Effect of Dapagliflozin on Hepatic and Renal Glucose Metabolism Subjects (11038)
Overview
- Phase
- Phase 4
- Intervention
- Dapagliflozin
- Conditions
- Diabetes Mellitus, Type 2
- Sponsor
- The University of Texas Health Science Center at San Antonio
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Endogenous Glucose Production Measurement
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
T2DM individuals on Dapagliflozin
Individuals with type 2 diabetes mellitus - dapagliflozin
Intervention: Dapagliflozin
T2DM individuals on Placebo
Individuals with type 2 diabetes mellitus on placebo
Intervention: Placebo
Normal Glucose Tolerance (NGT) on Dapagliflozin
Individuals with normal glucose tolerance - dapagliflozin
Intervention: Dapagliflozin
Normal Glucose Tolerance (NGT) Placebo
Individuals with normal glucose tolerance - on placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Endogenous Glucose Production Measurement
Time Frame: 3 weeks
Endogenous Glucose Production in NGT/T2DM subjects before and after dapagliflozin/Placebo administration from baseline to 240 minutes.
Secondary Outcomes
- Renal Glucose Production Measurement of Change(Baseline to 3 weeks)