Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of Empagliflozin (10mg, 25mg) Administered Orally, Once Daily Over 24 Weeks in Hypertensive Black/African American Patients With Type 2 Diabetes Mellitus
Brief Summary: This trial is designed to investigate the efficacy and safety of empagliflozin compared with placebo in hypertensive black/African Americans with type 2 Diabetes Mellitus. Since hyperglycaemia and hypertension are key risk factors for both micro- and macrovascular complications, assessment of both glucose and BP lowering effects of empagliflozin in hypertensive African American patients with type 2 Diabetes Mellitus could provide clinically highly relevant, new information for the use of empagliflozin.

Essential hypertension is four times more common in African Americans than in Caucasians.

One of the risk factors for hypertension is sodium sensitivity and approximately one third of the essential hypertensive population is responsive to sodium intake. There is a higher association of hypertension with sodium sensitivity in African American patients with type 2 Diabetes Mellitus.

The treatment duration of this trial (24 weeks) will enable assessment of the clinically relevant endpoint of a decrease in HbA1c, a well accepted measurement of chronic glycaemic control and the key secondary endpoints of decreases in systolic BP (SBP) and diastolic BP (DBP) at 12 and 24 weeks.


Options:
A: 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
B: Inclusion Criteria:

* Patients with type 2 diabetes with cardiovascular risk factors (\*) who treated with diet, exercise or antidiabetic medications
* Patients who were treated with statins for 8 weeks or longer
* Patients with low-density lipoprotein cholesterol equal to or greater than 100 mg/dL in the at least one of three measurements after the administration of statins
* Patients with glycerated hemoglobin (HbA1c, NGSP) equal to or greater than 6.0 % (7.0 % if patients were not treated with dipeptidyl-peptidase 4 inhibitors) and lesser than 10.5 %

(\*) cardiovascular risk factors were any of following conditions

1. Presence of stenosis (\>=25%) or plaque on the previous coronary angiography or coronary CT
2. Presence of coronary calcification on the previous coronary CT
3. History of acute coronary syndrome
4. History of percutaneous coronary intervention or coronary artery bypass graft
5. History of stroke (ischemic stroke or hemorrhagic stroke)
6. History of transient ischemic attack
7. History of peripheral artery diseases or aortic disorders
8. Ankle-Brachial Index (AMI) equal to or less than 0.9 in the past measurement
9. Presence of carotid artery plaque (including Max IMT \>=1.1mm) on carotid ultrasonography in the past

Exclusion Criteria:

* Patients with type 1 diabetes
* Patients with triglyceride equal to or greater than 400 mg/dL in the previous fasting measurements
* Patients with pregnancy, possible pregnancy, or on breast-feeding
* Patients with severe infections, perioperative status, or severe trauma
* Patients with renal dysfunction (creatinine \>= 2.4 mg/dl for men, \>= 2.0 mg/dl for women)
* Patients who were received glucagon-like peptide-1receptor agonists
* Patients whom physician in charge considered inappropriate for the study
C: Inclusion criteria:

* Diagnosis of Type 2 Diabetes Mellitus (T2DM) prior to informed consent.
* Male and female black/African American patients on diet and exercise regimen who are EITHER drug-naïve (defined as absence of any oral antidiabetic therapy, glucagon like peptide-1 (GLP-1) analog or insulin for 12 weeks, 16 weeks for pioglitazone prior to randomisation) OR pre-treated with stable dose of

  * Metformin only, or
  * Sulfonylurea only, or
  * Dipeptidyl peptidase-4 (DPP-4) inhibitor only, or
  * metformin plus sulfonylurea, or
  * metformin plus DPP-4 inhibitor. Treatment has to be unchanged for a minimum of 12 weeks prior to randomization. Dose for metformin: maximum tolerated dose The maximum daily dose of Sulfonylurea (SU) or DPP-4 inhibitor should not exceed that stated in the local label.
* HbA1c of \>= 7.0% (53 mmol/mol) and ≤ 11.0% (97 mmol/mol) at Visit 1 (screening).
* Mean seated Systolic Blood Pressure (SBP) 140-180 mmHg at Visit 1 (screening).
* Successful completion of baseline Ambulatory Blood Pressure Monitor (ABPM) testing with a mean SBP 135-175 mmHg prior to randomisation.
* Treatment with stable doses of at least one but not more than 4 antihypertensive medication \>= 4 weeks prior to randomisation.
* Age \>= 18 years at Visit 1 (screening)
* Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

