An Investigation Into The Anti-hypertensive And Potential Anti-inflammatory Actions Of Dapagliflozin

Phase 4

Completed

Brief Summary: This is a single center, prospective, randomized, placebo -controlled, parallel design and double blind study to evaluate oxidative stress, inflammation and hypertension markers and mediators before and after treatment with dapagliflozin.

Detailed Description: Two groups of 26 patients each (total 52 patients) with type 2 diabetes on oral agents will be included in the study. One group will be randomized to dapagliflozin (a dose of 5 mg daily will be titrated to 10 mg daily during the first week) while the other will be placebo. The patients will be treated for 12 weeks. Only half the patients (equal numbers in both groups) will be tested for the secondary endpoints related to postprandial and single dose induced changes. The primary endpoint of the study is to detect a significant difference in the percent change in fasting Nuclear factor-k B (NFκB) activation (DNA binding activity) in mononuclear cells (MNC) before and after dapagliflozin use (0 week vs. 12 weeks) as compared to placebo.

Recruitment & Eligibility

Inclusion Criteria

Age 20-80 years inclusive.
Type 2 diabetes
BMI ≥30 kg/m2
Subjects on statins, ACE inhibitors, ARBs, thiazolidinediones and -antioxidants will be allowed as long as they are on stable doses of these -compounds and the dosage in not changed during the course of study. -Patients will be evenly distributed between the 2 groups based on statins, -ARBs, TZDs and ACE inhibitors use.
HbA1c ≤ 8.0%

Exclusion Criteria

Use of GLP-1 agonists or DPP-IV or SGLT-2 inhibitors therapy in the last 3 -months.
Risk for pancreatitis, i.e., history of gallstones, alcohol abuse, and -hypertriglyceridemia.
Coronary event or procedure (myocardial infarction, unstable angina, coronary -artery bypass, surgery or coronary angioplasty) in the previous 3 months.
Hepatic disease: 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
Total bilirubin >2.0 mg/dL (34.2 µmol/L)
Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
(liver function tests more than 3 times the upper limit of normal)
Renal impairment (serum eGFR <60 ml/min)
Any other life-threatening, non-cardiac disease
Uncontrolled hypertension (BP > 160/100 mm of Hg)
Congestive Heart Failure class III or IV.
Use of an investigational agent or therapeutic regimen within 30 days of study
Participation in any other concurrent clinical trial
pregnant or breastfeeding patients
Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients will be treated for 12 weeks with placebo once daily
Dapagliflozin	dapagliflozin	10 mg daily for the 12 weeks

Primary Outcome Measures

Name	Time	Method
Difference in the Percent Change in Fasting Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells Activation (DNA Binding Activity) in Mononuclear Cells Before and After Dapagliflozin Use	12 weeks	nuclear factor kappa-light-chain-enhancer of activated B cells measurement through Transcription factor assay

Secondary Outcome Measures

Name	Time	Method
Changes in Expression of Inflammatory Mediators	12 weeks	Tumor necrosis factor alpha measurement in mononuclear through real time polymerase chain reaction