Intervention: Dapagliflozin
Trial phase: Not Applicable
ATC code: A10BD15 | A10BD21 | A10BD25 | A10BK01
SMILES: CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 15
Group description: dapagliflozin 10mg (oral tablet) and exenatide (5µg acutely)/Exenatide extended release (long term) placebo (subcutaneous injection)

Dapagliflozin: Eighty (80) patients with T1D will be enrolled and randomized into 4 groups(20 each) to receive placebo, or dapagliflozin, or exenatide (5µg acutely)/Exenatide extended release (long term), or exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin treatments acutely and for 12 weeks
Eligibility criteria:
Inclusion Criteria:

Type 1 Diabetes for at least 1 year on continuous subcutaneous insulin infusion (CSII; also known as insulin pump)
HbA1c of 7-10% (inclusive)
Ages 18-65 years (inclusive of ages 18 and 65)
BMI 20-30 kg/m2

Exclusion Criteria:

Inability to give informed consent
Inability or refusal to comply with protocol
Use of GLP-1 Receptor Agonists in the last 3 months or DPP-IV and SGLT-2 inhibitors therapy in the last 1 month.
Risk for pancreatitis (e.g., history of gallstones, alcohol abuse, and hypertriglyceridemia)
History of pancreatitis and or chronic pancreatitis
Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) or stroke in the previous 3 months.
Congestive Heart Failure class III or IV or tachyarrhythmia.

Hepatic disease: Severe hepatic insufficiency and/or significant abnormal liver function defined as:

Aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
Total bilirubin >2.0 mg/dL (34.2 µmol/L)
Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
Liver function tests more than 3 times the upper limit of normal
Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or eGFR <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease.
History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.
HIV positive
History of gastroparesis
History of medullary thyroid carcinoma or MEN 2 syndrome
History of recurring UTI
Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia.
Prior history of a malignant disease requiring chemotherapy or patients with a prior history of bladder cancer regardless of treatment
Alcoholism or drug addiction.
Hypertriglyceridemia (>400 mg/dl).
Any other life-threatening, non-cardiac disease
Uncontrolled hypertension (BP > 160/95 mm of Hg)
Patients with hypotension or at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics or recently donated >500ml of blood should have careful monitoring of their volume status
Pregnant or breastfeeding patients or patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD)
Use of hormonal medications, 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
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)
Known hypersensitivity to heparin/ IV catheter equipment.
Eating disorders (anorexia, bulimia) or gastrointestinal disorders
Having a history of bariatric surgery
Debilitating psychiatric disorder such as psychosis or neurological condition that might confound outcome variables
Use of an investigational agent or therapeutic regimen within 30 days of study
Participation in any other concurrent clinical trial