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Pharmacokinetics Study of Dipeptidyl Peptidase 4 Inhibitor to Control Type 2 Diabetes Mellitus

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Sitagliptin
Sponsored by
The Catholic University of Korea
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 diabetes mellitus, Dipeptidyl peptidase IV inhibitors, Glucagon-like peptide 1

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Type 2 diabetic patients with less than 15 yrs of disease duration
  • BMI between 22-27 kg/m2

  • HbA1c ≤ 9% at recruitment

    1. Study group

After change sulfonylurea to sitagliptin in case of metformin and sulfonylurea therapy

  1. Increase of fasting blood glucose over 20 mg/dL or postprandial glucose over 30 mg/dL within several days or

  2. Increase of HbA1c over 1% within 2-3 months without abrupt increase of blood glucose levels within several days

    • Sulfonylurea dose : less than glimepiride 4mg or gliclazide 120mg or glibenclamide 10mg
    • Metformin dose : 500~2000mg
  3. Reduced response to sitagliptin should be made a decision by investigators after understanding the condition of patients surely.

2. Control group

  • Age, sex, BMI matched patients with same condition of study patients
  • After change sulfonylurea to sitagliptin in case of metformin plus sulfonylurea therapy, no change of blood glucose levels like above or stable HbA1c change within 1% within 2-3 months

Exclusion Criteria:

  • Other causes of increase of blood glucose levels except drug change
  • Patients with history of insulin treatment
  • Patients taking thiazolidinediones, alpha-glucosidase inhibitors, GLP-1 analogue or DPP-4 inhibitors
  • Patients with renal, hepatic dysfunction
  • Patients with diabetic complications such as coronary heart disease, cerebrovascular disease, proliferative diabetic retinopathy or diabetic gastroparesis
  • Patients taking medications affecting glucose level

Sites / Locations

  • The Catholic University of Korea; St.Paul's Hospital
  • The Catholic University of Korea; Seoul St. Mary's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

study group

control group

Arm Description

sitagliptin hypo-response patients

sitagliptin response patients

Outcomes

Primary Outcome Measures

Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment
Plasma concentrations of active GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test (MTT). Second measurement of active GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment
Plasma concentrations of total GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment
Plasma concentrations of total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GIP were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment
Plasma concentrations of active GLP-1, total GLP-1 and total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurements were measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Comparisons were made using Area under the curve (AUC) values and incremental area under the curve (ΔAUC) of active GLP-1, total GLP-1 and total GIP before and after the addition of sitagliptin.

Secondary Outcome Measures

Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups
The DPP-4 activity was measured at baseline and 0, 15, 30, 45 and 60 min during the meal tolerance test. Second measurement of DPP-4 activity was measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Plasma DPP-4 activity during meal tolerance test is expressed as percentage activity relative to baseline. DPP-4 activity % was calculated using the following formula : (DPP-4 activity at time t / Baseline DPP-4 activity) × 100.

