An exploratory phase 2 study to asses the effect of Dapagliflozin on Glomerular Filtration Rate (GFR) in subjects with type 2 Diabetes who have inadequate glycemic and blood pressure (BP) control.

1) willing and able to give signed and dated written informed consent.
2) type 2 diabetes with inadequate glycemic control, defined as
central laboratory HbA1c >= 6.6% and <= 9.5% obtained at the enrollment visit.
3) metformin (XR or IR) and/or SU for at least 4 weeks prior to enrollment at any stable dose.
4). inadequate BP control, defined as seated SBP >= 130 and < 165 mmHg AND/OR seated DBP >= 80 and < 105 mmHg
5) C-peptide >= 0.8 ng/ml (0.27 nmol/L)
6) BMI <= 45.0 kg/m2 at the enrollment visit.
7) Men and women, ages >= 18 to <= 70 years.
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception

Main exclusion criteria:
1) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period.
2) Women who are pregnant or breastfeeding.
3) Women with a positive pregnancy test on enrollment or prior to investigational product administration and/or injection of iohexol, and, for subjects participating in the substudy, prior to administration of radioisotopes for determination of RCM and PV.
4) Estimated GFR (eGFR) by the Modification of Diet in Renal Disease (MDRD)
formula <= 60 mL/min/1.73m2 and >= 150 mL/min/1.73m2.
5) Urine albumin to creatinine ratio (UACR) >= 300 mg/g (33.9 mg/mmol/Cr).
6) Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN).
7) Alanine aminotransferase (ALT) > 3X ULN.
8) Serum Total Bilirubin > 2 mg/dL (34.2 µmol/L).
9) Serum Creatinine (Scr) >= 1.50 mg/dL (133 µmol/L) for men; SCr >= 1.40 mg/dL
(124 µmol/L) for women.
10) Hemoglobin <= 10.0 g/dL (100 g/L) for men; hemoglobin <= 9.0 g/dL (90 g/L) for women.
11) Creatine kinase (CK) > 3X ULN.
12) Positive for hepatitis B surface antigen.
13) Positive for anti-hepatitis C virus antibody.
14) Abnormal free T4 value.
15) History of diabetes insipidus.
16) Symptoms of poorly controlled diabetes that would preclude participation in this trial including, but not limited to, marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to enrollment, or other signs and symptoms.
17) History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
CV/Vascular Diseases: Any of the following CV/Vascular Diseases within 6 months
of the enrollment visit:
18) Myocardial infarction.
19) Cardiac surgery or revascularization (coronary artery bypass surgry [CABG]/
percutaneous transluminal coronary angioplasty [PTCA]).
20) Unstable angina.
21) Unstable congestive heart failure (CHF).
22) CHF New York Heart Association (NYHA) Class III or IV. (see Appendix 3)
23) Transient ischemic attack (TIA) or significant cerebrovascular disease.
24) Unstable or previously undiagnosed arrhythmia.
25) History of malignant or accelerated hypertension.
26) History of gout.
27) History of unstable or rapidly progressing renal disease.
28) Conditions of congenital renal glucosuria.
29) Significant hepatic disease, including but not limited to, chronic active hepatitis and/or severe hepatic insufficiency.
30) Documented history of hepatotoxicity with any medication.
31) Documented history of severe hepatobiliary disease.
32) History of hemoglobinopathy, with the exception of sickle cell trait (SA) or thalassemia minor; or chronic or recurrent hemolysis.
33) Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the
6 weeks prior to the enrollment visit.
34) Malignancy within 5 years of the enrollment visit (with the exception of treated basal cell or treated squamous cell carcinoma of the skin).
35) Known immunocompromised status, including but not limited to, individuals who have undergone organ transplantation or who are positive for the human immunodeficiency virus.
36) Allergies or contraindication to the contents of dapagliflozin tablets.
37) History of adverse reaction to radio-contrast dye.
38) Allergy or contraindication to use of thiazide diuretics.
39) Administration of insulin or any other antihyperglycemic therapy (other than metformin and/or SU), at any dose and time, during the 4 weeks prior to the enrollment visit.
40) Administration of any diuretics or other drugs approved for the treatment of hypertension (with the exception of either ACEI or ARB), at any dose and time, during the 12 weeks prior to the enrollment visit.
41) Administration of both ACEI and ARB.
42) Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for > 4 weeks within 3 months prior to enrollment visit.
43) Administration of sibutramine, phentermine, rimonabant, benzphetamine,
diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days of the
enrollment visit.
44) Any unstable endocrine, psychiatric, rheumatic disorders as judged by the
Investigator.
45) Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data.
46) Subject who, in the judgment of the Investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data.