Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes mellitus, Dipeptidyl peptidase IV inhibitors, Glucagon-like peptide 1
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.
Interventions
DRUGSitagliptin
Sitagliptin (100mg, per oral) once a day.
Sponsors
Merck Sharp & Dohme LLC
The Catholic University of Korea
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose | 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 | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose | 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 | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose | 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 | 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose | 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
| Measure | Time frame | Description |
|---|---|---|
| Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | 0, 15, 30, 45, 60 min post-dose | 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. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-responder Sitagliptin non-response patients | 12 |
| Responder Sitagliptin response patients | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Non-responder | Responder | Total |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 5.7 | 57.4 years STANDARD_DEVIATION 7 | 58.1 years STANDARD_DEVIATION 6.3 |
| Body mass index | 25.1 kg/m^2 STANDARD_DEVIATION 1.7 | 24.4 kg/m^2 STANDARD_DEVIATION 3.8 | 24.8 kg/m^2 STANDARD_DEVIATION 2.9 |
| Duration of diabetes mellitus | 7.2 years STANDARD_DEVIATION 5.5 | 5.2 years STANDARD_DEVIATION 2.7 | 6.2 years STANDARD_DEVIATION 4.4 |
| HbA1c | 7.7 % STANDARD_DEVIATION 0.6 | 6.6 % STANDARD_DEVIATION 0.7 | 7.2 % STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
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.
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | baseline AUC total GLP-1 | 5766.5 pmol*min/L | Standard Deviation 4229.7 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | post-dose AUC total GIP | 8784.6 pmol*min/L | Standard Deviation 2449.2 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | post-dose AUC active GLP-1 | 3898.5 pmol*min/L | Standard Deviation 1547.5 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | ΔAUC active GLP-1 | 1716.8 pmol*min/L | Standard Deviation 1350.7 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | baseline AUC total GIP | 10216.7 pmol*min/L | Standard Deviation 4226.1 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | ΔAUC total GLP-1 | -972.0 pmol*min/L | Standard Deviation 1030.4 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | post-dose AUC total GLP-1 | 4794.5 pmol*min/L | Standard Deviation 4949.8 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | ΔAUC total GIP | -1432.1 pmol*min/L | Standard Deviation 2738 |
| Non-responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | baseline AUC active GLP-1 | 2181.7 pmol*min/L | Standard Deviation 1099.6 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | ΔAUC total GIP | -1646.2 pmol*min/L | Standard Deviation 1817.7 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | baseline AUC active GLP-1 | 1578.2 pmol*min/L | Standard Deviation 807.5 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | baseline AUC total GLP-1 | 3680.2 pmol*min/L | Standard Deviation 3209.3 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | baseline AUC total GIP | 7575.6 pmol*min/L | Standard Deviation 4608.3 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | post-dose AUC active GLP-1 | 3535.1 pmol*min/L | Standard Deviation 2769.1 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | post-dose AUC total GLP-1 | 3373.6 pmol*min/L | Standard Deviation 3169.8 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | post-dose AUC total GIP | 5929.4 pmol*min/L | Standard Deviation 4711.2 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | ΔAUC active GLP-1 | 1956.8 pmol*min/L | Standard Deviation 2910.7 |
| Responder | Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment | ΔAUC total GLP-1 | -306.7 pmol*min/L | Standard Deviation 883.6 |
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.
