Diabetes Mellitus, Type 2
Conditions
Brief summary
To investigate the effect of dapagliflozin on the incretin sensitivity of the pancreatic beta cell.
Interventions
DRUGDapagliflozin
8 weeks treatment of dapagliflozin added to the type 2 diabetes patients with unsufficiently controlled with metformin or sulfonylurea
Sponsors
AstraZeneca
Seoul National University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference of incretin sensitivity of pancreatic beta cell measured by hyperglycemic clamp with GLP-1 and GIP infusion | From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp | Area under the curve of C-peptide level during GLP-1 infusion under hyperglycemic clamp |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp | Area under the curve of C-peptide level during GLP-1 infusion under hyperglycemic clamp |
| First phase insulin/C-peptide response | 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 | — |
| Difference of first phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects | From 0 to 10 minutes of hyperglycemic clamp | — |
Countries
South Korea
Outcome results
None listed