Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety and Effect of Liraglutide in Patients With Type 2 Diabetes and Severe Renal Insufficiency
Brief Summary: Incretin-based therapy for the treatment of patients with type 2 diabetes mellitus (T2D) is new and fundamentally different from the classical treatments with oral antidiabetic agents and insulin. The novel and original aspect of this investigator-initiated study is the focus on treatment with an incretin-based agent (the GLP-1 analogue liraglutide) in T2D patients with severely reduced kidney function. At present there is virtually no knowledge of the physiology and clinical implications of the role of incretin hormones and incretin-based therapy in this group of diabetic patients.The aim of the study is to establish an evidence-based rationale for introducing a GLP-1 analogue to the limited armamentarium of antidiabetic drugs for patients with type T2D and severe renal insufficiency. The overall hypothesis is that patients with T2D and severe renal insufficiency will tolerate and benefit from treatment with the GLP-1 analogue liraglutide, hereby improving glycaemic control and reducing risk factors of cardiovascular disease


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:

1. Diagnosis of type 2 diabetes mellitus prior to informed consent
2. Male or female patients on diet and exercise regimen who are drug naive or pre treated with any background therapy. Antidiabetic therapy has to be unchanged for 12 weeks prior to randomization.
3. Glycosylated haemoglobin (HbA1c) of \>= 7.0% and \<=10% for patients on background therapy or HbA1c \>= 7.0% and \<= 9.0% for drug naive patients
4. Age \>= 18 years
5. Body Mass index \<= 45 at Visit 1
6. Signed and dated informed consent
7. High cardiovascular risk

Exclusion criteria:

1. Uncontrolled hyperglycaemia with a glucose level \>240 mg/dl (\>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day)
2. Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase ALT or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at screening and/or run in.
3. Planned cardiac surgery or angioplasty within 3 months
4. Impaired renal function, defined as Glomerular Filtration Rate \<30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) during screening or run in.
5. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
6. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia)
7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
8. Contraindications to background therapy according to the local label
9. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight
10. 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
11. 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, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method and vasectomised partner
12. 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
13. Participation in another trial with an investigational drug within 30 days prior to informed consent
14. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial
15. Acute coronary syndrome, stroke or TIA within 2 months prior to informed consent
C: Inclusion Criteria:

* Patients eligible for inclusion in COURAGE will comprise all but very high-risk subjects, and will include those with chronic angina pectoris (Canadian Cardiovascular Society \[CCS\] Class I-III), uncomplicated MI, cooled down ACS, and asymptomatic (or "silent") myocardial ischemia.
* Patients may have single- or multi-vessel coronary artery disease and may have had prior bypass graft surgery or PCI.

It is important to emphasize that as many types of CAD patients as possible--reflecting the spectrum of patients encountered in contemporary clinical practice--will be enrolled in COURAGE.

Exclusion Criteria:
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: D