RISE Adult Medication Study

Inclusion criteria

• 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.
• Age 20-65 years
• Body mass index (BMI) ≥25 kg/m2 but ≤50 kg/m2
• Self-reported diabetes <1 year in duration
• Drug naïve (no prior to oral glucose lowering agent(s), insulin or other injectable glucose lowering agents)

Exclusion criteria

• 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
• An underlying disease that affects glucose metabolism other than type 2 diabetes
• Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
• Active infections
• 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)
• Anemia (hemoglobin <11 g/dl in women, <12 g/dl in men) or known coagulopathy
• Cardiovascular disease, including uncontrolled hypertension. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.
• History of conditions that may be precipitated or exacerbated by a study drug:

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

• Unable or unwilling to give informed consent
• Unable to adequately communicate with clinic staff
• Another household member is a participant or staff member in RISE
• Current, recent or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes in RISE
• 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.
• Likely to move away from participating clinics in next two years
• Women of childbearing potential who are unwilling to use adequate contraception
• Current (or anticipated) pregnancy and lactation.
• Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
• Additional conditions may serve as criteria for exclusion at the discretion of the local site.