Effects of Dapagliflozin 10 mg on Insulin Resistance in Patients With Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
Intervention: Dapagliflozin; Placebo
Intervention description: Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks; Matching placebo to Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks
Intervention MeSH terms: Dapagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 55.0
Sex: All
Minimum age: 35 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus; Dapagliflozin; Placebo; Insulin resistance; Insulin sensitivity

Summary:

      This is an 8-week, single centre, randomized, parallel-group, double-blind,
      placebo-controlled Phase IV study to evaluate the effect of dapagliflozin on tissue specific
      insulin sensitivity in patients with Type 2 diabetes mellitus
    

Eligibility criteria:

        Main Inclusion Criteria:

          1. Provision of signed informed consent prior to any study specific procedures.

          2. Female or male aged 35 to 70 years inclusive with suitable veins for cannulation or
             repeated venipuncture

          3. Type 2 Diabetes mellitus defined as HbA1c of ≥ 6.5% and ≤ 10.5%.

          4. Stable (≥ 3 months) T2D treatment with metformin and/or metformin+dipeptidyl
             peptidase-4 inhibitors (DPP-IV)

          5. Body mass index (BMI) ≤ 40 kg/m2.

          6. Female subjects must be of non-childbearing potential, meeting at least one of the
             following criteria:

               1. Hysterectomized females

               2. Postmenopausal women, defined as women who have not had a menstrual period within
                  1 year

        Main Exclusion Criteria:

          1. Any condition that is contraindicated with MRI such as, but not limited to, having a
             pacemaker or claustrophobia.

          2. Volume depleted patients. 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.

          3. Recent Cardiovascular Events in a patient:

               -  Acute Coronary Syndrome (ACS) within 2 months prior to enrolment

               -  Hospitalization for unstable angina or acute myocardial infarction within 2
                  months prior to enrolment

               -  Acute Stroke or Transient Ischemic Attack (TIA) within two months prior to
                  enrolment

               -  Less than two months post coronary artery revascularization

          4. Congestive heart failure defined as New York Heart Association (NYHA) class IV,
             unstable or acute congestive heart failure.

          5. Blood pressure at enrolment: Systolic BP ≥165 mm Hg and/or diastolic BP ≥100 mm Hg

          6. Any clinically significant illness, medical or surgical procedure or trauma within 4
             weeks of the first administration of the investigational product.

          7. On insulin, GLP-1 or other oral antidiabetic drug treatment (metformin or both
             metformin and DPP-IV allowed) or using other medications known to affect glucose
             metabolism.

          8. Any clinically significant abnormalities in physical examination, Electrocardiography
             (ECG) or clinical chemistry results as judged by the investigator. The following
             specific exclusion criteria apply to the selected Clinical Chemistry results:

               1. Creatinine clearance <60mL/min (estimated with Cockroft-Gault formula).

               2. 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.

               3. Total bilirubin (TB) >2.0 mg/dL (34.2 µmol/L).

          9. Body weight loss greater than 5% within 3 months prior to Visit 1.

         10. Previous PET scan

         11. History of or presence of (as found at Visit 1) any clinically significant disease,
             disorder or condition which, in the opinion of the investigator, may either put the
             subject at risk because of participation in the study, or influence the results or the
             subject's ability to participate in the study.