RISE Pediatric Medication Study

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.