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 0 min | 7.0 pmol/L | Standard Deviation 6.6 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 15 min | 10.6 pmol/L | Standard Deviation 8 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 30 min | 15.7 pmol/L | Standard Deviation 10.3 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 45 min | 14.7 pmol/L | Standard Deviation 8.2 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 60 min | 13.7 pmol/L | Standard Deviation 6.8 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 90 min | 10.6 pmol/L | Standard Deviation 5.4 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 120 min | 11.3 pmol/L | Standard Deviation 6.8 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 180 min | 12.6 pmol/L | Standard Deviation 8.7 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 0 min | 13.6 pmol/L | Standard Deviation 9.4 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 15 min | 24.0 pmol/L | Standard Deviation 16 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 30 min | 28.4 pmol/L | Standard Deviation 11 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 45 min | 22.4 pmol/L | Standard Deviation 11.3 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 60 min | 21.7 pmol/L | Standard Deviation 11.3 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 90 min | 19.3 pmol/L | Standard Deviation 10.8 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 120 min | 22.0 pmol/L | Standard Deviation 10.8 |
| Non-responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 180 min | 20.5 pmol/L | Standard Deviation 8.3 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 180 min | 13.5 pmol/L | Standard Deviation 7 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 0 min | 6.1 pmol/L | Standard Deviation 1.9 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 0 min | 10.5 pmol/L | Standard Deviation 4.5 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 15 min | 14.1 pmol/L | Standard Deviation 24.4 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 60 min | 22.8 pmol/L | Standard Deviation 27.1 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 30 min | 14.3 pmol/L | Standard Deviation 20.2 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 15 min | 26.0 pmol/L | Standard Deviation 39.9 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 45 min | 9.3 pmol/L | Standard Deviation 4.3 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 120 min | 16.4 pmol/L | Standard Deviation 6.5 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 60 min | 8.4 pmol/L | Standard Deviation 2.7 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 30 min | 34.3 pmol/L | Standard Deviation 53.1 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 90 min | 7.6 pmol/L | Standard Deviation 2.1 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 90 min | 16.5 pmol/L | Standard Deviation 7.6 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 120 min | 7.4 pmol/L | Standard Deviation 2.1 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | post-dose 45 min | 27.1 pmol/L | Standard Deviation 37.6 |
| Responder | Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment | baseline 180 min | 7.1 pmol/L | Standard Deviation 2.5 |
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.
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 90 min | 26.2 pmol/L | Standard Deviation 30.1 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 15 min | 30.5 pmol/L | Standard Deviation 26.1 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 30 min | 36.2 pmol/L | Standard Deviation 26.8 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 45 min | 30.9 pmol/L | Standard Deviation 18.9 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 60 min | 31.8 pmol/L | Standard Deviation 20.9 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 90 min | 31.8 pmol/L | Standard Deviation 24.3 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 120 min | 31.3 pmol/L | Standard Deviation 22.2 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 180 min | 34.5 pmol/L | Standard Deviation 28.3 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 0 min | 23.0 pmol/L | Standard Deviation 27.8 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 15 min | 28.4 pmol/L | Standard Deviation 27.9 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 30 min | 26.3 pmol/L | Standard Deviation 19.4 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 45 min | 29.2 pmol/L | Standard Deviation 27.2 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 60 min | 26.5 pmol/L | Standard Deviation 29.1 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 120 min | 26.7 pmol/L | Standard Deviation 30.5 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 180 min | 26.0 pmol/L | Standard Deviation 25.8 |
| Non-responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 0 min | 25.6 pmol/L | Standard Deviation 26.9 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 120 min | 18.7 pmol/L | Standard Deviation 16.1 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 0 min | 15.6 pmol/L | Standard Deviation 16.2 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 0 min | 16.4 pmol/L | Standard Deviation 17.6 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 15 min | 20.4 pmol/L | Standard Deviation 19.7 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 60 min | 18.6 pmol/L | Standard Deviation 19.2 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 30 min | 22.4 pmol/L | Standard Deviation 17 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 15 min | 20.6 pmol/L | Standard Deviation 20.7 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 45 min | 25.5 pmol/L | Standard Deviation 21 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 90 min | 18.1 pmol/L | Standard Deviation 17 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 60 min | 21.7 pmol/L | Standard Deviation 19.9 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 30 min | 20.6 pmol/L | Standard Deviation 18.1 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 90 min | 19.2 pmol/L | Standard Deviation 17.1 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 180 min | 18.2 pmol/L | Standard Deviation 18.2 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 120 min | 19.9 pmol/L | Standard Deviation 18 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | post-dose 45 min | 18.9 pmol/L | Standard Deviation 18.3 |
| Responder | Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment | baseline 180 min | 19.3 pmol/L | Standard Deviation 17.5 |
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.
