Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adding Liraglutide to the Backbone Therapy of Biguanide in Patients With Coronary Artery Disease and Newly Diagnosed Type-2 Diabetes
Brief Summary: The purpose of this study is to investigate the effect of combined glucagon-like-peptide-1 (GLP-1) analogue and metformin therapy on glucose metabolic and cardiovascular endpoints compared to metformin monotherapy in patients with coronary artery disease (CAD) and newly diagnosed type 2 diabetes (T2D).

It is hypothesized that GLP-1 analogue added to backbone therapy of metformin in CAD patients with T2D will improve beta-cell function, left ventricular ejection fraction (LVEF), heart rate variability and lower 24h blood pressure among other selected endpoints.

The present study on CAD patients with newly diagnosed T2D will address these selected endpoints during an investigator initiated, randomized, double blind, crossover, placebo-controlled 12 + 12 weeks intervention study with a 2 week wash-out period.


Options:
A: Inclusion Criteria:

1. Stable CAD documented by one of the following:

   * Previous MI (a minimum of 6 weeks after an acute MI)
   * Previous coronary revascularization
   * CAD confirmed by an abnormal coronary angiography (CAG) or CT-angiography showing stenosis \> 50% of any major coronary arteries.
2. Body mass index (BMI) \>/= 25,0 kg/m2
3. Age \>/= 18 years and \</= 85 years
4. Type 2 diabetes diagnosed by one of the following criteria:

   * HbA1c \>/= 6.5%
   * HbA1c \< 6.5 % and fasting plasma glucose \>/= 7.0 mmol/l (confirmed)
   * HbA1c \< 6.5 % and a 2 h plasma glucose value during OGTT \>/= 11.1 mmol/l

The data for glucose metabolism are accepted provided that they have been obtained within 24 months prior to inclusion of the patient. The glucose metabolic categories are defined by ADA and WHO criteria.

Exclusion Criteria:

* Type 1 diabetes mellitus defined as C-peptide \< 450 pM
* Previously diagnosed diabetes mellitus for more than 24 months prior to the screening procedure for this trial, except from gestational diabetes
* Use of more than 2 types of oral antidiabetic medication and/or use of parenteral antidiabetic medication in the period of 3 months prior to the screening visit. It is accepted that the patient continues his usual antidiabetic medication after the screening visit but antidiabetic medication must be discontinued 2 weeks prior to the baseline visit.
* Significant heart disease (NYHA \> 2; Ejection Fraction \< 40% and unstable angina pectoris) and known severe valve disease
* Documented atrial fibrillation or atrial flutter within 6 weeks previous to the screening. Paroxysmal atrial fibrillation is accepted if sinus rhythm is achieved at the screening.
* Uncontrolled arterial hypertension (\> 180/100 mmHg) at the time of screening
* Liver (transaminases greater than x 2 the upper normal level) or renal diseases (eGFR \< 60 ml/min)
* Amylase greater than x 3 the upper reference value
* Any chronic medical condition to unduly increase risk for the potential enrollee as judged by study investigators
* Dysregulated myxedema or hyperthyroid condition defined by a value of TSH \< 0,1 and \> 10,0 milli U/L
* Anemia (\< 85% of lower normal limit), leucopenia (\< 85% of lower normal limit), or thrombocytopenia (\< 85% of lower normal limit)
* Pregnancy or failure to comply with contraception planning within two years, or breastfeeding
* Abuse of alcohol or drugs, or any other co-existing condition that would make patients unsuitable to participate in the study, as judged by the investigators
* Use of immunosuppressive therapy in the preceding 12 months
* Chronic pancreatitis or previous acute pancreatitis
* Known or suspected hypersensitivity to trial product(s) or related products
* Treatment with oral glucocorticoids, calcineurin inhibitors, or dipeptidyl peptidase 4 (DPP4) inhibitors, or other GLP-1 mimetics (e.g. exenatide), which in the Investigator's opinion could interfere with glucose metabolism
* Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, which in the Investigator's opinion could interfere with the results of the trail
* Inflammatory bowel disease
* Previous bowel resection
* Clinical signs of diabetic gastroparesis
* Plasma calcium-ion \>/= 1,45 mmol/L
* Plasma calcitonin \>/= 50 ng/L
* Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2
* Refusal to sign informed consent.
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:

* Type 2 diabetes treated with one or more oral agents
* Persistent fasting glucose \> 140 mg/dl or HbA1c \> 7%
* Stable and maximally effective doses of one or more oral agents for 3 months
* Presence of diabetic peripheral neuropathy
* Age between 18 and 70 years
* No risk factors or other causes of neuropathy
* Willingness and capacity to sign the Institutional Review Board approved consent form and cooperate with the medical procedures for study duration

Exclusion Criteria:

* Nursing mothers or pregnant women
* A history of previous kidney, pancreas or cardiac transplantation
* A past history of neuropathy (independent of diabetes) or with a disease known to be associated with neuropathy (e.g., hepatitis C, end stage renal disease, lupus)
* Amputation of any part of either lower extremity for any reason or traumatic loss of any part of either lower extremity or congenital absence or severe deformity of lower extremity
* HbA1c \> 10%
* Participation in an experimental medication trial within 3 months of starting the study.
* Undergoing therapy for malignant disease other than basal- or squamous cell carcinoma
* Requiring long-term glucocorticoid therapy
* Inability or unwillingness to comply with the protocol
D: 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

Answer: A