Triple Therapy in T1DM

Inclusion Criteria:

1. Type 1 Diabetes for at least 1 year on staple use of continuous subcutaneous insulininfusion (CSII) or multiple daily (four or more) injections (MDI) of insulin forlast 3 months.

2. C-peptide <0.23 nM

3. Minimum dose of insulin in Units/kg at entry: 0.5 U/kg for MDI and 0.4 U/kg for CSII

4. Regularly measuring blood sugars four or more times daily.

5. HbA1c of >7.5%.

6. Well versed in CHO counting*

7. Age 18-70 years.

8. BMI ≥25 kg/m2.

Exclusion Criteria:

1. Type 1 diabetes for less than 12 months, type 2 diabetes, chronic pancreatitis, MODY

2. Previous use of any agent other than insulin for treatment of diabetes in the last 3months.

3. History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g.,emergency room visit and/or hospitalization) within 3 month prior to the screeningvisit

4. Frequent episodes of severe hypoglycemia as defined by more than one episoderequiring medical assistance, emergency care (paramedics or emergency room care),and/or glucagon therapy administered by a third-party individual within 1 monthprior to the screening visit

5. Symptoms of poorly controlled diabetes that would preclude participation in thistrial

6. Subjects on a commercial weight loss program with ongoing weight loss, or on anintensive exercise program

7. History of bariatric surgery or lap-band procedure within 12 months prior toscreening

8. History of Addison's disease or chronic adrenal insufficiency

9. History of diabetes insipidus

10. Hepatic disease or cirrhosis with Aspartate Aminotransferase (AST) > 3X Upper limitof normal (ULN) and/or Alanine aminotransferase (ALT) > 3X ULN

11. Serum Total Bilirubin > 2X ULN unless exclusively caused by Gilbert's Syndrome

12. Hemoglobin < 11.0 g/dL (110 g/L) for men; hemoglobin < 10.0 g/dL (100 g/L) forwomen.

13. Coronary event or procedure (myocardial infarction, unstable angina, coronary arterybypass, surgery or coronary angioplasty) in the previous 3 months or patients withcongestive heart failure.

14. ESRD on hemodialysis; and or e-GFR < 60 ml/min/1.73m2

15. HIV or Hepatitis B/C positive status

16. Any other life-threatening, noncardiac disease

17. History of pancreatitis

18. Women who are pregnant or women of childbearing potential who are not using adequatecontraception or who are breast feeding

19. Inability to give informed consent

20. History of gastroparesis

21. History of medullary thyroid carcinoma or MEN 2 syndrome

22. History of serious hypersensitivity reaction to these agents

23. Painful gallstones

24. Alcoholism

25. Hypertriglyceridemia (>500 mg/dl)

26. Recurrent genital mycotic infection.

27. Hypovolemic patients or with chronic renal insufficiency.

28. Patients with any malignancy except treated in situ malignancy and basal cellcarcinoma of the skin

29. Unexplained hematuria

30. Patients with a history of diabetic retinopathy

31. Use of an investigational agent or therapeutic regimen within 30 days of study

32. Participation in any other concurrent interventional clinical trial