Effects of Dapagliflozin on the Incretin Sensitivity of the Pancreatic Beta Cell

Study Overview
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Brief Summary
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To investigate the effect of dapagliflozin on the incretin sensitivity of the pancreatic beta cell.

Official Title
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Effects of Dapagliflozin on the Incretin Sensitivity of the Pancreatic Beta Cell

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin treatment<br>Test incretin sensitivity after dapagliflozin treatment in type 2 diabetes patients | Drug: Dapagliflozin<br>* 8 weeks treatment of dapagliflozin added to the type 2 diabetes patients with unsufficiently controlled with metformin or sulfonylurea<br>|
| No Intervention: Normal glucose tolerance<br>Test incretin sensitivity in subjects with normal glucose tolerance | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First phase insulin/C-peptide response |  | From 0 to 10 minutes of hyperglycemic clamp | 
| Second phase insulin/C-peptide response |  | From 10 to 60 minutes of hyperglycemic clamp | 
| Area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp |  | From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp | 
| Area under the curve of insulin/C-peptide level during GIP infusion under hyperglycemic clamp |  | From 120 minutes to 180 minutes 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 | From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp | 
| Difference of first phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects |  | From 0 to 10 minutes of hyperglycemic clamp | 
| Difference of second phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects |  | From 10 to 60 minutes of hyperglycemic clamp | 
| Difference of area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp between diabetes patients and normal glucose tolerance subjects |  | From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp | 
| 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 |  | From 120 minutes to 180 minutes during GIP infusion under hyperglycemic clamp |