Please select the eligibility criteria that correspond to the clinical trial below.
Title: CARMELINA: A Multicenter, International, Randomized, Parallel Group, Double-blind, Placebo-controlled, Cardiovascular Safety and Renal Microvascular Outcome Study With Linagliptin, 5 mg Once Daily in Patients With Type 2 Diabetes Mellitus at High Vascular Risk
Brief Summary: The aim of the study is to investigate the longterm impact on cardiovascular morbidity, mortality and renal function of treatment with linagliptin in a selected population of patients with Type 2 diabetes mellitus (T2DM) and to compare outcomes against placebo, on a background of standard of care.


Options:
A: Participation as a volunteer in the Diabetes Prevention Program (DPP).
B: Inclusion criteria:

1. Documented diagnosis of T2DM before visit 1(screening).
2. Male or female patients who are drug-naïve or pre-treated with any antidiabetic background medication, excluding treatment with Glucagon-like Peptide 1 (GLP-1) receptor agonists, Dipeptidyl-peptidase 4 (DPP-4) inhibitors or Sodium Glucose Linked Transporter 2 (SGLT-2) inhibitors if =\> consecutive 7 days.
3. Stable antidiabetic background medication (unchanged daily dose) for at least 8 weeks prior to randomization. If insulin is part of the background therapy, the average daily insulin dose should not have changed by more than 10% within the 8 weeks prior to randomization compared with the daily insulin dose at randomization.
4. HbA1c of =\> 6.5% and \<= 10.0% at Visit 1 (screening)
5. Age =\> 18 years at Visit 1(screening). For Japan only: Age =\> 20 years at Visit 1
6. Body Mass Index (BMI) \<= 45 kg/m2 at Visit 1 (screening)
7. Signed and dated written informed consent by date of Visit 1(screening) in accordance with Good Clinical Practice (GCP) and local legislation prior to any study related procedure
8. High risk of cardiovascular (CV) events defined by: 1) albuminuria (micro or macro) and previous macrovascular disease and/or 2) impaired renal function with predefined Urine Albumin Creatinine Ratio (UACR)

Exclusion criteria:

1. Type 1 diabetes mellitus.
2. Treatment (=\> 7 consecutive days) with GLP-1 receptor agonists, other DPP-4 inhibitors or SGLT-2 inhibitors prior to informed consent. Note: This also includes clinical trials where these antidiabetic drugs have been provided to the patient.
3. Active liver disease or impaired hepatic function, defined by serum levels of either Alanine Transaminase (ALT) (SGPT), Aspartate transaminase (AST) (SGOT), or alkaline phosphatase (AP) =\> 3 x upper limit of normal (ULN) as determined at Visit 1.
4. Estimated Glomerular filtration Rate (eGFR) \<15 ml/min/1.73 m2 (severe renal impairment or End Stage Renal Disease (ESRD), Modification of Diet in Renal Disease (MDRD) formula), as determined during screening at Visit 1 and/or the need for maintenance dialysis.
5. Any previous (or planned within next 12 months) bariatric surgery (open or laparoscopic) or intervention (gastric sleeve).
6. Pre-planned coronary artery re-vascularisation (PCI, CABG) or any previous PCI and/or CABG \<= 2 months prior informed consent.
7. Known hypersensitivity or allergy to the investigational products or its excipients.
8. Any previous or current alcohol or drug abuse that would interfere with trial participation in the opinion of the investigator.
9. Participation in another trial with an investigational drug ongoing or within 2 months prior to visit 1 (screening).
10. Pre-menopausal women (last menstruation = 1 year prior to informed consent) who are nursing or pregnant, are of child-bearing potential and are not practicing an acceptable method of birth control (acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if allowed by local authorities), double barrier method and vasectomised partner) or do not plan to continue using acceptable method of birth control throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
11. Patients considered unreliable by the investigator concerning the requirements for follow up during the study and/or compliance with study drug administration, have a life expectancy less than 5 years for non-CV causes, or have cancer other than non-melanoma skin cancer within last 3 years, or has any other condition than mentioned which in the opinion of the investigator, would not allow safe participation in the study.
12. Acute coronary syndrome (ACS), diagnosed \<= 2 months prior to visit 1 (screening).
13. Stroke or Transient Ischemic Attack (TIA) \<= 3 months prior to visit 1 (screening).
C: Inclusion Criteria:

