Trial Outcomes & Findings for Efficacy of Sitagliptin and Glibenclamide on the Glucose Variability in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431-355) (NCT NCT02318693)
NCT ID: NCT02318693
Last Updated: 2018-08-21
Results Overview
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.
COMPLETED
PHASE4
53 participants
Baseline (Day -2) and Day 13
2018-08-21
Participant Flow
Screening for study inclusion was performed over a 4-week period. Adults with type 2 diabetes were randomized into the study.
Participant milestones
| Measure |
Sitagliptin 50 mg
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days. TDD = Total daily dose.
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
27
|
|
Overall Study
Treated
|
26
|
26
|
|
Overall Study
COMPLETED
|
26
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Sitagliptin 50 mg
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days. TDD = Total daily dose.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Efficacy of Sitagliptin and Glibenclamide on the Glucose Variability in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431-355)
Baseline characteristics by cohort
| Measure |
Sitagliptin 50 mg
n=26 Participants
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
n=26 Participants
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days.
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.2 Years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
59.5 Years
STANDARD_DEVIATION 10.7 • n=7 Participants
|
59.8 Years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
|
Age, Customized
<65 years
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Body Weight
|
70.2 kg
STANDARD_DEVIATION 8.2 • n=5 Participants
|
70.7 kg
STANDARD_DEVIATION 11.2 • n=7 Participants
|
70.5 kg
STANDARD_DEVIATION 9.7 • n=5 Participants
|
|
Height
|
169.5 cm
STANDARD_DEVIATION 5.4 • n=5 Participants
|
169.3 cm
STANDARD_DEVIATION 5.3 • n=7 Participants
|
169.4 cm
STANDARD_DEVIATION 5.3 • n=5 Participants
|
|
Body Mass Index
|
24.4 kg/m^2
STANDARD_DEVIATION 2.1 • n=5 Participants
|
24.6 kg/m^2
STANDARD_DEVIATION 3.0 • n=7 Participants
|
24.5 kg/m^2
STANDARD_DEVIATION 2.6 • n=5 Participants
|
|
Duration of Diabetes Mellitus
|
6.4 Years
STANDARD_DEVIATION 5.4 • n=5 Participants
|
9.9 Years
STANDARD_DEVIATION 5.5 • n=7 Participants
|
8.2 Years
STANDARD_DEVIATION 5.7 • n=5 Participants
|
|
Smoking Status
Current Smoker
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Smoking Status
Ex-Smoker
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Smoking Status
Never Smoked
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Alcohol Consumption
0
|
8 Drinks/week
n=5 Participants
|
5 Drinks/week
n=7 Participants
|
13 Drinks/week
n=5 Participants
|
|
Alcohol Consumption
1 to 4
|
9 Drinks/week
n=5 Participants
|
13 Drinks/week
n=7 Participants
|
22 Drinks/week
n=5 Participants
|
|
Alcohol Consumption
>5
|
9 Drinks/week
n=5 Participants
|
8 Drinks/week
n=7 Participants
|
17 Drinks/week
n=5 Participants
|
|
Hemoglobin A1C (HbA1C)
|
7.7 %
STANDARD_DEVIATION 0.5 • n=5 Participants
|
7.9 %
STANDARD_DEVIATION 0.6 • n=7 Participants
|
7.8 %
STANDARD_DEVIATION 0.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day -2) and Day 13Population: The FAS population consisting of all randomized participants who received at least one dose of study treatment, with at least one post-randomization/post-treatment observation for the analysis, and with applicable baseline data was used for analysis.
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.
Outcome measures
| Measure |
Sitagliptin 50 mg
n=26 Participants
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
n=26 Participants
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days.
|
|---|---|---|
|
Change From Baseline in Mean Amplitude of Glycemic Excursions (MAGE) at Day 13
|
-18.5 mg/dL
Interval -30.0 to -7.1
|
-9.7 mg/dL
Interval -21.1 to 1.6
|
SECONDARY outcome
Timeframe: Baseline (Day -2) and Day 13Population: The FAS population consisting of all randomized participants who received at least one dose of study treatment, with at least one post-randomization/post-treatment observation for the analysis, and with applicable baseline data was used for analysis.
