Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Randomized, Double-Blind, Active-Comparator-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Ertugliflozin (MK-8835/PF-04971729) Compared With the Addition of Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin
Brief Summary: This study will evaluate the efficacy and safety of the addition of ertugliflozin (MK-8835/PF-04971729) compared with the addition of glimepiride in participants with T2DM who have inadequate glycemic control on metformin. The primary hypothesis of this study is that after 52 weeks, the change from baseline in hemoglobin A1c (A1C) in participants treated with the addition of ertugliflozin 15 mg once daily is non-inferior compared with that in participants treated with the addition of glimepiride.


Options:
A: Inclusion criteria:

1. Signed and dated written Informed Consent (IC) by date of Visit 1a in accordance with Good Clinical Practice (GCP) and local legislation
2. Patients with a diagnosis of type 2 diabetes mellitus and treatment naive or previously treated with any oral hypoglycaemic agent; antidiabetic therapy has to be unchanged for ten weeks prior to informed consent.
3. Glycosylated haemoglobin A1 (HbA1c) 7.5-11% at Visit 2 (Start of Run-in).
4. Male and female patients aged \> or = 18 and \< or = to 80 years at Visit 1a (Screening).
5. Body Mass Index (BMI) \< or = 40 kg/m2 at Visit 1a (Screening)
6. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.

Exclusion criteria:

1. Myocardial infarction, stroke or Transient Isquemic Atack (TIA) within 6 months prior to Inform Consent (IC)
2. Impaired hepatic function, defined by serum levels of either Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) determined at Visit 1a.
3. Known hypersensitivity or allergy to the investigational product or its excipients and/or to hydrochloride of pioglitazone or its excipients
4. Treatment with Glucagon-like peptide-1 (GLP-1) analogue / agonist within 3 months prior to IC.
5. Treatment with insulin within 3 months prior to IC
6. Treatment with anti-obesity drugs 3 months prior to IC.
7. Alcohol abuse within the 3 months prior to IC that would interfere with trial participation or drug abuse.
8. Participation in another trial with an investigational drug within 2 months prior to IC.
9. Fasting blood glucose \> 240 mg/dl (=13.3 mmol/L) at screening (Visit 1).
10. Pre-menopausal women (last menstruation \< or =1 year prior to signing IC) 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 transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made.
11. Treatment with systemic steroids or change in the dosage of thyroid hormone within six weeks prior to IC
12. Heart failure New York Heart Asociation (NYHA) class I-IV, or history of heart failure.
13. Diabetic ketoacidosis within 6 months prior to IC.
14. Hemodialyzed patients due to limited experience with Thiazolidinediones (TZDs)
15. Any other clinical condition wich, in the opinion of the investigator, would not alow safe completion of the protocol and safe administration of BI1356 and pioglitazone.
B: Inclusion Criteria:

* Type 2 diabetes
* Treated with oral anti-diabetic (OAD) drugs for at least 3 months
* Treated with one or more OAD and in moderate to poor glycemic control
* Body Mass Index (BMI) less than or equal to 45.0 kg/m2

Exclusion Criteria:

* Treatment with insulin within the last three months prior to the trial except due to intercurrent illness, at the discretion of the Investigator
* Any serious medical condition
* Treatment with any drug that could interfere with glucose level
C: Inclusion Criteria:

* Diagnosis of T2DM in accordance to American Diabetes Association guidelines
* On metformin monotherapy or metformin in combination with a single allowable anti-hyperglycemic agent (AHA), DPP-4 inhibitors, meglitinides and AGIs are listed as allowable AHAs along with sulfonylureas prior to study participation.
* Body Mass Index (BMI) ≥18.0 kg/m\^2
* Male or female not of reproductive potential
* If a female of reproductive potential, agree to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug.

Exclusion Criteria:

* History or presence of type 1 diabetes mellitus or a history of ketoacidosis
* History of other specific types of diabetes (eg, genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant).
* A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor
* Use of the following prohibited therapeutic agents within 12 weeks of study participation: insulin, injectable anti-hyperglycemic agents, pioglitazone or rosiglitazone, another SGLT2 inhibitor, bromocriptine (Cycloset®), colesevelam (Welchol®), and any other non-approved anti-hyperglycemic therapy
* Known hypersensitivity or intolerance to metformin or glimepiride
* On a weight-loss program or medication or medication associated with weight changes and is not weight-stable (\>=5% change in body weight in the last 6 months)
* History of bariatric surgery less than 12 months prior to study participation
* History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation
* Active, obstructive uropathy or an indwelling urinary catheter
* A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
* Known history of Human Immunodeficiency Virus (HIV)
* Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
* A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C (assessed by medical history), primary biliary cirrhosis, or symptomatic gallbladder disease
* Any clinically significant malabsorption condition
* Being treated for hyperthyroidism, or on thyroid replacement therapy that has not been at a stable dose for at least 6 weeks prior to study participation
* Previous randomization in a study with ertugliflozin
* Participation in other studies involving investigational drug(s) within 30 days of study participation and/or during the pre-randomization period
* A surgical procedure within 6 weeks prior to study participation or planned major surgery during the trial
* A positive urine pregnancy test
* Pregnant or breast-feeding, or expecting to conceive during the trial, including 14 days following the last dose of study drug
* Undergoing hormonal therapy in preparation to donate eggs during the period of the trial, including 14 days following the last dose of study drug
* Consumption of more than 2 alcoholic drinks per day or engages in binge drinking
* Donation of blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
D: Inclusion Criteria:

* All patients must have a diagnosis of T2DM and be currently treated with metformin and sulphonylurea
* Patients in the study must have a HbA1c between \>=7 and \<=10.5% and a fasting plasma glucose (FPG) \<300 mg/dL (16.7 mmol/L)

Exclusion Criteria:

* History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
* or a severe hypoglycemic episode within 6 months before screening

Answer: C