An Investigation Into the Effect of Dapagliflozin on Ketogenesis in Type 1 Diabetes
Evaluate Ketogenic Stress
About this trial
This is an interventional treatment trial for Evaluate Ketogenic Stress focused on measuring Dapagliflozin, Ketogenesis, Type 1 Diabetes, DKA, ketones, exenatide/Bydureon
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
Sites / Locations
- ECMC Ambulatory Center, 3rd Floor
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Active Comparator
Placebo Comparator
Active Comparator
Dapagliflozin Arm:
Exenatide extended release Arm:
Placebo Arm:
Exenatide extended release & dapagliflozin Arm:
dapagliflozin 10mg (oral tablet) and exenatide (5µg acutely)/Exenatide extended release (long term) placebo (subcutaneous injection)
subcutaneous injection of Exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin placebo
dapagliflozin placebo (oral tablet) and exenatide (5µg acutely)/Exenatide extended release (long term) placebo (subcutaneous injection)
Exenatide (5µg acutely)/Exenatide extended release (long term) and dapagliflozin 10mg