Clinical trial NCT02420392: 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
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2015-04-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: To investigate the effect of dapagliflozin on the incretin sensitivity of the pancreatic beta cell.


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

Primary outcomes:
measure: Difference of incretin sensitivity of pancreatic beta cell measured by hyperglycemic clamp with GLP-1 and GIP infusion
timeFrame: From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
Secondary outcomes:
measure: First phase insulin/C-peptide response
timeFrame: From 0 to 10 minutes of hyperglycemic clamp
measure: Second phase insulin/C-peptide response
timeFrame: From 10 to 60 minutes of hyperglycemic clamp
measure: Area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp
timeFrame: From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
measure: Area under the curve of insulin/C-peptide level during GIP infusion under hyperglycemic clamp
timeFrame: From 120 minutes to 180 minutes during GIP infusion under hyperglycemic clamp
measure: Difference of incretin sensitivity between diabetes patients and normal glucose tolerance subjects
timeFrame: From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
measure: Difference of first phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects
timeFrame: From 0 to 10 minutes of hyperglycemic clamp
measure: Difference of second phase insulin/C-peptide response between diabetes patients and normal glucose tolerance subjects
timeFrame: From 10 to 60 minutes of hyperglycemic clamp
measure: Difference of area under the curve of insulin level during GLP-1 infusion under hyperglycemic clamp between diabetes patients and normal glucose tolerance subjects
timeFrame: From 60 minutes to 120 minutes during GLP-1 infusion under hyperglycemic clamp
measure: 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
timeFrame: From 120 minutes to 180 minutes during GIP infusion under hyperglycemic clamp
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Young Min Cho, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: