Type 2 Diabetes Mellitus
Conditions
Brief summary
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.
Interventions
DRUGSitagliptin
Sitagliptin 50 mg orally once a day before breakfast for 14 days
DRUGGlibenclamide
Glibenclamide 1.25 mg orally twice a day (2.5 mg/day) before breakfast and dinner for 14 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Amplitude of Glycemic Excursions (MAGE) at Day 13 | Baseline (Day -2) and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Standard Deviation of Blood Glucose Levels | Baseline (Day -2) and Day 13 | 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. |
| Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | Baseline (Day -2) and Day 13 | 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. |
| Change From Baseline in 24-hour Mean Glucose Level | Baseline (Day -2) and Day 13 | 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. |
| Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | Baseline (Day -2) and Day 13 | 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. |
Participant flow
Recruitment details
Screening for study inclusion was performed over a 4-week period. Adults with type 2 diabetes were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 50 mg Sitagliptin 50 mg administered orally once daily before breakfast for 14 days. | 26 |
| Glibenclamide 2.50 mg TDD Glibenclamide 1.25 mg administered orally twice daily (2.5 mg TDD) for 14 days. | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Sitagliptin 50 mg | Glibenclamide 2.50 mg TDD |
|---|---|---|---|
| Age, Continuous | 59.8 Years STANDARD_DEVIATION 9.5 | 60.2 Years STANDARD_DEVIATION 8.4 | 59.5 Years STANDARD_DEVIATION 10.7 |
| Age, Customized <65 years | 31 Participants | 15 Participants | 16 Participants |
| Age, Customized >=65 years | 21 Participants | 11 Participants | 10 Participants |
| Alcohol Consumption 0 | 13 Drinks/week | 8 Drinks/week | 5 Drinks/week |
| Alcohol Consumption 1 to 4 | 22 Drinks/week | 9 Drinks/week | 13 Drinks/week |
| Alcohol Consumption >5 | 17 Drinks/week | 9 Drinks/week | 8 Drinks/week |
| Body Mass Index | 24.5 kg/m^2 STANDARD_DEVIATION 2.6 | 24.4 kg/m^2 STANDARD_DEVIATION 2.1 | 24.6 kg/m^2 STANDARD_DEVIATION 3 |
| Body Weight | 70.5 kg STANDARD_DEVIATION 9.7 | 70.2 kg STANDARD_DEVIATION 8.2 | 70.7 kg STANDARD_DEVIATION 11.2 |
| Duration of Diabetes Mellitus | 8.2 Years STANDARD_DEVIATION 5.7 | 6.4 Years STANDARD_DEVIATION 5.4 | 9.9 Years STANDARD_DEVIATION 5.5 |
| Height | 169.4 cm STANDARD_DEVIATION 5.3 | 169.5 cm STANDARD_DEVIATION 5.4 | 169.3 cm STANDARD_DEVIATION 5.3 |
| Hemoglobin A1C (HbA1C) | 7.8 % STANDARD_DEVIATION 0.5 | 7.7 % STANDARD_DEVIATION 0.5 | 7.9 % STANDARD_DEVIATION 0.6 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 51 Participants | 26 Participants | 25 Participants |
| Smoking Status Current Smoker | 17 Participants | 8 Participants | 9 Participants |
| Smoking Status Ex-Smoker | 20 Participants | 10 Participants | 10 Participants |
| Smoking Status Never Smoked | 15 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 26 | 10 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 |
Outcome results
Primary
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.
Time frame: Baseline (Day -2) and Day 13
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 50 mg | Change From Baseline in Mean Amplitude of Glycemic Excursions (MAGE) at Day 13 | -18.5 mg/dL |
| Glibenclamide 2.50 mg TDD | Change From Baseline in Mean Amplitude of Glycemic Excursions (MAGE) at Day 13 | -9.7 mg/dL |
Comparison: The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.24595% CI: [-23.8, 6.2]constrained longitudinal analysis model
Secondary
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.
Time frame: Baseline (Day -2) and Day 13
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 50 mg | Change From Baseline in 24-hour Mean Glucose Level | -19.1 mg/dL |
| Glibenclamide 2.50 mg TDD | Change From Baseline in 24-hour Mean Glucose Level | -34.8 mg/dL |
Comparison: The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.0295% CI: [2.5, 28.8]constrained longitudinal analysis model
Secondary
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.
Time frame: Baseline (Day -2) and Day 13
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Sitagliptin 50 mg | Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | Breakfast | -24.8 mg/dL |
| Sitagliptin 50 mg | Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | Lunch | -13.2 mg/dL |
| Sitagliptin 50 mg | Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | Dinner | -9.0 mg/dL |
| Glibenclamide 2.50 mg TDD | Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | Breakfast | -12.0 mg/dL |
| Glibenclamide 2.50 mg TDD | Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | Lunch | 1.2 mg/dL |
| Glibenclamide 2.50 mg TDD | Change From Baseline in Maximum Incremental Postprandial Glucose Levels in Each Meal | Dinner | -14.1 mg/dL |
Comparison: Comparison: Change from Baseline in Maximum Incremental Postprandial Glucose Levels at Breakfast. The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.04195% CI: [-25.1, -0.5]constrained longitudinal analysis model
Comparison: Comparison: Change from Baseline in Maximum Incremental Postprandial Glucose Levels at Lunch. The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.04395% CI: [-28.1, -0.5]constrained longitudinal analysis model
Comparison: Comparison: Change from Baseline in Maximum Incremental Postprandial Glucose Levels at Dinner. The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.50995% CI: [-10.3, 20.4]constrained longitudinal analysis model
Secondary
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.
Time frame: Baseline (Day -2) and Day 13
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Sitagliptin 50 mg | Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | <70 mg/dL | -0.3 Percent change |
| Sitagliptin 50 mg | Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | <60 mg/dL | -0.4 Percent change |
| Sitagliptin 50 mg | Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | <50 mg/dL | -0.3 Percent change |
| Glibenclamide 2.50 mg TDD | Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | <70 mg/dL | 0.8 Percent change |
| Glibenclamide 2.50 mg TDD | Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | <60 mg/dL | 0.2 Percent change |
| Glibenclamide 2.50 mg TDD | Change From Baseline in Percentage of Hypoglycemic Values (Glucose Sensor Readings: < 70, <60, <50 mg/dL) | <50 mg/dL | -0.3 Percent change |
Comparison: Comparison: Change in Baseline in Percentage of Hypoglycemic Values \< 70 mg/dL. The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.13495% CI: [-2.5, 0.3]constrained longitudinal analysis model
Comparison: Comparison: Change in Baseline in Percentage of Hypoglycemic Values \< 60 mg/dL. The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.22695% CI: [-1.5, 0.4]constrained longitudinal analysis model
Comparison: Comparison: Change in Baseline in Percentage of Hypoglycemic Values \< 50 mg/dL. The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.33295% CI: [-0.1, 0]constrained longitudinal analysis model
Secondary
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.
Time frame: Baseline (Day -2) and Day 13
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 50 mg | Change From Baseline in the Standard Deviation of Blood Glucose Levels | -10.2 mg/dL |
| Glibenclamide 2.50 mg TDD | Change From Baseline in the Standard Deviation of Blood Glucose Levels | -4.2 mg/dL |
Comparison: The comparison was conducted at the α=0.05 (2-sided) significance level.p-value: 0.02995% CI: [-11.3, -0.6]constrained longitudinal analysis model