabetic therapy reducing blood glucose and weight by decreasing glucose reabsorption in the kidneys, leading to glucose excretion via the urine. However, in 2015 the EMPA-REG study showed that treatment with the SGLT-2 inhibitor empagliflozin significantly reduced the cardiovascular mortality and risk of admission under the diagnosis of heart failure in a population of patients with type 2 diabetes in addition to other risk factors for heart disease. The mechanism behind this surprising result is unknown and warrants further study.

The primary hypothesis of the present study is that treatment with empagliflozin improves the function and blood supply of the heart muscle cells in patients with type 2 diabetes and high risk of heart disease. The investigators will test this hypothesis by enrolling 92 participants with type 2 diabetes and other risk factors for heart disease, and treating them with either empagliflozin or a placebo. During the study period the investigators will monitor the effects of the treatment with various techniques such as heart scans using CT and ultrasound, measurements of the fluid pressures in the heart chambers, body composition measurements and a variety of relevant blood test.
Study Started
Mar 29
2017
Primary Completion
Jun 30
2020
Anticipated
Study Completion
Sep 30
2020
Anticipated
Last Update
Jun 30
2020

Drug Empagliflozin

Empagliflozin tablet

  • Other names: Jardiance

Drug Placebo Oral Tablet

Sugar pill, visually identical to active comparator

Empagliflozin Experimental

Empagliflozin, coated tablets, 25mg, once daily, for 13 weeks

Placebo Placebo Comparator

Placebo, coated tablets, once daily, for 13 weeks

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
No Results Posted