Effects of Dapagliflozin on the Incretin Sensitivity of the Pancreatic Beta Cell
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Dapagliflozin
Sponsored by

About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 2
Eligibility Criteria
Inclusion Criteria:
- Type 2 diabetes for dapagliflozin arm
- Normal glucose tolerance (fasting plasma glucose <100 mgd/l, HbA1c <6.0%) for normal glucose tolerance arm
- Age 18 to 75 years
- BMI <35 kg/m2
- For type 2 diabetes patients, at least 3 months of treatment period and HbA1c 7.5 to 11.0% and treatment with lifestyle modification and/or metformin or sulfonylurea
Exclusion Criteria:
- Who is allergic to dapagliflozin
- Type 1 diabetes
- Patients with history of diabetic ketoacidosis
- Reduced renal function (eGFR <60ml/min/1.73m2)
- Taking loop diuretics or dehydrated patient
- History of hypotension when taking hypertensive medication
- Diagnosed with heart failure
- Diagnosed with cerebral infarction
- Taking insulin, DPP-4 inhibitor, GLP-1 analogue, pioglitazone, alpha-glucosidase inhibitor
- Above upper limit of normal hematocrit range (male 39-52%, female 36-48%)
- Pregnant or breastfeeding women
- History of recurrent genitourinary infection
- AST/ALT more than two fold increased above normal upper limit
- Hemolytic disorder
Sites / Locations
- Seoul National University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Dapagliflozin treatment
Normal glucose tolerance
Arm Description
Test incretin sensitivity after dapagliflozin treatment in type 2 diabetes patients
Test incretin sensitivity in subjects with normal glucose tolerance
Outcomes
Primary Outcome Measures
Difference of incretin sensitivity of pancreatic beta cell measured by hyperglycemic clamp with GLP-1 and GIP infusion
Area under the curve of C-peptide level during GLP-1 infusion under hyperglycemic clamp
Secondary Outcome Measures
First phase insulin/C-peptide response
Second phase insulin/C-peptide response
Area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp
Area under the curve of insulin/C-peptide level during GIP infusion under hyperglycemic clamp
Difference of incretin sensitivity between diabetes patients and normal glucose tolerance subjects
Area under the curve of C-peptide level during GLP-1 infusion under hyperglycemic clamp
Difference of first phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects
Difference of second phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects
Difference of area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp between diabetes patients and normal glucose tolerance subjects
Difference of Area under the curve of insulin/C-peptide level during GIP infusion under hyperglycemic clamp between diabetes patients and normal glucose tolerance subjects
Full Information
NCT ID
NCT02420392
First Posted
April 11, 2015
Last Updated
April 20, 2016
Sponsor
Seoul National University Hospital
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT02420392
Brief Title
Effects of Dapagliflozin on the Incretin Sensitivity of the Pancreatic Beta Cell
Official Title
Effects of Dapagliflozin on the Incretin Sensitivity of the Pancreatic Beta Cell
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Hospital
Collaborators
AstraZeneca
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To investigate the effect of dapagliflozin on the incretin sensitivity of the pancreatic beta cell.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dapagliflozin treatment
Arm Type
Experimental
Arm Description
Test incretin sensitivity after dapagliflozin treatment in type 2 diabetes patients
Arm Title
Normal glucose tolerance
Arm Type
No Intervention
Arm Description
Test incretin sensitivity in subjects with normal glucose tolerance
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Intervention Description
8 weeks treatment of dapagliflozin added to the type 2 diabetes patients with unsufficiently controlled with metformin or sulfonylurea
Primary Outcome Measure Information:
Title
Difference of incretin sensitivity of pancreatic beta cell measured by hyperglycemic clamp with GLP-1 and GIP infusion
Description
Area under the curve of C-peptide level during GLP-1 infusion under hyperglycemic clamp
Time Frame
From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
Secondary Outcome Measure Information:
Title
First phase insulin/C-peptide response
Time Frame
From 0 to 10 minutes of hyperglycemic clamp
Title
Second phase insulin/C-peptide response
Time Frame
From 10 to 60 minutes of hyperglycemic clamp
Title
Area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp
Time Frame
From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
Title
Area under the curve of insulin/C-peptide level during GIP infusion under hyperglycemic clamp
Time Frame
From 120 minutes to 180 minutes during GIP infusion under hyperglycemic clamp
Title
Difference of incretin sensitivity between diabetes patients and normal glucose tolerance subjects
Description
Area under the curve of C-peptide level during GLP-1 infusion under hyperglycemic clamp
Time Frame
From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
Title
Difference of first phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects
Time Frame
From 0 to 10 minutes of hyperglycemic clamp
Title
Difference of second phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects
Time Frame
From 10 to 60 minutes of hyperglycemic clamp
Title
Difference of area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp between diabetes patients and normal glucose tolerance subjects
Time Frame
From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
Title
Difference of Area under the curve of insulin/C-peptide level during GIP infusion under hyperglycemic clamp between diabetes patients and normal glucose tolerance subjects
Time Frame
From 120 minutes to 180 minutes during GIP infusion under hyperglycemic clamp
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Type 2 diabetes for dapagliflozin arm
Normal glucose tolerance (fasting plasma glucose <100 mgd/l, HbA1c <6.0%) for normal glucose tolerance arm
Age 18 to 75 years
BMI <35 kg/m2
For type 2 diabetes patients, at least 3 months of treatment period and HbA1c 7.5 to 11.0% and treatment with lifestyle modification and/or metformin or sulfonylurea
Exclusion Criteria:
Who is allergic to dapagliflozin
Type 1 diabetes
Patients with history of diabetic ketoacidosis
Reduced renal function (eGFR <60ml/min/1.73m2)
Taking loop diuretics or dehydrated patient
History of hypotension when taking hypertensive medication
Diagnosed with heart failure
Diagnosed with cerebral infarction
Taking insulin, DPP-4 inhibitor, GLP-1 analogue, pioglitazone, alpha-glucosidase inhibitor
Above upper limit of normal hematocrit range (male 39-52%, female 36-48%)
Pregnant or breastfeeding women
History of recurrent genitourinary infection
AST/ALT more than two fold increased above normal upper limit
Hemolytic disorder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Young Min Cho, M.D., Ph.D.
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
Effects of Dapagliflozin on the Incretin Sensitivity of the Pancreatic Beta Cell
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