Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Randomized, Comparator-Controlled Study in Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl Versus Glimepiride on the Rate of Progression of Atherosclerotic Disease as Measured by Carotid Intima-Media Thickness
Brief Summary: The primary purpose of this study is to compare the effects of pioglitazone, once daily (QD), versus glimepiride on the amount of thickening of the carotid artery.


Options:
A: Inclusion Criteria:

asymptomatic patients with uni- or bilateral carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dL despite ongoing lipid lowering therapy

Exclusion Criteria:

* age \<18 or ≥81 years old
* known intolerance to evolocumab
* ongoing or previous treatment with PCSK9i
* prior stroke or transient ischemic attack
* total carotid occlusion
* major active infection or major hematologic, renal, hepatic, or endocrine dysfunction
* malignancy with life expectancy below 24 months
* failure to sign informed consent
B: Inclusion Criteria:

* Diagnosis of Heterozygous Familial Hypercholesterolemia
* At least 18 years of age

Exclusion Criteria:

* Women who are pregnant or lactating, or planning to become pregnant.
* Subjects with a clinically indicated need for statin (HMG-CoA reductase inhibitor) therapy other than atorvastatin or other concomitant therapy with known lipid altering effects on LDL-C and HDL-C including fibrates and nicotinic acid (high doses)
* Subjects taking any drugs known to be associated with an increased risk of myositis in combination with HMG-CoA reductase inhibitors
* Subjects with any other medical condition or laboratory abnormality which could affect subject safety, preclude evaluationof response, or render unlikely that the subject would complete the study
C: Inclusion Criteria:

* Mean sitting sBP and dBP prior to randomization of 140-180/90-105 mmHg
* Increased cardiovascular risk, e.g.: a) documented or clinical signs of peripheral atherosclerotic disease stage IIa or lower; b) diabetes mellitus type 2; c) left ventricular hypertrophy on echo; d) current smoking; e) old myocardial infarction, stroke or TIA
* Intima-media thickness of the common carotid artery greater than or equal to 0.8 and less than or equal to 1.6 mm (measured ultrasonographically) or the plaque volume of the carotid bulb greater than or equal to 4 μl and less than or equal to 500 μl

Exclusion Criteria:

* Body mass index \> 30
* Any type of known secondary hypertension
* Electrocardiographic evidence of 2nd or 3rd degree atrioventricular block, atrial fibrillation, cardiac arrhythmia requiring therapy or bradycardia at rest (\< 50/min)
* Obstructive pulmonary disease
* Claudicatio intermittens
* History or clinical evidence of any significant gastrointestinal, respiratory, hematological, metabolic, immunological or any other underlying disease which in the opinion of the investigator would interfere with the patient's participation in the trial
* Hypersensitivity or contraindication to ARBs, Beta-Blockers, HCTZ or any cross allergy
* Pre-treatment with ARBs or ACE inhibitors within 6 months prior to screening
* Treatment with disallowed medication
* Pregnant or breastfeeding females or females of childbearing potential without adequate contraception
* History of alcohol and/or drug abuse
D: Inclusion Criteria

* Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to the time of randomization.
* Diagnosis of type 2 diabetes mellitus.
* Has received appropriate counseling on lifestyle modification for type 2 diabetes, including diet and exercise.
* Naïve to or not currently taking antidiabetic therapy, or is currently treated with monotherapy or combination antidiabetic therapy.
* Glycosylated hemoglobin greater than or equal to 6.0% and less than 9% at screening if taking antidiabetic medication or glycosylated hemoglobin greater than or equal to 6.5% and less than 10% at screening if naïve to or not taking antidiabetic medication.

Exclusion Criteria

* Type 1 diabetes mellitus.
* Taking more than 2 antidiabetic therapies at screening. For combination medications, each component is counted as 1 therapy.
* Symptomatic coronary artery disease, cerebrovascular disease, or peripheral vascular disease at the time of screening.
* Taking or have taken pioglitazone or other thiazolidinediones within 12 weeks of randomization or were discontinued from thiazolidinedione therapy due to lack of efficacy or clinical or laboratory signs of intolerance.
* Was discontinued from glimepiride or other sulfonylureas due to lack of efficacy or clinical or laboratory signs of intolerance.
* Participating in another investigational study or has participated in an investigational study within the past 30 days or is scheduled to participate in an investigational study during the time frame of this study.
* Women who are pregnant, intend to become pregnant during the course of the study, or are lactating.
* Men who have serum creatinine greater than or equal to 2.0 mg/dL (greater than or equal to 1.5 mg/dL if taking metformin) and women with serum creatinine greater than or equal to 1.8 mg/dL (greater than or equal to1.4 mg/dL if taking metformin).
* Unexplained microscopic hematuria of greater than plus 1 confirmed by repeat testing.
* History of drug abuse or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.
* Clinical cardiac failure as defined by New York Heart Association class III or IV, or known left ventricular dysfunction measured as left ventricular ejection fraction less than 40%, or by current use of diuretics or angiotensin converting enzyme inhibitors for the treatment of heart failure. Use of these agents for other therapeutic reasons is not an exclusion.
* Alanine transaminase level of greater than 2.5 times the upper limit of normal, active liver disease or jaundice.
* Weighs greater than 300 pounds or has a body mass index greater than 45 kg/m2 as calculated by weight (kg)/height (m)2 or weight (pounds)/height (inches)2 x 703.
* Has taken excluded medications.
* Known or suspected malignancy or recurrence of malignancy within the past 5 years, with the exception of basal cell carcinoma and Stage 1 squamous cell carcinoma of the skin.
* Any disease where, in the opinion of the investigator, survival is expected to be less than 18 months.
* Anticipated to undergo coronary bypass surgery or cardiac intervention during the course of the study.
* Has, in the opinion of the investigator, clinically significant valvular heart disease likely to require surgical repair or replacement during the course of the study.
* Has had uncontrolled hypertension (ie, sitting systolic blood pressure greater than160 mm Hg or sitting diastolic blood pressure greater than 100 mm Hg) at randomization.
* Men who have hemoglobin less than10.5 g/dL and women who have hemoglobin less than10.0 g/dL.
* Triglycerides greater than 500 mg/dL.
* Unwilling or unable to comply with the protocol or scheduled appointments.
* Unable to understand verbal and/or written English or any other language for which a certified translation of the informed consent is available.
* Known or suspected hypersensitivity to blood, blood products, or albumin.
* Subjects for whom it is not possible to obtain good quality images of the common carotid artery for technical reasons.
* Potentially clinically significant stenosis of the carotid artery as determined according to current guidelines by the physician assessing carotid intima-media thickness results. In these cases, the carotid intima-media thickness results should be reviewed by the investigator in consultation with the carotid intima-media thickness physician prior to determining whether the subject should be randomized.
* Has had bilateral endarterectomies, bilateral carotid stents, or radiation to the head or neck.
* Has received radiation therapy in the past year, who has had more than one computed tomography scan in the past year, or who is unable to raise one's arms above one's head while in a prone position.

Answer: D