Purpose

The investigators propose to treat newly diagnosed, hyperfiltering T2DM patients with or without microalbuminuria with dapagliflozin or metformin for 4 months. The metformin-treated group will serve as controls for improved glycemic control, since the investigators have shown that insulin therapy to normalize A1c reduces hyperfiltration and kidney size in T1DM patients.

Category

IRB Number
20160262HU
NCT Number
NCT02911792
Open to Enrollment
Yes
Sponsor
The University of Texas Health Science Center at San Antonio -



Study Contact

Andrea Hansis-diarte
+1 (210) 617-5300
hansisdiarte@uthscsa.edu

Principal Investigator
Alberto Chavez-Velazquez

Alberto Chavez-Velazquez

alberto.chavez-velazquez@uhs-sa.com

Andrea Hansis-diarte
+1 (210) 617-5300
hansisdiarte@uthscsa.edu



Eligibility

Eligible Ages
Between 30 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

    • Newly diagnosed, drug naïve, hyperfiltering and normofiltration patients with type 2 diabetes mellitus (T2DM)
    • Hyperfiltration is defined by GFR >135 ml/min•1.73m2
    • Normofiltration by a GFR = 90-134 ml/min•1.73m2
    • BMI = 20-45 kg/m2
    • HbA1c = 7.5% to 12%
    • Willingness to participate in the 16 week study protocol
    • Hematocrit >34% --BP < 145/90 mmHg

Exclusion Criteria

    • > 300 mg/day albumin excretion
    • Ingestion of medications known to interfere with the renin-angiotensin system or renal function, including diuretic therapy
    • Hospitalization for unstable angina, history of recent macrovascular (MI/stroke/TIA/ACS) disease, coronary artery revascularization (within 2 months prior to enrollment)
    • Proliferative diabetic retinopathy
    • History of cancer or major organ system disease
    • New York Heart class II-IV heart failure Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3x ULN or total bilirubin > 2.0 mg/dL (34.2 µmo/L)
    • Treatment with steroids, beta blockers, alpha blockers, antiobesity drugs
    • Pregnant or nursing mothers
    • Premenopausal females who are not practicing acceptable contraceptive methods Participation in another trial with an investigational drug within 30 days Alcohol or drug abuse within the preceding 6 months
    • Any condition, psychiatric or medical, which in the opinion of the investigator would interfere with the successful completion of the study
    • Orthostatic hypotension (> 15/10 mmHg decrease upon standing for 3 minutes)
    • Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen, Hepatitis C virus antibody and HIV
    • Volume depleted patients
    • Estimated glomerular filtration rate <60 mL/min•1.73m2. 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

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Condition
  • Diabetes Mellitus, Type 2

    • Arm Groups

    ArmDescriptionIntervention
    Active Comparator

    Metformin

    		Subjects who Drug naïve we will give Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).Subject who are on metformin at time of randomization we will add Glipizide 5 mg( to be increased to 10 mg at Visit 5), Subject who are on Glipizide at time of randomization we will add Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).
  • Drug: Glipizide 5 MG

    Oral diabetes medicine that helps control blood sugar levels.

  • Drug: Metformin

    Oral diabetes medicine that helps control blood sugar levels.

    Other names:

    • Metformin-XR

    • Experimental

    Dapagliflozin

    		Subjects will be randomized to dapagliflozin, 5 mg/day. After 2 weeks (Visit 5), dapagliflozin will be increased to 10 mg/day, Subjects who are taking Metformin at time of randomization we will add Dapagliflozin to current metformin.
  • Drug: Dapagliflozin

    SGLT2 inhibitor

    Other names:

    • Farxiga

  • Drug: Metformin

    Oral diabetes medicine that helps control blood sugar levels.

    Other names:

    • Metformin-XR

    •