Triple Therapy in T1DM

Prior treatment

• Previous use of any agent other than insulin for treatment of diabetes in the last 3 months.
• History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g., emergency room visit and/or hospitalization) within 3 month prior to the screening visit
• Frequent episodes of severe hypoglycemia as defined by more than one episode requiring medical assistance, emergency care (paramedics or emergency room care), and/or glucagon therapy administered by a third-party individual within 1 month prior to the screening visit
• History of bariatric surgery or lap-band procedure within 12 months prior to screening
• Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 3 months or patients with congestive heart failure.
• Use of an investigational agent or therapeutic regimen within 30 days of study
• Participation in any other concurrent interventional clinical trial

Other illness

• Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY
• Symptoms of poorly controlled diabetes that would preclude participation in this trial
• History of Addison's disease or chronic adrenal insufficiency
• History of diabetes insipidus
• HIV or Hepatitis B/C positive status
• Any other life-threatening, noncardiac disease
• History of pancreatitis
• History of gastroparesis
• History of medullary thyroid carcinoma or MEN 2 syndrome
• History of serious hypersensitivity reaction to these agents
• Recurrent genital mycotic infection.
• Hypovolemic patients or with chronic renal insufficiency.
• Patients with any malignancy except treated in situ malignancy and basal cell carcinoma of the skin
• Patients with a history of diabetic retinopathy

Lab values

• Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) \> 3X Upper limit of normal (ULN) and/or Alanine aminotransferase (ALT) \> 3X ULN
• Serum Total Bilirubin \> 2X ULN unless exclusively caused by Gilbert's Syndrome
• Hemoglobin \< 11.0 g/dL (110 g/L) for men; hemoglobin \< 10.0 g/dL (100 g/L) for women.
• ESRD on hemodialysis; and or e-GFR \< 60 ml/min/1.73m2
• Hypertriglyceridemia (\>500 mg/dl)

Other

• Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program
• Women who are pregnant or women of childbearing potential who are not using adequate contraception or who are breast feeding
• Inability to give informed consent
• Painful gallstones
• Alcoholism
• Unexplained hematuria

• Type 1 Diabetes for at least 1 year on staple use of continuous subcutaneous insulin infusion (CSII) or multiple daily (four or more) injections (MDI) of insulin for last 3 months.
• C-peptide \<0.23 nM
• Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII
• Regularly measuring blood sugars four or more times daily.
• HbA1c of \>7.5%.
• Well versed in CHO counting\*
• Age 18-70 years.
• BMI ≥25 kg/m2.