Full Information

First Posted
September 29, 2011
Last Updated
November 10, 2015
Sponsor
The Catholic University of Korea
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01449747
Brief Title
Pharmacokinetics Study of Dipeptidyl Peptidase 4 Inhibitor to Control Type 2 Diabetes Mellitus
Official Title
Mechanism of Reduced Response to DPP-4 Inhibitor in Patients With Type 2 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Catholic University of Korea
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to confirm the mechanism of reduced response to DPP-4 inhibitor in some patients with type 2 diabetes and evaluate appropriate patients to treat with DPP-4 inhibitor
Detailed Description
Sitagliptin, a DPP-4 inhibitor was used as an incretin enhancer in clinical practice first. In clinical trials, sitagliptin showed effective control of blood glucose level in type 2 diabetes and 100 mg once daily with metformin was similar to sulfonylurea (glipizide) with metformin in lowering HbA1c. Mostly in practice, stable blood glucose levels were maintained after change of sulfonylurea to sitagliptin in type 2 diabetes treatment. However, in some cases, there were abrupt severe hyperglycemia and uncontrolled blood glucose level after drug change to sitagliptin. Several mechanism could be considered for reduced response to DPP-4 inhibitor in some type 2 diabetes patients. Firstly, significantly reduced secretion of glucagon-like peptide 1 (GLP-1) more than expected in diabetes or functional defect of GLP-1 activity could be the mechanism of loss of GLP-1 effect irrespective of DPP-4. Secondly, mutation or functional defect of DPP-4 enzyme could not be inhibited by DPP-4 inhibitor. Thirdly, GLP-1 receptor mutation or other defect in β-cell responsiveness to GLP-1 leads to reduction of response to DPP-4 inhibitor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Type 2 diabetes mellitus, Dipeptidyl peptidase IV inhibitors, Glucagon-like peptide 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
study group
Arm Type
Active Comparator
Arm Description
sitagliptin hypo-response patients
Arm Title
control group
Arm Type
Sham Comparator
Arm Description
sitagliptin response patients
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
Januvia
Intervention Description
Sitagliptin (100mg, per oral) once a day.
Primary Outcome Measure Information:
Title
Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment
Description
Plasma concentrations of active GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test (MTT). Second measurement of active GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Time Frame
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Title
Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment
Description
Plasma concentrations of total GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Time Frame
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Title
Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment
Description
Plasma concentrations of total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GIP were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Time Frame
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Title
Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment
Description
Plasma concentrations of active GLP-1, total GLP-1 and total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurements were measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Comparisons were made using Area under the curve (AUC) values and incremental area under the curve (ΔAUC) of active GLP-1, total GLP-1 and total GIP before and after the addition of sitagliptin.
Time Frame
0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Secondary Outcome Measure Information:
Title
Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups
Description
The DPP-4 activity was measured at baseline and 0, 15, 30, 45 and 60 min during the meal tolerance test. Second measurement of DPP-4 activity was measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Plasma DPP-4 activity during meal tolerance test is expressed as percentage activity relative to baseline. DPP-4 activity % was calculated using the following formula : (DPP-4 activity at time t / Baseline DPP-4 activity) × 100.
Time Frame
0, 15, 30, 45, 60 min post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Type 2 diabetic patients with less than 15 yrs of disease duration BMI between 22-27 kg/m2 HbA1c ≤ 9% at recruitment Study group After change sulfonylurea to sitagliptin in case of metformin and sulfonylurea therapy Increase of fasting blood glucose over 20 mg/dL or postprandial glucose over 30 mg/dL within several days or Increase of HbA1c over 1% within 2-3 months without abrupt increase of blood glucose levels within several days Sulfonylurea dose : less than glimepiride 4mg or gliclazide 120mg or glibenclamide 10mg Metformin dose : 500~2000mg Reduced response to sitagliptin should be made a decision by investigators after understanding the condition of patients surely. 2. Control group Age, sex, BMI matched patients with same condition of study patients After change sulfonylurea to sitagliptin in case of metformin plus sulfonylurea therapy, no change of blood glucose levels like above or stable HbA1c change within 1% within 2-3 months Exclusion Criteria: Other causes of increase of blood glucose levels except drug change Patients with history of insulin treatment Patients taking thiazolidinediones, alpha-glucosidase inhibitors, GLP-1 analogue or DPP-4 inhibitors Patients with renal, hepatic dysfunction Patients with diabetic complications such as coronary heart disease, cerebrovascular disease, proliferative diabetic retinopathy or diabetic gastroparesis Patients taking medications affecting glucose level
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ji Hyun Kim, Dr
Organizational Affiliation
The Catholic University of Korea
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Catholic University of Korea; St.Paul's Hospital
City
Seoul
ZIP/Postal Code
130-709
Country
Korea, Republic of
Facility Name
The Catholic University of Korea; Seoul St. Mary's Hospital
City
Seoul
ZIP/Postal Code
137-701
Country
Korea, Republic of

12. IPD Sharing Statement

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Pharmacokinetics Study of Dipeptidyl Peptidase 4 Inhibitor to Control Type 2 Diabetes Mellitus

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