Please select the eligibility criteria that correspond to the clinical trial below.
Title: CSP #465 - Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)
Brief Summary: This study is a prospective, 2-arm, randomized controlled trial to determine whether glycemic control, achieved through intensification of treatment, is effective in preventing clinical macrovascular complications in patients with type 2 DM who are no longer responsive to oral agents alone. The study consists of a two-year accrual period and five years of follow-up (7 years total) of 1700 patients across 20 centers. We have powered the study to detect a 21% reduction in the primary event rate. Additional study goals are to determine whether the expenditures, discomfort, and adverse effects associated with intensive intervention are justified in terms of their clinical benefits, considering both macrovascular and microvascular complications.


Options:
A: Inclusion Criteria:

1. Must give written informed consent before participation. Patient information and consent form must be approved by the Danish Medicines Agency and the Regional Scientific Ethical Committee
2. Male or female patients \>18 years with type 2 diabetes (WHO criteria).
3. HbA1c ≥ 48 mmol/mol (6.5 %)
4. eGFR ≥ 30 ml/min/1.73 m2 (estimated by MDRD formula)
5. Fertile female patients must use chemical, hormonal or mechanical contraceptives or be in menopause (i.e. must not have had regular menstrual bleeding for at least one year) or have undergone bilateral oophorectomi or have been surgically sterilized or hysterectomised at least six months prior to screening
6. Patients must be on stable RAAS-blocking treatment (unchanged dose 4 weeks before inclusion)
7. Geometic mean urine albumin-to-creatinine ratio (UACR) above 30 mg/g at screening (measured in at least two of three consecutive morning spot urine samples)
8. Systolic blood pressure (SBP) must be lower than 180 mm Hg at screening.
9. Patients must be on stable glucose lowering medication for at least two weeks before the first visit.
10. Must be able to communicate with the investigator.

Exclusion Criteria:

1. SBP \> 180 mm Hg at screening
2. Type 1 diabetes mellitus
3. Chronic pancreatitis / previous acute pancreatitis
4. Known or suspected hypersensitivity to trial product(s) or related products.
5. Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon like peptide-1 agonists and sodium-glucose co-transporter 2 (SGLT-2) inhibitors, which in the investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening
6. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial
7. Inflammatory bowel disease
8. Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months
9. Previous bowel resection
10. Body mass index \<18.5 kg/m2
11. Females of childbearing potential who are pregnant, breast-feeding, intending to become pregnant or not using adequate contraceptive methods
12. Clinical signs of diabetic gastroparesis
13. Impaired liver function (transaminases \> two times upper reference levels)
14. The receipt of any investigational product 90 days prior to this trial
15. Known or suspected abuse of alcohol or narcotics
16. Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2
B: Inclusion Criteria:

* Patients with type 2 DM who are no longer responsive to maximum dose of one or more oral agents.

Exclusion Criteria:

* Angina pectoris, Canadian Class I-II,
* congestive heart failure, Class III-IV,
* stroke, incapacitating or in last 6 months,
* Myocardial infarction (MI) or invasive cardiovascular procedure within the past six months,
* ongoing diabetic gangrene,
* BMI \> 40,
* hemoglobinopathy that interferes with A1c monitoring,
* serum creatinine \> 1.6 mg/dL,
* fasting C-peptide \< 0.21 pmol/ml,
* Alanine Amino Transaminase (ALT) \> 3 times normal or serum bilirubin \> 1.9 mg/dL,
* malignancy or noncardiac life-threatening diseases making life expectancy \< 5 years,
* autonomic neuropathy,
* symptomatic pancreatic insufficiency (endocrine or exocrine),
* recurrent seizures within the past year,
* hypopituitarism,
* pregnancy, lactation, or planning a pregnancy,
* active psychosis or substance abuse,
* lack of access to a person who can assist or be called in an emergency,
* underlying conditions that in the site PI's judgment may prevent adherence to protocol,
* current participation in another clinical trial
C: Inclusion Criteria:

* Diagnosis of Type 2 diabetes mellitus
* Coronary arteriogram showing one or more vessels amenable to revascularization (greater than or equal to 50% stenosis)
* Objective documentation of ischemia OR subjectively documented typical angina with greater than or equal to 70% stenosis in at least one artery
* Suitability for coronary revascularization by at least one of the available methods (does not require the ability to achieve complete revascularization)
* Ability to perform all tasks related to glycemic control and risk factor management

Exclusion Criteria:

* Definite need for invasive intervention as determined by the attending cardiologist
* Prior bypass surgery (CABG) or prior catheter-based intervention within the 12 months before study entry
* Planned intervention for disease in bypass graft(s) if the patient is randomly assigned to a strategy of initial revascularization
* Class III or IV CHF
* Creatinine greater than 2.0 mg/dL
* HbA1c greater than 13%
* Need for major vascular surgery concomitant with revascularization (e.g., carotid endarterectomy)
* Left main stenosis greater than or equal to 50%
* Non-cardiac illness expected to limit survival
* Hepatic disease (ALT greater than 2 times the ULN)
* Fasting triglycerides greater than 1000 mg/dL in the presence of moderate glycemic control (HbA1c less than 9.0%)
* Current alcohol abuse
* Chronic steroid use judged to interfere with the control of diabetes, exceeding 10 mg of Prednisone per day or the equivalent
* Pregnancy, known, suspected, or planned in 5 years after study entry
* Geographically inaccessible or unable to return for follow-up
* Enrolled in a competing randomized trial or clinical study
* Unable to understand or cooperate with protocol requirements

Patients with Type 2 diabetes mellitus and CAD documented by coronary arteriography will be eligible for the trial if revascularization is not required for prompt control of severe or unstable angina. Diabetic patients who are being treated with insulin or oral hypoglycemic drugs will be eligible as well as diabetic patients treated with diet and exercise alone provided that a diagnosis of diabetes can be confirmed by record review or that a fasting plasma glucose (FPG) greater than 125/mg/dL (7.0 mmol/L) can be obtained. The determination of suitability for BARI 2D will be made by a physician-investigator at each participating institution on clinical grounds at the time of coronary angiography.

Significant CAD will be defined as at least one stenosis greater than 50%. Angina and ischemia will be assessed by use of patient self-report, physician examination, and appropriate diagnostic measures including exercise myocardial perfusion imaging, exercise echocardiography, exercise electrocardiography, and IV dipyridamole or adenosine myocardial perfusion imaging or invasively by doppler or pressure wire. Objective documentation of myocardial ischemia includes any of the following:

1. Exercise or pharmacologically-induced:

   1. Greater than or equal to 1 mm of horizontal or downsloping ST depression or elevation for greater than or equal to 60-80 milliseconds after the end of the QRS complex
   2. Myocardial perfusion defect
   3. Myocardial wall motion abnormality
2. Stabilized, prior acute coronary syndrome with CK-MB or troponin elevation or with new, greater than or equal to 0.5 mm ST depression or elevation, or T wave inversion of greater than or equal to 3 mm in 2 contiguous ECG leads
3. Doppler or pressure wire showing coronary flow reserve (CFR) less than 2.0 or fractional flow reserve (FFR) less than 0.75

Among patients without documented ischemia, only patients with stenosis greater than or equal to 70% presenting with classic anginal symptoms will be eligible for randomization.
D: Inclusion criteria - patients with T2D in dialysis

* Male or female; aged 18-85 years
* End-stage renal disease
* Chronic dialysis treatment (minimum 3 months)
* T2D (diagnosed according to WHO criteria)
* Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones) and/or insulin
* Documented beta cell function (evaluated by a glucagon test)

Inclusion criteria - patients with T2D and normal kidney function

* Male or female; aged 18-85 years
* Normal kidney function: Plasma creatinine \<0.105 mmol/L for men and \<0.090 mmol/L for women
* T2D (diagnosed according to WHO criteria)
* Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones) and/or insulin
* Documented beta cell function (evaluated by a glucagon test)
* Hemoglobin A1c ≥6.5%

Exclusion Criteria - both groups

* Type 1 diabetes mellitus
* Chronic pancreatitis / previous acute pancreatitis
* Known or suspected hypersensitivity to trial product(s) or related products
* Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors or other drugs, which in the Investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening
* Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder which in the investigators' opinion could interfere with the results of the trial
* Inflammatory bowel disease
* Cardiac disease defined as: decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months
* Body mass index ≤ 18.5 kg/m2 or ≥ 50.0 kg/m2
* Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
* Clinical signs of diabetic gastroparesis
* Impaired liver function (transaminases \>two times upper reference levels)
* Receipt of any investigational product 90 days prior to this trial
* Known or suspected abuse of alcohol or narcotics
* Screening calcitonin ≥50 ng/l
* Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

Answer: B