Inhibition of Urinary Angiotensinogen and the Reduction of Blood Pressure by SGLT2 Inhibition in Patients With Type 2 Diabetes

• Status: Completed
• Trial end date: 2020-08-01
• Target enrollment: 0
• Participant gender: All

Summary

To assess the effect of 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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tulane University; Tulane University School of Medicine
• Collaborator: AstraZeneca
• Treatments: Angiotensin II; Angiotensinogen; Dapagliflozin

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 AST and/or ALT >3x ULN

• Total bilirubin >2.0 mg/dL

• Positive serologic evidence of current infectious liver disease, including Hepatitis B viral antibody 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 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.