Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Empagliflozin on Cardiac Structure, Function, and Circulating Biomarkers in Patients With Type 2 Diabetes
Brief Summary: The purpose of this study is to evaluate the effects of Empagliflozin on cardiac structure, function and circulating biomarkers in patients with Type II diabetes. Empagliflozin (anti-hyperglycemic agent), approved by Health Canada and the FDA for the treatment of Type II diabetes, demonstrated a reduction in cardiovascular deaths and heart failure from a previous post-marketing clinical trial. The use of empagliflozin to treat patients with diabetes and heart disease has been approved by Health Canada. However, the process by which it may give this beneficial effect remains unclear and needs further investigation. Therefore, the aim of this study is to provide a fundamental understanding of the mechanistic basis by which Empagliflozin could provide its potential cardio-protective effects by employing the use of Cardiac Magnetic Resonance Imaging (CMRI).


Options:
A: Inclusion Criteria:

* Male and female subjects ≥40 and ≤ 80 years of age
* History of type 2 diabetes
* Haemoglobin A1C ≥6.5 and ≤10 % within 3 months of the Screening Visit
* Established cardiovascular disease, defined as previous myocardial infarction ≥ 6 months ago, or previous coronary revascularization ≥ 2 months ago
* Any background antihyperglycemic therapy (which has been stable for at least 2 months)
* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial
* Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

Exclusion Criteria:

* Female subjects who are pregnant, lactating or of child bearing potential, or pre-menopausal women. (Menopause will be determined by patient and physician history)
* Type 1 diabetes
* Subjects currently treated with SGLT2 inhibitors, Glucagon-like peptide-1 (GLP1) receptor agonist, or saxagliptin
* Frequent episodes (\>4/month) of moderate hypoglycaemia, as defined by the Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes
* Any episode of severe hypoglycaemia within the past 12 months, as also defined by the Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes
* Subjects in whom coronary revascularisation by either Percutaneous coronary intervention (PCI) or bypass surgery is being contemplated within 6 months, or who have undergone revascularisation in the prior 2 months
* Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate (eGFR)\< 60 ml/min/1.73 m2 at screening
* Significant allergy or known intolerance to SGLT2 inhibitors or any ingredient in the formulations
* Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatologic disease, haematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease and psychiatric disease
* Any malignancy not considered cured (except basal cell carcinoma of the skin). A subject is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening
* Blood donation within 4 weeks prior to screening, or stated intention to donate blood or blood products during the period of the study or within one month following completion of the study
* Subjects who have participated in studies of an investigational drug or device within 30 days prior to the screening visit
* Conditions preventing safe MRI imaging such as the subject's weight exceeding 500 lbs; maximum body dimension from side-to-side exceeding 70 cm and from back to front of torso exceeding 50 cm or the presence of metallic fragments, clips or devices
* LVEF \<30% on the most recent assessment within 6 months
* New York Heart Association (NYHA) Class IV or recent hospitalization for decompensated Heart Failure (HF) (\<3 months)
* Unstable coronary syndromes
* Moderate or severe aortic stenosis
* Moderate or severe aortic regurgitation
* Moderate or severe mitral stenosis
* Moderate or severe mitral regurgitation
B: Inclusion Criteria:

* Patients with T2DM, diagnosed at least 3 months prior to Visit 1
* CHF (NYHA Class I, Class II, or Class III) at Visit 1
* LVEF \< 40%

Exclusion Criteria:

* Pregnant or lactating female
* FPG ≥ 270 mg/dL (≥15 mmol/L)
C: Inclusion criteria:

1. Type 2 diabetes
2. Elevated glycosylated haemoglobin (HbA1c): 6.5 - 8.5%, inclusive, if treatment naïve or mono-/dual therapy with metformin and/or an alpha-glucosidase inhibitor; 6.5 - 7.5%, inclusive, if treatment with sulphonylurea/glinide in mono- or dual (with metformin OR an alpha-glucosidase inhibitor) therapy)
3. Pre-existing cardiovascular disease OR specified diabetes end-organ damage OR age =\> 70 years OR two or more specified cardiovascular risk factor
4. BMI =\< 45kg/m²
5. age between \>= 40 and =\< 85 years
6. signed and dated written International Conference of Harmonisation( ICF)
7. stable anti-diabetic background for at least 8 wks before study start

Exclusion criteria:

1. Type 1 diabetes
2. Treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, Glucagon-like peptide 1 (GLP-1) analogue/agonists, Dipeptidyl-peptidase IV (DPP-IV) inhibitors or any insulin) prior to informed consent (previous short term use of insulin (up to two weeks) is allowed if taken at least 8 weeks prior informed consent)
3. treatment with any anti-obesity drug less than 3 months before ICF
4. uncontrolled hyperglycemia
5. previous or planned bariatric surgery or intervention
6. current or planned system corticoid treatment
7. change in thyroid hormones treatment
8. acute liver disease or impaired hepatic function
9. pre-planned coronary artery revascularization within 6 months of ICF
10. known hypersensitivity to any of the components
11. Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information
12. congestive heart failure class III or IV
13. acute or chronic metabolic acidosis
14. hereditary galactose intolerance
15. alcohol or drug abuse
16. participation in another trail with IMP given 2 months before Investigational Medicinal/Medical Product (IMP) start
17. pre-menopausal women who are nursing or pregnant or of child-bearing potential and not willing to use acceptable method of birth control
18. patients considered reliable by the investigator
19. acute coronary syndrome =\< 6 wks before ICF
20. stroke or Transient Ischemic Attack (TIA) =\< 3 months prior to ICF
D: Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone or with metformin and one other oral antidiabetic drug
2. Glycosylated haemoglobin (HbA1c) 6.0 - 9.0% at screening for patients treated with metformin and one other oral antidiabetic drug
3. HbA1c 6.5 - 10.0% at screening for patients treated with metformin alone
4. HbA1c 6.5 - 10.0% at beginning of the placebo run-in phase

Exclusion criteria:

1. Myocardial infarction, stroke or transient ischemic attack (TIA)
2. Impaired hepatic function
3. Renal failure or renal impairment
4. Treatment with rosiglitazone or pioglitazone within 6 months prior to screening
5. Treatment with insulin or glucagon-like peptide 1 (GLP-1) analogue/antagonists within 3 months prior to screening

Answer: A