RISE Adult

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)

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.