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 60 min | 61.5 pmol/L | Standard Deviation 26.1 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 15 min | 42.3 pmol/L | Standard Deviation 30.7 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 30 min | 109.6 pmol/L | Standard Deviation 49.9 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 45 min | 109.6 pmol/L | Standard Deviation 43.5 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 60 min | 83.0 pmol/L | Standard Deviation 22.6 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 90 min | 66.3 pmol/L | Standard Deviation 22.6 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 120 min | 61.7 pmol/L | Standard Deviation 27.9 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 180 min | 39.9 pmol/L | Standard Deviation 17.9 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 0 min | 10.5 pmol/L | Standard Deviation 4 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 15 min | 34.2 pmol/L | Standard Deviation 14 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 30 min | 90.8 pmol/L | Standard Deviation 34.7 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 45 min | 77.6 pmol/L | Standard Deviation 37.8 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 90 min | 44.2 pmol/L | Standard Deviation 15.7 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 120 min | 43.8 pmol/L | Standard Deviation 15.3 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 180 min | 32.8 pmol/L | Standard Deviation 9.2 |
| Non-responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 0 min | 13.8 pmol/L | Standard Deviation 4.5 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 60 min | 37.7 pmol/L | Standard Deviation 25.4 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 0 min | 12.3 pmol/L | Standard Deviation 6.9 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 0 min | 10.3 pmol/L | Standard Deviation 5.3 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 15 min | 40.3 pmol/L | Standard Deviation 28.1 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 120 min | 35.0 pmol/L | Standard Deviation 39 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 30 min | 60.2 pmol/L | Standard Deviation 39.8 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 15 min | 26.3 pmol/L | Standard Deviation 15.6 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 45 min | 54.1 pmol/L | Standard Deviation 37.9 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 90 min | 38.2 pmol/L | Standard Deviation 41.6 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 60 min | 52.0 pmol/L | Standard Deviation 37.7 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 30 min | 33.1 pmol/L | Standard Deviation 23.5 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 90 min | 44.7 pmol/L | Standard Deviation 25.5 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 180 min | 24.7 pmol/L | Standard Deviation 25.6 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 120 min | 39.0 pmol/L | Standard Deviation 23.9 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | post-dose 45 min | 38.5 pmol/L | Standard Deviation 23.5 |
| Responder | Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment | baseline 180 min | 30.0 pmol/L | Standard Deviation 18.2 |
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.
Time frame: 0, 15, 30, 45, 60 min post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | baseline | 100 percentage of DPP4 activity | Standard Deviation 0 |
| Non-responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 0 min | 67.2 percentage of DPP4 activity | Standard Deviation 13.2 |
| Non-responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 15 min | 67.3 percentage of DPP4 activity | Standard Deviation 18.6 |
| Non-responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 30 min | 67.7 percentage of DPP4 activity | Standard Deviation 13.1 |
| Non-responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 45 min | 59.6 percentage of DPP4 activity | Standard Deviation 18.7 |
| Non-responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 60 min | 58.5 percentage of DPP4 activity | Standard Deviation 12.5 |
| Responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 45 min | 33.5 percentage of DPP4 activity | Standard Deviation 8.4 |
| Responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | baseline | 100 percentage of DPP4 activity | Standard Deviation 0 |
| Responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 30 min | 38.7 percentage of DPP4 activity | Standard Deviation 9.2 |
| Responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 0 min | 40.5 percentage of DPP4 activity | Standard Deviation 9.9 |
| Responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 60 min | 44.3 percentage of DPP4 activity | Standard Deviation 7.7 |
| Responder | Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups | Sitagliptin 15 min | 39.2 percentage of DPP4 activity | Standard Deviation 11.2 |