Overview

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

Status:
Unknown status
Trial end date:
2018-10-01
Target enrollment:
0
Participant gender:
All
Summary
The study investigations include evaluation of the acute effects of a single dose of dapagliflozin (10mg), exenatide (5µg), a combination of exenatide and dapagliflozin or placebo under insulinopenic condition and the long term effect under basal conditions before and after 12 weeks treatment with dapagliflozin, Exenatide extended release, a combination of Exenatide extended release and dapagliflozin or placebo on ketogenesis, glucagon and lipolysis.
Phase:
Phase 4
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University at Buffalo
Collaborator:
AstraZeneca
Treatments:
Dapagliflozin
Exenatide
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:

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