Please select the eligibility criteria that correspond to the clinical trial below.
Title: Liraglutide Effect and Action in Diabetes (LEAD-2): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Metformin Versus Metformin Monotherapy Versus Metformin and Glimepiride Combination Therapy in Subjects With Type 2 Diabetes
Brief Summary: This trial is conducted in Europe, Oceania, Africa, Asia and South America. This trial is designed to show the effect of treatment with liraglutide when adding to existing metformin therapy and to compare it with the effects of metformin monotherapy and combination therapy of metformin and glimepiride. Two trial periods: A 6 month (26 weeks) randomised, double-blinded period followed by an 18 months open-label extension, in total 2 years (104 weeks).


Options:
A: Inclusion Criteria:

* Age equal or above 35 years;
* Diagnosis of type 2 diabetes mellitus as defined by the American Diabetes Association , with at least one year of disease duration at the time of the screening visit;
* Blood glucose lowering treatment with Metformin alone (monotherapy) at a stable dose of at least 1.5 g/day (or maximum tolerated dose) in the 3 months prior to the screening visit;
* Insufficient metabolic control as defined by recent (last six months) HbA1c ≥ 7% in any peripheral laboratory and confirmed at the time of the screening;
* Absence of a recent clinically-relevant progression of micro- and macro-vascular complications (see exclusion criteria);
* Written informed consent to participate to the study.

Exclusion criteria:

* Age below 35 years
* Type 1 diabetes or other causes of diabetes (pancreatectomy, gestational diabetes, etc.)
* HbA1c \< 7% or ≥ 9% at the screening visit
* Treatment with any blood glucose lowering treatment other than Metformin in the six months before screening visit
* BMI \< 20 or ≥ 40 kg/m2, or current/ past history of clinically-relevant eating disorders (including -but no limited to- nervous anorexia, bulimia, binge-eating disorders, etc.)
* Significant progression of diabetic macro-angiopathy or cardiovascular disease in the six months prior to study visit
* Significant progression of diabetic micro-angiopathy in the six months prior to study visit
* Organ failure or other severe diseases limiting life expectancy;
* Beginning, in the three months before screening visit, of any kind of drug which can modify glycemic levels (beta-blockers, diuretics...), or acute disease (acute infection, urinary tract infection...) in three months before screening visit
* History of inflammatory/infective/autoimmune chronic disease
* History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, gastric surgery, inflammatory bowel disease;
* Any clinically significant abnormality identified on physical examination, laboratory tests, ECG or vital signs at screening that in the judgment of the investigator would preclude safe completion of the study;
* Uncontrolled or inadequately controlled hypertension at screening (Systolic Blood Pressure (SBP)\>190 or Diastolic Blood Pressure (DBP) \>100 mmHg)
* Ongoing pregnancy or absence of effective contraception in women with childbearing potential
* Contraindications to the maintenance of the background therapy (Metformin), including -but not limited to- chronic kidney failure or plasma creatinine concentrations \> 1.5 mg/dL, severe respiratory failure, etc.;
* Contraindications to the use of a Sulfonylurea;
* Contraindications to the use of a DPP-IV Inhibitor;
* Laboratory findings, or other disease conditions, at the screening visit that might interfere with study measurements:

  1. Hemoglobinopathy known to affect HbA1c assays;
  2. Known chronic liver diseases, including HBV (hepatitis B virus) and HCV (hepatitis C virus) infection;
  3. Liver makers (aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltransferase (GGT) , bilirubin) above 2 times the upper normal limit;
  4. Amylase and/or lipase above 2 times the upper normal limit;
* Chronic use of systemic and/or inhaled corticosteroids (only topical corticosteroids are allowed);
* History of low compliance, clinically-relevant psychiatric disorders or any current/ historical finding suggesting the patient as inappropriate to follow the study procedures.
B: Inclusion criteria:

* Diagnosis typ 2 diabetes mellitus
* Male and female on diet and exercise regimen, pre-treated with metformin 12 weeks prior to randomisation
* HbA1c equal or greater than 7.0% and less than or equal to 10% at visit 1
* 18 years or more
* BMI equal or less than 45Kg/m2

Exclusion criteria:

* Uncontrolled hyperglycemia defined as glucose more that 13.3 mmol/L after overnight fast during placebo run-in
* Any other antidiabetic drug within 12 weeks prior to randomisation except metformin
* Acute coronary syndrome (non-STEMI, STEMI unstable angina pectoris), stroke or transient ischemic attack within 12 weeks of informed consent
* Indication of liver disease
* Moderate to severe renal impairment
* Bariatric surgery within past 2 years
* Medical history of cancer or treatment for cancer within last 5 years
* Blood dyscrasias or any disorders causing haemolysis or unstable red blood cell
* Contraindications hypersensitivity to concomitant drugs
* Treatment with anti-obesity drugs
C: Inclusion Criteria:

* Subjects diagnosed with type 2 diabetes and treated with oral anti-diabetic drugs (OADs) for at least 3 months
* HbA1c: 7.0-11.0 % (both incl.) in subjects on OAD monotherapy. 7.0-10.0 % (both incl.) in subjects on OAD combination therapy
* Body Mass Index (BMI) less than or equal 40 kg/m2

Exclusion Criteria:

* Subjects treated with insulin within the last three months
* Subjects with any serious medical condition
* Females of child bearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant or not using adequate contraceptive methods
* Subjects using any drug (except for OADs), which in the Investigator's opinion could interfere with the glucose level (e.g. systemic corticosteroids)
D: Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone or with metformin and one other oral antidiabetic drug
2. Glycosylated haemoglobin (HbA1c) 6.0 - 9.0% at screening for patients treated with metformin and one other oral antidiabetic drug
3. HbA1c 6.5 - 10.0% at screening for patients treated with metformin alone
4. HbA1c 6.5 - 10.0% at beginning of the placebo run-in phase

Exclusion criteria:

1. Myocardial infarction, stroke or transient ischemic attack (TIA)
2. Impaired hepatic function
3. Renal failure or renal impairment
4. Treatment with rosiglitazone or pioglitazone within 6 months prior to screening
5. Treatment with insulin or glucagon-like peptide 1 (GLP-1) analogue/antagonists within 3 months prior to screening

Answer: C