Effect of Dapagliflozin on Hepatic and Renal Glucose Metabolism Subjects

Purpose

Researchers hope to determine the organ (liver and/or kidney) responsible for the increase in endogenous glucose production (EGP) following the induction of glucosuria (when glucose is excreted in detectable amounts in the urine) with an SGLT2 inhibitor, dapagliflozin.

Condition

  • Diabetes Mellitus, Type 2

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • 25-35 kg/m^2 - Normal Glucose Tolerance subjects (24) - Type 2 Diabetic Subjects (24) - Diabetic subjects must be on a stable dose (more than 3 months) of monotherapy or combination therapy with metformin and/or a sulfonylurea - Diabetic subjects must have HbA1c <8.0% - Other than diabetes, subjects must be in good general health as determined by physical exam, medical history, blood chemistries, CBC (complete blood count), TSH (thyroid-stimulating hormone), T4 (thyroxine), EKG (electrocardiogram) and urinanalysis. - Only subjects whose body weight has been stable (± 3 lbs) over the preceding three months and who do not participate in an excessively heavy exercise program will be included.

Exclusion Criteria

  • Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea) will be excluded. - Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine >1.4 females or >1.5 males, or 24-hour urine albumin excretion > 300 mg will be excluded.

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
T2DM individuals on Dapagliflozin 		Individuals with type 2 diabetes mellitus - dapagliflozin
  • Drug: Dapagliflozin
    dapagliflozin, 10mg tablet
    Other names:
    • Farxiga
Placebo Comparator
T2DM individuals on Placebo 		Individuals with type 2 diabetes mellitus on placebo
  • Drug: Placebo
    Placebo for dapagliflozin
Active Comparator
Normal Glucose Tolerance (NGT) on Dapagliflozin 		Individuals with normal glucose tolerance - dapagliflozin
  • Drug: Dapagliflozin
    dapagliflozin, 10mg tablet
    Other names:
    • Farxiga
Placebo Comparator
Normal Glucose Tolerance (NGT) Placebo 		Individuals with normal glucose tolerance - on placebo
  • Drug: Placebo
    Placebo for dapagliflozin

More Details

Status
Completed
Sponsor
The University of Texas Health Science Center at San Antonio

Study Contact

Detailed Description

Researchers will measure the rate of hepatic and renal glucose production following dapagliflozin administration to determine the site of increase in EGP, liver versus kidney. Researchers will measure the rate of whole body glucose production with 3-3H-glucose (a form of radioactive glucose) and renal glucose production by renal vein catheterization in T2DM (type 2 diabetes mellitus) and in lean healthy NGT (normal glucose tolerance) individuals. Because the increase in EGP is associated with an increase in plasma glucagon concentration and renal glucose production is stated to be unresponsive to glucagon, the investigators anticipate that the liver will be responsible, in part, for the increase in EGP.