* Uncontrolled hyperglycemia with a glucose level \>270 mg/dl (\>15.0 mmol/L) after an overnight fast during placebo run-in (includes Visit 2.1) and confirmed by a second measurement (not on the same day).
* Exposure to any other antidiabetic medication within 12 weeks prior to randomisation other than metformin, sulfonylurea, Dipeptidyl peptidase-4 (DPP-4) inhibitor, metformin plus sulfonylurea or metformin plus DPP-4 inhibitor.
* Current hypertension treatment with oral Minoxidil (topical minoxidil for hair growth is allowed).
* Mean seated Systolic Blood Pressure (SBP) ≥181 mmHg during placebo run-in visit and confirmed by a second measurement (not on the same day) preferably within one day.
* Upper arm circumference that exceeds the upper circumference level of the cuff size of either Ambulatory Blood Pressure Monitor (ABPM) and/or (BP) measurement device used in the study.
* Night shift workers who routinely sleep during the daytime and/or whose work hours include midnight.
* Diagnosis of autoimmune diabetes/Type I diabetes mellitus, monogenic (neonatal or maturity onset diabetes of the young (MODY)) diabetes or Type I diabetes in adults/latent autoimmune diabetes of adults (LADA) per investigator or patient medical history at the time of Visit 1 (screening).
* Known or suspected secondary hypertension (e.g. renal artery stenosis,phaeochromocytoma, Cushing's disease).
* History or evidence of hypertensive retinopathy (Keith-Wagener grade III or IV) and/or hypertensive encephalopathy.
* Clinically significant valvular heart disease or severe aortic stenosis in the opinion of the investigator.
* Acute coronary syndrome (non- ST wave elevated myocardial infarction (STEMI), STEMI and unstable angina pectoris), stroke or transient ischemic attack within 3 months prior to informed consent.
* Indication of liver disease, defined by serum levels of either Alanine Aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase(SGPT)), Aspartate Aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase.
* Impaired renal function, defined as Estimated Glomerular Filtration Rate (eGFR)\< 45 ml/min/1.73m2 (moderate renal impairment, chronic kidney disease epidemiology collaboration Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) as determined during screening and/or run-in phase.
* Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
* Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
* Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cells (e.g. malaria, babesiosis, haemolytic anaemia, thalassemia, sickle cell anaemia (sickle cell trait is allowed)).
* Medical history and signs and symptoms of diabetic autonomic neuropathy.
* Treatment with anti-obesity drugs 3 months prior to randomisation (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight.
* Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except Type 2 Diabetes Mellitus (T2DM) in the opinion of the investigator.
* Pre-menopausal women (last menstruation \<=1 year prior to informed consent) who:

  * are nursing or pregnant or
  * are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, complete sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner.
* Alcohol, drug or confectionary liquorice abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the investigator's opinion.
* Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial; or participating in another trial (involving an investigational drug and/or follow-up) after discontinuing medication in that trial.
* Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial in the opinion of the investigator.
D: Inclusion Criteria:

* Able to understand the written patient information and to give informed consent
* CHF, NYHA-class I, II or III at visit 0
* LVEF ≤45 %
* Age 30 to 85 (both inclusive)
* Stable pharmacological treatment of heart failure according to ESC guidelines for the last 3 months prior to randomisation (visit 1)

For patients with diabetes exclusively:

* T2D (WHO criteria), diagnosed at least 3 months prior to visit 0
* Patients with diabetes must be either untreated or treated with one or more oral anti-diabetic drugs or treated with human NPH-insulin or long-acting insulin analogue, alone or in combination with oral drugs
* Stable and optimal dose of anti diabetic treatment for 30 days prior to randomisation (visit 1)

Exclusion Criteria:

* Myocardial infarction (MI), unstable angina or coronary revascularization within the last three months prior to visit 1
* Hospitalisation due to incompensated heart disease within 30 days prior to randomisation (visit 1)
* CHF (NYHA class IV)
* ECG suggestive of malign ventricular arrhythmia at visit 0
* Type 1 diabetes
* HbA1c \> 10% measured at visit 0
* Use of GLP-1 receptor agonists (Exenatide, Liraglutide or other) or glitazones, pramlintide or any DPP-IV inhibitor within 30 days prior to randomisation (visit 1)
* Known or suspected hypersensitivity to trial product or related products
* Alcohol/drug abuse
* Pregnant or nursing women
* Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives
* Cancer unless in complete remission for ≥5 years
* Liver disease with elevated plasma alanine aminotransferase (ALT) of more than three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
* Inflammatory bowel disease
* Acute or chronic pancreatitis
* Gastroparesis
* Compromised kidney function (eGFR \< 30 ml/min), dialysis or kidney transplantation
* History of thyroidea adenoma or carcinoma
* Severely elevated blood pressure (systolic \>180 mmHg and/or diastolic \>105 mmHg)
* Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation
* Simultaneous participation in any other clinical intervention trial
* Receipt of an investigational drug with 30 days prior to visit 0

Answer: C