Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Linagliptin on Endothelial Function and Global Arginine Bioavailability Ratio in Coronary Artery Disease Patients With Early Diabetes
Brief Summary: This study is planned to evaluate if linagliptin can improve endothelial function in patients with type 2 diabetes mellitus. In addition, the effect of linagliptin on arginine bioavailability ratios and postchallenge glycaemic control will be studied.


Options:
A: Inclusion Criteria:

* Age: 40 to 80 years
* Early diabetes (postchallenge diabetes (2h glucose \>200 mg/dl or type 2 diabetes treated with diet only or on a stable dose of metformin monotherapy)
* Coronary atherosclerosis (diagnosed via coronary angiography or coronary computer tomography)

Exclusion Criteria:

* Acute coronary syndrome or cerebrovascular event within the previous 4 weeks
* Body Mass Index (BMI) \> 35 kg/m2
* HbA1c \<6.0% (42 mmol/mol)
* Serum creatinine \> 2.5 mg/dl
* Aspartate Transaminase (AST)/Alanine Transaminase (ALT)\>3x upper limit of normal
* HbA1c \>9.0% (\>75 mmol/mol)
* Heart failure \> New York Heart Association (NYHA) class II
* Uncontrolled hypertension (blood pressure \> 165 / 100 mmHg)
* Treatment with orally administered steroids
* New onset statin or Angiotensin Converting Enzym- (ACE-) inhibitor within the previous 6 weeks
* Known Malignancy
* Pregnancy or breast feeding women.
B: 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.
C: Inclusion Criteria:

* Men or women at least 40 years old. Women must be post-menopausal or using a highly effective method for avoidance of pregnancy.
* Diagnosis of type 2 diabetes.
* Established cardiovascular disease with at least one of the following: coronary artery disease, cerebrovascular disease, or peripheral arterial disease.
* HbA1c \>7.0% (53 mmol/mol) (based on the most recent documented laboratory measurement within 6 months).
* Able and willing to provide informed consent.

Exclusion Criteria:

* Severely reduced kidney function: eGFR \<30 ml/min/1.73 m\^2 (based on the last measured and documented laboratory measurement within 6 months) or renal replacement therapy.
* Use of a GLP-1 receptor agonist at Screening.
* Severe gastroparesis
* History of pancreatitis or considered clinically at significant risk of developing pancreatitis during the course of the study.
* Personal or family history of medullary carcinoma of the thyroid or subject with multiple endocrine neoplasia type 2 (MEN-2). Personal history of pancreatic neuroendocrine tumours.
* Medical history which might limit the subject's ability to take trial treatments for the duration of the study or to otherwise complete the study.
* Breastfeeding, pregnancy, or planning a pregnancy during the course of the study. Note: a pregnancy test will be performed on all women of child bearing potential prior to study entry.
* Known allergy to any GLP-1 receptor agonist or excipients of albiglutide.
* Use of another investigational product within 30 days or according to local regulations, or currently enrolled in a study of an investigational device.
* Any other reason the investigator deems the subject to be unsuitable for the study.
D: Inclusion criteria:

1. Patients completing the entire treatment period of the preceding double-blind trial 1245.19, 1245.20 or 1245.23 with or without rescue therapy.
2. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice and local legislation.

Exclusion criteria:

1. Patient who meet one or more of the withdrawal criteria of the treatment period of the previous trial 1245.19, 1245.20 or 1245.23.
2. Indication of liver disease, defined by serum levels of either alanine aminotransferase , aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal as determined during last visit of preceding trial.
3. Impaired renal function defined as glomerular filtration rate\<30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) as determined during last visit of preceding trial.
4. Contraindications to sitagliptin, pioglitazone, metformin or sulfonylurea according to local label, which started during trial participation in 1245.19, 1245.20 or 1245.23
5. Pre-menopausal women (last menstruation \< or = 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, oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner.
6. Alcohol or drug 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.
7. Participation in another trial with an investigational drug within 30 days prior to informed consent (except 1245.19, 1245.20 and 1245.23).
8. Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial.

Answer: A