Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM

Inclusion Criteria

• BMI = 25-35 kg/m^2
• must be drug naïve and/or on a stable dose (more than 3 months) of metformin and/or sulfonylurea
• HbA1c >7.0% and 3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
• Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women or ≥1.5 mg/dl for men, or eGFR 400 mg/dl), uncontrolled increased LDL-C
• Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)
• 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
• Prior history of a malignant disease requiring chemotherapy, prior history of bladder cancer regardless treatment
• 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
• History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.
• Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions
• Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide)
• Use of , thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors stopped for at least 8 weeks.
• Eating disorders (anorexia, bulimia) or gastrointestinal disorders
• Suspected pregnancy (documented negative serum β-hCG test), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months
• Active history of illicit substance abuse or significant intake of alcohol
• Having a history of bariatric surgery
• Patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD)
• Debilitating uncontrolled psychiatric disorder such as psychosis or neurological condition that might confound outcome variables
• Inability or refusal to comply with protocol
• Current participation or participation in an experimental drug study in previous three months