Please select the eligibility criteria that correspond to the clinical trial below.
Title: Restoring Insulin Secretion Adult Medication Study
Brief Summary: The RISE Adult Medication Study is a 4-arm, 3-center, clinical trial of adults with prediabetes and early type 2 diabetes to address the hypothesis that aggressive glucose lowering will lead to recovery of beta-cell function that will be sustained after withdrawal of treatment. Adult participants (ages 20-65) will be randomized to one of the following treatment regimens: (1) blinded placebo, (2) blinded metformin alone, (3) early intensive insulin treatment with basal insulin glargine followed by open-label metformin, (4) the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide plus open-label metformin.

The primary clinical question RISE will address is: Are improvements in ß-cell function following 12 months of active treatment maintained for 3 months following the withdrawal of therapy? Secondary outcomes will assess durability of glucose tolerance following withdrawal of therapy, and whether biomarkers obtained in the fasting state predict parameters of ß-cell function, insulin sensitivity and glucose tolerance and the response to an intervention.


Options:
A: Inclusion Criteria:

1. Prior completion of at least two months in a diet, exercise and lifestyle intervention program within the past two years
2. Fasting plasma glucose \>90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus HbA1C ≤7.0%. There is no lower limit for the A1C and no upper limit for the OGTT 2-hour glucose based on prior studies that allow us to identify people with falling β-cell function
3. Age 22-65 years
4. Body mass index (BMI) 30-40 kg/m2
5. For participants with diabetes, known duration \<1 year
6. No history of use of antidiabetic medications except during pregnancy

Exclusion Criteria:

1. Contraindications to LapBand(see Appendix 1)
2. Contraindication to MRI (claustrophobia; permanent metal objects such as pacemakers, prostheses, aneurysm clips)
3. Underlying disease(s) likely to (a) limit life span to less than study duration and/or (b) increase risk of intervention outside of the study and/or (c) limit ability to participate in outcomes assessment and/or (d) limit participation
4. An underlying disease known to have important effects on glucose metabolism
5. Active infections
6. Renal disease (serum creatinine ≥1.4 mg/dl for men; ≥1.3 mg/dl for women) or serum potassium abnormality (\<3.4 or \>5.5 mmol/l)
7. Anemia (hemoglobin \<11g/dl in women, \<12 g/dl in men) or known coagulopathy
8. Cardiovascular disease, including uncontrolled hypertension and symptomatic congestive heart failure. Participants must be able to safely tolerate administration of fluid/volume challenges during clamp studies.
9. Serum AST \>3 times upper limit of normal in local clinical lab
10. Excessive alcohol intake
11. Suboptimally treated thyroid disease
12. Conditions or behaviors likely to affect the conduct of the study

    1. unable or unwilling to give informed consent
    2. unable to adequately communicate with clinic staff
    3. another household member is a participant or staff member
    4. current or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes
    5. likely to move away from participating clinic in next 2 years
    6. current (or anticipated) pregnancy and lactation.
    7. major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of the study
    8. weight loss \>5% in past three months for any reason except postpartum weight loss.
13. additional conditions may serve as criteria for exclusion at the discretion of the local site
B: Inclusion Criteria:

* Informed consent
* Body mass index equal to or above 30 kg/m\^2
* Stable body weight (less than 5% self-reported change during the previous 3 months)
* Diagnosis of moderate or severe obstructive sleep apnoea (OSA)
* Unwilling or unable to use continuous positive airway pressure (CPAP) (or other positive airway pressure) treatment. No CPAP (or other positive airway pressure) treatment for at least four weeks prior to screening
* Ability and willingness to comply with all protocol procedures e.g. correct handling of trial product, compliance to visit schedule and dietary advice and complete trial related questionnaires

Exclusion Criteria:

* Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 inhibitors or insulin within the last 3 months prior to screening
* Diagnosis of type 1 or type 2 diabetes per judgement of the investigator
* Glycosylated haemoglobin (HbA1c) equal to or above 6.5%
* Significant craniofacial abnormalities that may cause OSA
* Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator
* Use of central stimulants, hypnotics, mirtazepine, opioids, trazodone within the previous 3 months prior to screening
* Obesity induced by drug treatment
* Treatment with pramlintide, sibutramine, orlistat, zonisamide, topiramate or phenteremine within the last 3 month prior to screening
* Previous surgical treatment for obesity
* Screening calcitonin equal to or above 50 ng/L
* Familial or personal history of Multiple Endocrine Neoplasia type 2 or familial Medullary Thyroid Carcinoma
* Personal history of non-familial Medullary Thyroid Carcinoma
* History of chronic pancreatitis or idiopathic acute pancreatitis
* History of Major Depressive Disorder or suicide attempts
* Systolic blood pressure equal to or above 160 mmHg and/or diastolic blood pressure equal to or above 100 mmHg
C: Inclusion Criteria:

* Blood glucose criteria must be met
* Body mass index (BMI) in the range 23-45

Exclusion Criteria:

* Diagnosis of diabetes
* Serious cardiovascular events within the past 6 months
* Use of insulin or any oral antidiabetic agent
* Other protocol-defined exclusion criteria may apply
D: Inclusion Criteria:

1. Fasting plasma glucose 95-125 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus HbA1c ≤7.0%. There is no upper limit for the 2-hour glucose on OGTT.
2. Age 20-65 years
3. Body mass index (BMI) ≥25 kg/m2 but ≤50 kg/m2
4. Self-reported diabetes \<1 year in duration
5. Drug naïve (no prior to oral glucose lowering agent(s), insulin or other injectable glucose lowering agents)

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
3. Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
4. Active infections
5. Renal disease (serum creatinine \>1.4 mg/dl for men; \>1.3 mg/dl for women) or serum potassium abnormality (\<3.4 or \>5.5 mmol/l)
6. Anemia (hemoglobin \<11 g/dl in women, \<12 g/dl in men) or known coagulopathy
7. Cardiovascular disease, including uncontrolled hypertension. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.
8. History of conditions that may be precipitated or exacerbated by a study drug:

   1. Pancreatitis
   2. Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
   3. Excessive alcohol intake
   4. Suboptimally treated thyroid disease
   5. Medullary carcinoma of the thyroid or MEN-2 (in participant or a family history)
   6. Hypertriglyceridemia (\>400 mg/dl despite treatment)
9. Conditions or behaviors likely to affect the conduct of the RISE Study

   1. Unable or unwilling to give informed consent
   2. 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% in past three 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 two years
   7. Women of childbearing potential who are unwilling to use adequate contraception
   8. Current (or anticipated) pregnancy and lactation.
   9. Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
10. Additional conditions may serve as criteria for exclusion at the discretion of the local site.

Answer: D