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
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
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Seoul、大韓民国、130-709
- The Catholic University of Korea; St.Paul's Hospital
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Seoul、大韓民国、137-701
- The Catholic University of Korea; Seoul St. Mary's Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：study group
sitagliptin hypo-response patients
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Sitagliptin (100mg, per oral) once a day.
他の名前：
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偽コンパレータ：control group
sitagliptin response patients
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Sitagliptin (100mg, per oral) once a day.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment
時間枠：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
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Ji Hyun Kim, Dr、The Catholic University of Korea
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CMCENDO-01
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