Pharmacokinetics Study of Dipeptidyl Peptidase 4 Inhibitor to Control Type 2 Diabetes Mellitus
Mechanism of Reduced Response to DPP-4 Inhibitor in Patients With Type 2 Diabetes Mellitus
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 4단계
연락처 및 위치
연구 장소
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Seoul, 대한민국, 130-709
- The Catholic University of Korea; St.Paul's Hospital
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Seoul, 대한민국, 137-701
- The Catholic University of Korea; Seoul St. Mary's Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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활성 비교기: study group
sitagliptin hypo-response patients
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Sitagliptin (100mg, per oral) once a day.
다른 이름들:
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가짜 비교기: control group
sitagliptin response patients
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Sitagliptin (100mg, per oral) once a day.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment
기간: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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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.
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0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment
기간: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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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.
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0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment
기간: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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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.
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0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment
기간: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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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.
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0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups
기간: 0, 15, 30, 45, 60 min post-dose
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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.
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0, 15, 30, 45, 60 min post-dose
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공동 작업자 및 조사자
수사관
- 수석 연구원: Ji Hyun Kim, Dr, The Catholic University of Korea
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- CMCENDO-01
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