Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Chronic and Acute Postprandial Vascular Effects of Exenatide vs. Metformin in Abdominally Obese Patients With Impaired Glucose Tolerance
Brief Summary: The purpose of this study is to compare the effects of exenatide versus metformin on vascular health with chronic (3-month) therapy and during a 2-hour period following a meal in patients with pre-diabetes. It is predicted that exenatide will improve vascular health to a greater degree compared to metformin.


Options:
A: Inclusion Criteria:

* Greater than or equal to 18 years old
* Impaired glucose tolerance: 2-hr oral glucose tolerance test (OGTT) plasma glucose \>140 mg/dL OR impaired fasting glucose: fasting glucose \> or = 100 mg/dL OR elevated glycosylated hemoglobin: Hemoglobin A1c \> or = 5.7%
* Abdominal obesity: waist circumference \>102 cm (men) and \>88 cm (women)
* Stable cardiovascular medication regimen (or other medications known to affect endothelial function) at least 1 month prior to enrollment and throughout the study

Exclusion Criteria:

* Type 2 diabetes
* Current use of glycemic control medications within one month of randomization
* Fasting glucose \>126 mg/dL
* Current use of weight loss medication
* Previous weight loss surgery
* History of severe gastrointestinal disease
* Standard clinical contraindications to exenatide or metformin therapy
* Unstable angina
* Heart failure
* Stroke or coronary artery bypass graft within 3 months of screening
* Women who are currently pregnant or planning to become pregnant
* Breastfeeding women
* Clinically significant liver disease
* Creatinine \> 1.5 mg/dL
* Hepatic function greater than 3 times upper limit of normal
* Patients who are mentally incompetent and cannot sign a Patient Informed Consent
B: Inclusion Criteria:

* 18-65 yr old HIV infected men and women.
* Stable (at least the past 6 months) on combined antiretroviral therapy (cART).
* Stable immune (\> 300 CD4+ T-cells/µL) and virologic (\< 50 copies HIV RNA/mL) status.
* Insulin resistant/impaired glucose tolerance (fasting glucose 100-125mg/dL, or 2-hr glucose 140-200mg/dL or fasting HOMA-IR= 2.5-6.0).
* Waist circumference \> 102 cm (men), \> 88 cm (women).
* BMI \> 20 kg/m2.
* Fasting hypertriglyceridemia \> 150 mg/dL.
* Low HDL-cholesterol (\< 40 mg/dL in men or \< 50 mg/dL in women).
* Platelet count \> 30,000/mm3.
* Absolute neutrophil count \> 750/mm3.
* Transaminases \< 2.5x the upper limit of normal.
* Long-term non-progressors (not taking anti-HIV medications) are not eligible.

Exclusion Criteria:

* Diabetes (T2DM, IDDM or diabetic ketoacidosis) or taking any glucose-lowering medication (e.g., insulin, TZDs, metformin, sulfonylurea).
* Any agent that might artifactually alter glycemic control (e.g., glucocorticoids, megace, rhGH, GH-secretagogue, testosterone derivatives, creatine monohydrate, chromium picolinate, AA/protein supplements, medium- or long-chain fatty acids) during 6 months prior to or during enrollment.
* History of serious CV disease. NYHA Functional Class III or IV (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, stroke, resting hypertension \> 160/95 mmHg), irregular heart rhythm, resting ST-segment depression \> 1mm). Treatment with medications for CV condition (e.g., α- or ß-blockers). Some BP-lowering medications (Ca++channel blocker, diuretic, or ACE inhibitor) are permitted.
* Moderate to severe renal insufficiency. Serum creatinine \> 1.7 mg/dL (men) \> 1.5 mg/dL (women).
* Plan or anticipate a change in anti-HIV medications during the study.
* Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 6 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.
* Chronic hepatitis B (HBV-surface antigen positive). Active hepatitis C (detectable Hep C RNA).
* Positive urine drug test for opiates, methamphetamine, heroin, cocaine. Active substance abuse that the MD-scientist believes may compromise safety, compliance, interfere with study drug or data interpretation.
* Hematocrit \< 34% in men or \< 25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin \< 10 gm/dL with symptoms.
* Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If using birth control pills-must be stable on this medication for at least 6 months prior to enrollment.
* Active malignancy or treatment with chemotherapeutic agents or radiation therapy or any cytokine or anti-cytokine therapy during 6 months prior to enrollment.
* History of pancreatitis
* \> 10% unintentional weight loss during the 6 months prior to enrollment.
* Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded.
* Blinded investigational drugs for 3 months prior to enrollment that will not be unblinded before enrollment.
* Nausea, vomiting, diarrhea (\> 4 loose stools/day) that are unresponsive to treatment.
C: Inclusion Criteria:

