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Effect of Dapagliflozin on Hepatic and Renal Glucose Metabolism Subjects

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

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02981966
Enrollment
32
Registered
2016-12-05
Start date
2019-05-23
Completion date
2023-05-31
Last updated
2024-03-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

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.

Interventions

DRUGDapagliflozin

dapagliflozin, 10mg tablet

DRUGPlacebo

Placebo for dapagliflozin

Sponsors

AstraZeneca
CollaboratorINDUSTRY
The University of Texas Health Science Center at San Antonio
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 70 Years
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.

Design outcomes

Primary

MeasureTime frameDescription
Endogenous Glucose Production Measurement3 weeksEndogenous Glucose Production in NGT/T2DM subjects before and after dapagliflozin/Placebo administration from baseline to 240 minutes.

Secondary

MeasureTime frameDescription
Renal Glucose Production Measurement of ChangeBaseline to 3 weeksRenal Glucose Production in T2DM and NGT subjects before and after dapagliflozin/placebo administration from baseline to 240 minutes.

Countries

United States

Participant flow

Participants by arm

ArmCount
T2DM Individuals on Dapagliflozin
Individuals with type 2 diabetes mellitus - dapagliflozin Dapagliflozin: dapagliflozin, 10mg tablet
13
T2DM Individuals on Placebo
Individuals with type 2 diabetes mellitus on placebo Placebo: Placebo for dapagliflozin
7
Normal Glucose Tolerance (NGT) on Dapagliflozin
Individuals with normal glucose tolerance - dapagliflozin Dapagliflozin: dapagliflozin, 10mg tablet
8
Normal Glucose Tolerance (NGT) Placebo
Individuals with normal glucose tolerance - on placebo Placebo: Placebo for dapagliflozin
4
Total32

Baseline characteristics

CharacteristicT2DM Individuals on DapagliflozinTotalNormal Glucose Tolerance (NGT) PlaceboNormal Glucose Tolerance (NGT) on DapagliflozinT2DM Individuals on Placebo
Age, Continuous57 years
STANDARD_DEVIATION 3
51.5 years
STANDARD_DEVIATION 2.95
47 years
STANDARD_DEVIATION 4.9
44 years
STANDARD_DEVIATION 2.2
58 years
STANDARD_DEVIATION 1.7
Ethnicity (NIH/OMB)
Hispanic or Latino
4 Participants14 Participants1 Participants6 Participants3 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
9 Participants18 Participants3 Participants2 Participants4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
1 Participants2 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
12 Participants30 Participants4 Participants7 Participants7 Participants
Region of Enrollment
United States
13 participants32 participants4 participants8 participants7 participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
13 Participants32 Participants4 Participants8 Participants7 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 130 / 70 / 80 / 4
other
Total, other adverse events
0 / 131 / 71 / 80 / 4
serious
Total, serious adverse events
0 / 130 / 70 / 80 / 4

Outcome results

Primary

Endogenous Glucose Production Measurement

Endogenous Glucose Production in NGT/T2DM subjects before and after dapagliflozin/Placebo administration from baseline to 240 minutes.

Time frame: 3 weeks

ArmMeasureValue (MEAN)Dispersion
T2DM Individuals on DapagliflozinEndogenous Glucose Production Measurement155 mg/dlStandard Deviation 6.4
T2DM Individuals on PlaceboEndogenous Glucose Production Measurement121 mg/dlStandard Deviation 6.2
Normal Glucose Tolerance (NGT) on DapagliflozinEndogenous Glucose Production Measurement104 mg/dlStandard Deviation 4.2
Normal Glucose Tolerance (NGT) PlaceboEndogenous Glucose Production Measurement98 mg/dlStandard Deviation 2
Secondary

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.

Time frame: Baseline to 3 weeks

ArmMeasureGroupValue (MEAN)Dispersion
T2DM Individuals on DapagliflozinRenal Glucose Production Measurement of ChangeBaseline0.09 mg/kg.minStandard Deviation 0.04
T2DM Individuals on DapagliflozinRenal Glucose Production Measurement of Change3 weeks0.17 mg/kg.minStandard Deviation 0.05
T2DM Individuals on PlaceboRenal Glucose Production Measurement of Change3 weeks0.03 mg/kg.minStandard Deviation 0.05
T2DM Individuals on PlaceboRenal Glucose Production Measurement of ChangeBaseline0.01 mg/kg.minStandard Deviation 0.03
Normal Glucose Tolerance (NGT) on DapagliflozinRenal Glucose Production Measurement of ChangeBaseline0.03 mg/kg.minStandard Deviation 0.09
Normal Glucose Tolerance (NGT) on DapagliflozinRenal Glucose Production Measurement of Change3 weeks0.09 mg/kg.minStandard Deviation 0.1
Normal Glucose Tolerance (NGT) PlaceboRenal Glucose Production Measurement of ChangeBaseline0.03 mg/kg.minStandard Deviation 0.09
Normal Glucose Tolerance (NGT) PlaceboRenal Glucose Production Measurement of Change3 weeks0.14 mg/kg.minStandard Deviation 0.12

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026