An Investigation Into the Effect of Dapagliflozin on Ketogenesis in Type 1 Diabetes

This is an interventional treatment trial for Evaluate Ketogenic Stress focused on measuring Dapagliflozin, Ketogenesis, Type 1 Diabetes, DKA, ketones, exenatide/Bydureon Read More

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:

  1. Aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
  2. Total bilirubin >2.0 mg/dL (34.2 µmol/L)
  3. Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
  4. 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