1. Fasting plasma glucose ≥90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus laboratory-based HbA1c ≤8.0% if treatment naïve. There is no upper limit for the 2-hour glucose on OGTT. In those taking metformin laboratory-based HbA1c must be ≤7.5% if on metformin for \<3 months and ≤7.0% if on metformin for 3-6 months.
2. Age 10-19 years
3. Pubertal development Tanner stage \>1 as defined by breast stage \>1 in girls, and testes \>3 cc's in boys.
4. Body mass index (BMI) ≥85th percentile but ≤50 kg/m2
5. Self-reported diabetes \<6 months in duration
6. Treatment with metformin for \<6 months preceding screening

Exclusion Criteria:

1. Underlying disease likely to limit life span and/or increase risk of intervention or an underlying condition that is likely to limit ability to participate in outcomes assessment
2. An underlying disease that affects glucose metabolism other than type 2 diabetes mellitus
3. Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
4. Treatment with insulin for \>1 week preceding screening
5. Active infections
6. Renal disease (serum creatinine \>1.2 mg/dl) or serum potassium abnormality (\<3.4 or \>5.5 mmol/l)
7. Anemia (hemoglobin \<11 g/dl in girls, \<12 g/dl in boys) or known coagulopathy
8. Cardiovascular disease, including uncontrolled hypertension defined as average systolic or diastolic blood pressure \> 99 percentile for age or \>135/90, despite adequately prescribed antihypertensive medications. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.
9. History of conditions that may be precipitated or exacerbated by a study drug:

   1. Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
   2. Excessive alcohol intake
   3. Sub-optimally treated thyroid disease
10. Conditions or behaviors likely to affect the conduct of the RISE Study

    1. Participant and/or parents unable or unwilling to give informed consent
    2. Participant and/or parents unable to adequately communicate with clinic staff
    3. Another household member is a participant or staff member in RISE
    4. Current, recent or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes in RISE
    5. Weight loss of ≥5% of body weight in the past 3 months for any reason other than post-partum weight loss. Participants taking weight loss drugs or using preparations taken for intended weight loss are excluded.
    6. Likely to move away from participating clinics in next 2 years
    7. Current (or anticipated) pregnancy and lactation.
    8. A pregnancy that was completed less than 6 months prior to screening.
    9. Breast feeding within 6 months prior to screening.
    10. Women of childbearing potential who are unwilling to use adequate contraception
    11. Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
11. Additional conditions may serve as criteria for exclusion at the discretion of the local site.
D: Inclusion Criteria:

* Body Mass Index (BMI) of either 30 kg/m\^2 or more or BMI of less than 30 kg/m\^2 to 27 kg/m\^2 with presence of co-morbidities
* Stable body weight during the previous 3 months (less than 5 kg self-reported weight change)
* Previously undergone dietary weight loss and was not able to maintain reduced weight

Exclusion Criteria:

* Diagnosis of type 1 or type 2 diabetes
* Previous treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (including liraglutide or exenatide), within the last 3 months
* Visit 1 thryoid stimulating hormone (TSH) outside of the range of 0.4-6.0 mIU/L
* History of chronic pancreatitis or idiopathic acute pancreatitis
* Obesity induced by other endocrinologic disorders (e.g., Cushing Syndrome)
* Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial
* Current participation in an organized diet reduction program (or within the last 3 months)
* Currently using or have used within three months before this trial: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phenteremine, or metformin
* Previous surgical treatment for obesity (excluding liposuction if performed more than one year before trial entry)
* History of major depressive disorder or a PHQ-9 (Patient Health Questionnaire-9) score of more than 15 within the last 2 years or history of other severe psychiatric disorders or diagnosis of an eating disorder
* Subjects with a lifetime history of a suicide attempt or history of any suicidal behavior within the past month before entry into the trial

Answer: A