Efficacy of Sitagliptin and Glibenclamide on the Glucose Variability in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431-355)

Study Overview
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Brief Summary
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This is a study of the efficacy of sitagliptin and glibenclamide in a short-term treatment on the glucose variability using continuous glucose monitoring (CGM) in Japanese participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is that treatment with sitagliptin will be superior to treatment with glibenclamide in the change from baseline in mean amplitude of glycemic excursions (MAGE) through continuous glucose monitoring (CGM) after 13 days of treatment.

Official Title
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A Randomized, Open-label, Comparative Clinical Trial to Study the Efficacy of Sitagliptin and Glibenclamide in a Short Term Treatment on the Daily Glucose Variability Using Continuous Glucose Monitoring (CGM) in Japanese Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Glibenclamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese participants with a diagnosis of Type 2 diabetes mellitus Exclusion Criteria: History of Type 1 diabetes mellitus or ketoacidosis History of insulin or thiazolidinedione (including fixed-dose drug combinations containing one of these drugs) in the 12 weeks before study participation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin 50 mg<br>Sitagliptin 50 mg administered orally once daily before breakfast for 14 days. | Drug: Sitagliptin<br>* Sitagliptin 50 mg orally once a day before breakfast for 14 days<br>* Other names: MK-0431;|
| Active Comparator: Glibenclamide 2.50 mg TDD<br>Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days. TDD = Total daily dose. | Drug: Glibenclamide<br>* Glibenclamide 1.25 mg orally twice a day (2.5 mg/day) before breakfast and dinner for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Amplitude of Glycemic Excursions (MAGE) at Day 13 | MAGE is a popular metric for assessment of major (e.g., postprandial) glucose swings. MAGE is calculated as the average of differences between consecutive glucose peaks and nadirs greater than 1 standard deviation (SD) of 24-hour mean glucose. In this assessment, glucose levels were determined using continuous glucose monitoring (CGM) over 24 hours at Baseline and Day 13; CGM values were further corrected for blood glucose values obtained via participant-administered finger-stick. Least squares (LS) means values were derived from a constrained longitudinal analysis model. A negative (-) change from Baseline to Day 13 indicates improvement of the assessed outcome. | Baseline (Day -2) and Day 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Standard Deviation of Blood Glucose Levels | SD is a popular metric for assessment of postprandial glucose swings. The SD of all glycemic excursions over 24 hours (i.e., total of 288 glucose values over 24 hours) was determined for Baseline and Day 13. Original values were obtained using CGM and corrected for blood glucose values obtained via participant-administered finger-stick. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from Baseline to Day 13 indicates improvement of the assessed outcome. | Baseline (Day -2) and Day 13 | 
| Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | The peak postprandial glucose level during the 3 hours post meal minus the preprandial glucose level 1 hour before meal was determined for corrected CGM values at Baseline and Day 13 for breakfast, lunch, and dinner. Meals were standardized with respect to total calories, and protein, fat, and carbohydrate composition as well as timing of administration. CGM values were corrected using a participant-administered finger-stick test for blood glucose. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from baseline to Day 13 indicates better control of postprandial glucose. | Baseline (Day -2) and Day 13 | 
| Change From Baseline in 24-hour Mean Glucose Level | The mean glucose level over 24-hours at Baseline and Day 13 was determined using CGM values corrected for participant-administered finger-stick values. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from Baseline to Day 13 indicates improvement of the assessed outcome. | Baseline (Day -2) and Day 13 | 
| Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | Hypoglycemia, defined as low blood glucose, is a common side effect of medications used to treat diabetes mellitus type 2. The percentage of hypoglycemic corrected CGM readings (sensor glucose <70, <60, <50 mg/dL) over a 24-hour period were determined at baseline and Day 13. CGM values were corrected using a participant-administered finger-stick test for blood glucose. LS mean values were derived from a constrained longitudinal analysis model. A negative (-) change from baseline to Day 13 indicates improvement in occurrence of hypoglycemia. | Baseline (Day -2) and Day 13 |