Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
Intervention: Dapagliflozin; Exenatide; Placebo
Intervention description: 10mg; Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly); Placebo for Dapagliflozin
Intervention MeSH terms: Dapagliflozin; Exenatide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      In this study, the researchers hope to learn about SGLT2 inhibition on EGP (endogenous
      glucose production) and plasma glucose concentration in diabetic subjects. Researchers will
      examine diabetes and the role of increased plasma glucagon, decline in plasma insulin, and
      fall in plasma glucose concentration.
    

Eligibility criteria:

        Inclusion Criteria:

          1. BMI = 25-35 kg/m^2

          2. must be drug naïve and/or on a stable dose (more than 3 months) of metformin and/or
             sulfonylurea

          3. HbA1c >7.0% and <10.0%

          4. Other than diabetes, subjects must be in good general health as determined by physical
             exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis.

          5. Only subjects whose body weight has been stable (± 3 lbs) over the preceding three
             months and who do not participate in an excessively heavy exercise program will be
             included.

        Exclusion Criteria:

          1. Presence of significant systemic disease, heart problems including congestive heart
             failure, unstable angina or acute myocardial infarction, current infectious liver
             disease, acute stroke or transient ischemic attacks, history of pancreatitis,
             urosepsis and pyelonephritis, genital mycotic infections, or Type 1 diabetes mellitus

          2. Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic
             hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or
             significant abnormal liver function tests defined as aspartate aminotransferase (AST)
             >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN

          3. Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women or ≥1.5 mg/dl for
             men, or eGFR <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal
             disease or end stage renal disease.

          4. Uncontrolled thyroid disease , Cushing's syndrome, congenital adrenal hyperplasia or
             hyperprolactinemia

          5. Significantly elevated triglyceride levels (fasting triglyceride > 400 mg/dl),
             uncontrolled increased LDL-C

          6. Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)

          7. Use of anti-obesity drugs or weight loss medications (prescription or OTC) and
             medications known to exacerbate glucose tolerance (such as isotretinoin, , GnRH
             agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8
             weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha
             reductase inhibitors (finesteride, spironolactone, flutamide) stopped for at least 4
             weeks

          8. Prior history of a malignant disease requiring chemotherapy, prior history of bladder
             cancer regardless treatment

          9. Patients at risk for volume depletion due to co-existing conditions or concomitant
             medications, such as loop diuretics should have careful monitoring of their volume
             status

         10. History of unexplained microscopic or gross hematuria, or microscopic hematuria at
             visit 1, confirmed by a follow-up sample at next scheduled visit.

         11. Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g.
             anaphylaxis, angioedema, exfoliative skin conditions

         12. Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide,
             liraglutide)

         13. Use of , thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2
             inhibitors stopped for at least 8 weeks.

         14. Eating disorders (anorexia, bulimia) or gastrointestinal disorders

         15. Suspected pregnancy (documented negative serum β-hCG test), desiring pregnancy in next
             6 months, breastfeeding, or known pregnancy in last 2 months

         16. Active history of illicit substance abuse or significant intake of alcohol

         17. Having a history of bariatric surgery

         18. Patient not willing to use two barrier method contraception during study period
             (unless sterilized or have an IUD)

         19. Debilitating uncontrolled psychiatric disorder such as psychosis or neurological
             condition that might confound outcome variables

         20. Inability or refusal to comply with protocol

         21. Current participation or participation in an experimental drug study in previous three
             months