Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, 3-Arm Parallel-Group, 2-Year (104-Week), Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-28431754 Compared With Glimepiride in the Treatment of Subjects With Type 2 Diabetes Mellitus Not Optimally Controlled on Metformin Monotherapy
Brief Summary: The purpose of this study is to demonstrate the efficacy, safety, and tolerability of canagliflozin (JNJ-28431754) compared with glimepiride in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin.


Options:
A: Inclusion Criteria:

* Patients must have a diagnosis of type 2 diabetes
* Body mass index (BMI) \>=22 to \<=45 kg/m2, at screening
* Patients must be taking a stable dosage of metformin as monotherapy at screening
* Patients must have a HbA1c between \>=7% and \<=9.5% at Week 2
* Patients must have a fasting plasma glucose (FPG) \<=270 mg/dL (15 mmol/L) at Week -2

Exclusion Criteria:

* Patients having prior exposure or known contraindication or suspected hypersensitivity to JNJ-28431754, glimepiride, or metformin
* History of diabetic ketoacidosis or type 1 diabetes mellitus
* History of pancreas or beta-cell transplantation
* History of active proliferative diabetic retinopathy
* History of hereditary glucose-galactose malabsorption or primary renal glucosuria
* Renal disease requiring treatment with immunosuppressive therapy within the past 12 months before screening or a history of dialysis or renal transplant
* Taken thiazolidinedione therapy in the past 16 weeks before screening
B: Inclusion Criteria:

* type 2 diabetes
* BMI 20-45kg/m2 inclusive

Exclusion Criteria:

* females who are pregnant, lactating, or less than 6 weeks post-partum
* current symptomatic heart failure (NYHA Class II-IV)
C: 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.
D: Inclusion Criteria:

* Type 2 diabetes
* Treatment with oral anti-diabetic drugs for at least 3 months
* HbA1c: 7.5-10.0 % (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 to 45 kg/m2

Exclusion Criteria:

* Treatment with insulin within the last 3 months
* Treatment with any drug that could interfere with the glucose level
* Any serious medical condition
* Females who are pregnant, have intention of becoming pregnant or are breastfeeding

Answer: A