Inhibition of Urinary Angiotensinogen and the Reduction of Blood Pressure by SGLT2 Inhibition in Patients With Type 2 Diabetes
Condition: Type 2 Diabetes; Hypertension
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin; Placebo
Intervention description: 5mg pill taken once daily; 5mg pill taken once daily- placebo of Dapagliflozin
Intervention MeSH terms: Dapagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: SGLT-2 inhibitor; urinary angiotensinogen

Summary:

      To assess the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on blood pressure
      and urinary angiotensinogen. This is a cross over study design, where 40 subjects will
      receive Dapagliflozin for 6 weeks followed by placebo for 6 weeks, or placebo for 6 weeks
      followed by Dapagliflozin for 6 weeks. In addition there will be an arm of 10 subjects who
      will receive sulfonylurea in an open label as a comparative to the cross over subjects to
      assess if the effect of Dapagliflozin may also be in part due to improved glycemic control.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes with hypertension and on RAAS blocking drugs OR

          -  Type 2 diabetes without hypertension and not on RAAS blocking drugs

          -  Hemoglobin A1c between 7% and 9% (inclusive)

          -  Estimated glomerular filtration rate (eGFR) ≥60 ml/min

          -  Capacity to understand and sign informed consent

        Exclusion Criteria:

          -  Severe hepatic insufficiency and/or significant abnormal liver function defined as
             aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3x upper limit
             of normal (ULN)

          -  Total bilirubin >2.0 mg/dL

          -  Positive serologic evidence of current infectious liver disease, including Hepatitis B
             viral antibody immunoglobulin M (IGM), Hepatitis B surface antigen, and Hepatitis C
             virus antibody

          -  Estimated glomerular filtration rate (eGFR) <60 ml/min

          -  Recent cardiovascular events with the last 2 months: acute coronary syndrome (ACS),
             hospitalization for unstable angina or acute myocardial infarction, acute stroke or
             transient ischemic attack (TIA), or post coronary artery revascularization

          -  Congestive Heart Failure defined as New York Heart Association (NYHA) class IV,
             unstable or acute congestive heart failure

          -  Pregnant or breastfeeding patients

          -  Patients who, in the judgement of the investigator, may be at risk for dehydration

          -  Blood pressure at enrollment: Systolic ≥165 mmHg and/or Diastolic ≥110 mmHg; At
             randomization: Systolic ≥160 mmHg and/or Diastolic ≥100 mmHg

          -  Use of SGLT-2 inhibitor class drugs is an exclusion for all patients. For patients in
             the sulfonylurea arm, use of sulfonylurea class drugs is an exclusion.