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Completed

NCT Number: NCT01449747

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

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

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Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

20 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

The Catholic University of Korea; Seoul St. Mary's Hospital, Seoul, South Korea

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.
  • 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

Treatment and study plan

Sitagliptin

Drug

Sitagliptin (100mg, per oral) once a day.

Other names: Januvia

Primary outcomes

  1. Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment

    Time frame: 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.

  2. Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment

    Time frame: 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.

  3. Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment

    Time frame: 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.

  4. Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment

    Time frame: 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 outcomes

  1. Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

The Catholic University of Korea

Other

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

Mechanism of Reduced Response to DPP-4 Inhibitor in Patients With Type 2 Diabetes Mellitus

Important dates

Study start
2011
Primary completion
2014
Study completion
2015
First posted
Oct 10, 2011
Registry last updated
Dec 14, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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