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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| study group | Active Comparator | sitagliptin hypo-response patients |
|
| control group | Sham Comparator | sitagliptin response patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitagliptin | Drug | Sitagliptin (100mg, per oral) once a day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
| 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. | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
| 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. | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
| 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. | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Type 2 diabetic patients with less than 15 yrs of disease duration
BMI between 22-27 kg/m2
HbA1c ≤ 9% at recruitment
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
Reduced response to sitagliptin should be made a decision by investigators after understanding the condition of patients surely.
2. Control group
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ji Hyun Kim, Dr | The Catholic University of Korea | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Catholic University of Korea; St.Paul's Hospital | Seoul | 130-709 | South Korea | |||
| The Catholic University of Korea; Seoul St. Mary's Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | Non-responder | Sitagliptin non-response patients |
| FG001 | Responder | Sitagliptin response patients |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Non-responder | Sitagliptin non-response patients |
| BG001 | Responder | Sitagliptin response patients |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | pmol/L | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Non-responder | Sitagliptin non-response patients |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ji Hyun Kim | The Catholic University of Korea | 82-2-961-4534 | kjhyun@catholic.ac.kr |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| 0, 15, 30, 45, 60 min post-dose |
| Seoul |
| 137-701 |
| South Korea |
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Duration of diabetes mellitus | Mean | Standard Deviation | years |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| HbA1c | Mean | Standard Deviation | % |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | percentage of DPP4 activity | 0, 15, 30, 45, 60 min post-dose |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pmol/L | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pmol/L | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | pmol*min/L | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Responder | Sitagliptin response patients | 0 | 12 | 0 | 12 |
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| D004700 | Endocrine System Diseases |
| D011719 |
| Pyrazines |
| Sitagliptin 15 min |
|
| Sitagliptin 30 min |
|
| Sitagliptin 45 min |
|
| Sitagliptin 60 min |
|
| baseline 30 min |
|
| baseline 45 min |
|
| baseline 60 min |
|
| baseline 90 min |
|
| baseline 120 min |
|
| baseline 180 min |
|
| post-dose 0 min |
|
| post-dose 15 min |
|
| post-dose 30 min |
|
| post-dose 45 min |
|
| post-dose 60 min |
|
| post-dose 90 min |
|
| post-dose 120 min |
|
| post-dose 180 min |
|
| baseline 30 min |
|
| baseline 45 min |
|
| baseline 60 min |
|
| baseline 90 min |
|
| baseline 120 min |
|
| baseline 180 min |
|
| post-dose 0 min |
|
| post-dose 15 min |
|
| post-dose 30 min |
|
| post-dose 45 min |
|
| post-dose 60 min |
|
| post-dose 90 min |
|
| post-dose 120 min |
|
| post-dose 180 min |
|
| baseline AUC total GIP |
|
| post-dose AUC active GLP-1 |
|
| post-dose AUC total GLP-1 |
|
| post-dose AUC total GIP |
|
| ΔAUC active GLP-1 |
|
| ΔAUC total GLP-1 |
|
| ΔAUC total GIP |
|