1. Provision of informed consent before any trial specific procedures.
2. Diagnosed with type 2 diabetes mellitus based on the current American Diabetes Association guidelines.
3. Aged \>18 and \<80 years
4. Body Mass Index ≥23
5. HbA1c 48-85mmol/mol (last known result within in the previous 6 months)
6. Blood pressure \<145/90mmHg. Office BP at screening visit will be used however if this is above the inclusion criteria then the 24 hour or 16 hour recording at screening visit will be used to confirm that in the opinion of the PI the BP is adequately controlled.
7. Echocardiographic left ventricular (LV) hypertrophy (defined as an LV mass index of \>115g/m2 for men and \>95g/m2 for women indexed to body surface area or \>48g/m2.7 or \>44g/m2.7 when indexed to height) within the previous 6 months.
8. Women of childbearing potential must agree to take precautions to avoid pregnancy throughout the trial and for 4 weeks after intake of the last dose.

Exclusion Criteria:

1. 1. Any condition that in the opinion of the investigator may render the participant unable to complete the trial including non CV disease (e.g. active malignancy).
2. Participants with type 1 diabetes mellitus
3. Participants who have previously had an episode of diabetic ketoacidosis.
4. Serum Potassium or Sodium results outwith the normal range
5. Diagnosis of clinical heart failure
6. History of human immunodeficiency virus
7. LV systolic dysfunction (LVEF \<45%) (last known result within in the previous 6 months)
8. eGFR \<45ml/min (last known result within in the previous month)
9. Known liver function tests \>3 times upper limit of normal (based on last measures and documented laboratory measurement in the previous 6 months)
10. Body weight \>150Kg (unable to fit into a MRI scanner)
11. Contraindications to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
12. Past or current treatment with any SGLT2 inhibitor
13. Allergy to any SGLT2 inhibitor or lactose or galactose intolerance
14. Current treatment with loop diuretic
15. Currently receiving long term (\>30 consecutive days) treatment with an oral steroid
16. Pregnant or breast feeding participants
17. Involvement in the planning and/or conduct of the trial (applies to Astra Zeneca or representative staff and/or staff at the trial site).
18. Participation in another interventional study (other than observational trials and registries) within 30 days before visit 1.
19. Individuals considered at risk for poor protocol or medication compliance.
D: Inclusion Criteria:

* Male and female subjects ≥40 and ≤ 80 years of age
* History of type 2 diabetes
* Haemoglobin A1C ≥6.5 and ≤10 % within 3 months of the Screening Visit
* Established cardiovascular disease, defined as previous myocardial infarction ≥ 6 months ago, or previous coronary revascularization ≥ 2 months ago
* Any background antihyperglycemic therapy (which has been stable for at least 2 months)
* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial
* Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

Exclusion Criteria:

* Female subjects who are pregnant, lactating or of child bearing potential, or pre-menopausal women. (Menopause will be determined by patient and physician history)
* Type 1 diabetes
* Subjects currently treated with SGLT2 inhibitors, Glucagon-like peptide-1 (GLP1) receptor agonist, or saxagliptin
* Frequent episodes (\>4/month) of moderate hypoglycaemia, as defined by the Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes
* Any episode of severe hypoglycaemia within the past 12 months, as also defined by the Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes
* Subjects in whom coronary revascularisation by either Percutaneous coronary intervention (PCI) or bypass surgery is being contemplated within 6 months, or who have undergone revascularisation in the prior 2 months
* Modification of Diet in Renal Disease (MDRD) Estimated Glomerular Filtration Rate (eGFR)\< 60 ml/min/1.73 m2 at screening
* Significant allergy or known intolerance to SGLT2 inhibitors or any ingredient in the formulations
* Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatologic disease, haematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease and psychiatric disease
* Any malignancy not considered cured (except basal cell carcinoma of the skin). A subject is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening
* Blood donation within 4 weeks prior to screening, or stated intention to donate blood or blood products during the period of the study or within one month following completion of the study
* Subjects who have participated in studies of an investigational drug or device within 30 days prior to the screening visit
* Conditions preventing safe MRI imaging such as the subject's weight exceeding 500 lbs; maximum body dimension from side-to-side exceeding 70 cm and from back to front of torso exceeding 50 cm or the presence of metallic fragments, clips or devices
* LVEF \<30% on the most recent assessment within 6 months
* New York Heart Association (NYHA) Class IV or recent hospitalization for decompensated Heart Failure (HF) (\<3 months)
* Unstable coronary syndromes
* Moderate or severe aortic stenosis
* Moderate or severe aortic regurgitation
* Moderate or severe mitral stenosis
* Moderate or severe mitral regurgitation

Answer: B