Effect of Dapagliflozin on Hepatic and Renal Glucose Metabolism Subjects

Effect of Dapagliflozin on Hepatic and Renal Glucose Metabolism Subjects (11038)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endogenous Glucose Production Measurement	Endogenous Glucose Production in NGT/T2DM subjects before and after dapagliflozin/Placebo administration from baseline to 240 minutes.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Glucose Production Measurement of Change	Renal Glucose Production in T2DM and NGT subjects before and after dapagliflozin/placebo administration from baseline to 240 minutes.	Baseline to 3 weeks

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Eugenio Cersosimo, MD,PhD, The University of Texas Health Science Center at San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: December 2, 2016
• First Posted (Estimated): December 5, 2016

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: HSC20160596H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No