Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-blind Phase III Study to Evaluate the Efficacy of BI 1356 5 mg and 10 mg vs. Placebo for 12 Weeks and vs. Voglibose 0.6 mg for 26 Weeks in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control, Followed by an Extension Study to 52 Weeks to Evaluate Long-term Safety
Brief Summary: The objective of the current study is to investigate the efficacy, safety and tolerability of Linagliptin (BI 1356) (5 mg or 10 mg / once daily) compared to placebo given for 12 weeks and voglibose for 26 weeks as mono therapy in patients with type 2 diabetes mellitus with insufficient glycaemic control. Furthermore, long-term safety is evaluated with an extension treatment to 52 weeks.


Options:
A: Inclusion criteria:

1. Patients completing the entire treatment period of the preceding double-blind trial 1245.19, 1245.20 or 1245.23 with or without rescue therapy.
2. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice and local legislation.

Exclusion criteria:

1. Patient who meet one or more of the withdrawal criteria of the treatment period of the previous trial 1245.19, 1245.20 or 1245.23.
2. Indication of liver disease, defined by serum levels of either alanine aminotransferase , aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal as determined during last visit of preceding trial.
3. Impaired renal function defined as glomerular filtration rate\<30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) as determined during last visit of preceding trial.
4. Contraindications to sitagliptin, pioglitazone, metformin or sulfonylurea according to local label, which started during trial participation in 1245.19, 1245.20 or 1245.23
5. Pre-menopausal women (last menstruation \< or = 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 (if acceptable by local authorities), double barrier method and vasectomised partner.
6. 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.
7. Participation in another trial with an investigational drug within 30 days prior to informed consent (except 1245.19, 1245.20 and 1245.23).
8. Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial.
B: Inclusion criteria:

1. Japanese patients with a diagnosis of type 2 diabetes mellitus. Antidiabetic therapy has to be stable for at least 10 weeks before Visit 1.
2. Glycosylated haemoglobin A1 (HbA1c) 7.0 - 10.0% at Visit 3 (beginning of the 2-week placebo run-in phase)
3. Age: \>= 20 and \<= 80
4. Body Mass Index (BMI) \<= 40 kg/m2

Exclusion criteria:

1. Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months before Visit 1
2. Impaired hepatic function
3. History of severe allergy/hypersensitivity
4. Treatment with anti-diabetic, anti obesity drugs, etc 3 months before Visit 1
5. Fasting blood glucose \>240 mg/dl (=13.3 mmol/L) at Visits 2 or 3
C: Inclusion Criteria:

* Have T2DM based on a history and clinical impression that is consistent with the World Health Organization (WHO) Classification of Diabetes
* Have a Clinical Frailty Scale (CFS) score of 4 or above or Total Illness Burden Index (TIBI) score of 5 or above as assessed at screening
* Have an A1c \>7.3% and \<10.9% at study entry and are not achieving desired glycemic control as evidenced by A1c measurement at least 0.4% higher than individualized treatment target set at screening.
* Have been treated for at least 3 months prior to the study entry with any of the following treatment options:

  * Diet/exercise only (only if they have known contraindications to metformin treatment)
  * Any dose of sulfonylurea
  * Effective or maximally-tolerated doses of metformin, dipeptidyl-peptidase-4 (DPP-4) inhibitor, thiazolidinedione, or acarbose used in monotherapy or in dual combination. The following doses are considered to be effective:

    * at least 1500 mg of metformin per day
    * At least 30 mg of pioglitazone per day
    * At least 4 mg of rosiglitazone per day
    * At least 75 mg of acarbose per day
    * Any marketed dose of DPP-4 inhibitor

Exclusion Criteria:

* Are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
* Have participated, within the last 60 days in a clinical trial involving an investigational product other than the investigational product used in this study. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
* Have previously completed or withdrawn from this study. This exclusion criterion does not apply to participants who are rescreened prior to randomization
* At study entry, have contraindications to sulfonylurea, insulin, or GLP-1 RA
* Have a history of pancreatitis, a personal or family history of medullary thyroid carcinoma, or have Multiple Endocrine Neoplasia syndrome type 2
* Have taken any injectable glucose-lowering agent, miglitol, meglitinide, Sodium/Glucose cotransporter-2 inhibitor, or other antihyperglycemia treatment that is not listed in the fourth inclusion criterion for more than 10 days within 3 months prior to the study entry
* In the opinion of investigator should have an individualized A1c target set at 8% or higher
* Have a body mass index (BMI) greater than 45 kg/m\^2
* Have had more than 1 episode of severe hypoglycemia within 24 weeks prior to the study
* Have cardiac disease with functional status that is Class III or IV according to the New York Heart Association Cardiac Disease Classification
* Have an estimated glomerular filtration rate (eGFR) \<30 milliliter/minute/1.73 m\^2 (mL/min/1.73 m\^2) or advanced renal disease including history of renal transplantation or currently receiving renal dialysis
* Have obvious clinical signs or symptoms or laboratory evidence of liver disease (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \> 2.5 times the upper limit of the reference range)
* Receive current therapy for a malignancy, other than basal-cell or squamous-cell skin cancer
* Received systemic glucocorticoids within the 3 months prior to entry for more than 14 consecutive days
* Have any other condition that precludes the participant from following and completing the study
D: 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.

Answer: B