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.
Outcome measures
| Measure |
Sitagliptin 50 mg
n=26 Participants
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
n=26 Participants
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days.
|
|---|---|---|
|
Change From Baseline in the Standard Deviation of Blood Glucose Levels
|
-10.2 mg/dL
Interval -14.4 to -6.0
|
-4.2 mg/dL
Interval -8.4 to -0.1
|
SECONDARY outcome
Timeframe: Baseline (Day -2) and Day 13Population: The FAS population consisting of all randomized participants who received at least one dose of study treatment, with at least one post-randomization/post-treatment observation for the analysis, and with applicable baseline data was used for analysis.
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.
Outcome measures
| Measure |
Sitagliptin 50 mg
n=26 Participants
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
n=26 Participants
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days.
|
|---|---|---|
|
Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal
Lunch
|
-13.2 mg/dL
Interval -24.0 to -2.3
|
1.2 mg/dL
Interval -9.6 to 11.9
|
|
Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal
Breakfast
|
-24.8 mg/dL
Interval -34.1 to -15.6
|
-12.0 mg/dL
Interval -21.1 to -2.9
|
|
Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal
Dinner
|
-9.0 mg/dL
Interval -20.9 to 2.9
|
-14.1 mg/dL
Interval -25.9 to -2.3
|
SECONDARY outcome
Timeframe: Baseline (Day -2) and Day 13Population: The FAS population consisting of all randomized participants who received at least one dose of study treatment, with at least one post-randomization/post-treatment observation for the analysis, and with applicable baseline data was used for analysis.
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.
Outcome measures
| Measure |
Sitagliptin 50 mg
n=26 Participants
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
n=26 Participants
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days.
|
|---|---|---|
|
Change From Baseline in 24-hour Mean Glucose Level
|
-19.1 mg/dL
Interval -28.5 to -9.7
|
-34.8 mg/dL
Interval -44.0 to -25.5
|
SECONDARY outcome
Timeframe: Baseline (Day -2) and Day 13Population: The FAS population consisting of all randomized participants who received at least one dose of study treatment, with at least one post-randomization/post-treatment observation for the analysis, and with applicable baseline data was used for analysis.
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.
Outcome measures
| Measure |
Sitagliptin 50 mg
n=26 Participants
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
n=26 Participants
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days.
|
|---|---|---|
|
Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL)
<70 mg/dL
|
-0.3 Percent change
Interval -1.6 to 1.0
|
0.8 Percent change
Interval -0.5 to 2.1
|
|
Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL)
<60 mg/dL
|
-0.4 Percent change
Interval -1.3 to 0.5
|
0.2 Percent change
Interval -0.7 to 1.1
|
|
Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL)
<50 mg/dL
|
-0.3 Percent change
Interval -0.8 to 0.2
|
-0.3 Percent change
Interval -0.7 to 0.2
|
Adverse Events
Sitagliptin 50 mg
Glibenclamide 2.50 mg TDD
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sitagliptin 50 mg
n=26 participants at risk
Sitagliptin 50 mg administered orally once daily before breakfast for 14 days.
|
Glibenclamide 2.50 mg TDD
n=26 participants at risk
Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days.
|
|---|---|---|
|
Infections and infestations
Periodontitis
|
7.7%
2/26 • Number of events 2 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
0.00%
0/26 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
7.7%
2/26 • Number of events 5 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
11.5%
3/26 • Number of events 4 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
0.00%
0/26 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
7.7%
2/26 • Number of events 2 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
38.5%
10/26 • Number of events 10 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
23.1%
6/26 • Number of events 6 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
7.7%
2/26 • Number of events 2 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
7.7%
2/26 • Number of events 2 • Up to 4 weeks
The All Subjects as Treated (ASaT) population consisting of all participants who received at least one dose of study treatment was used for analysis of safety.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential may be deleted prior to submission; this confidentiality does not include efficacy and safety results.
- Publication restrictions are in place
Restriction type: OTHER