Study to Assess Safety & Efficacy of Sitagliptin as Initial Oral Therapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants. (MK-0431-083)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01485614
Collaborator
(none)
200
4
91.9
Study Details
Study Description
Brief Summary
The purpose of the study is to assess the safety of the addition of sitagliptin, and its effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this study is that sitagliptin reduces A1C more than placebo after 20 weeks of treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This trial is of approximately 56 weeks in duration, including a screening period of up to 1 week, a 1-week single-blind placebo run-in period, a 20-week placebo-controlled, double blind treatment period [Phase A] and a 34-week double-blind active controlled treatment period [Phase B] during which participants randomized to the placebo arm who have not initiated glycemic rescue therapy with metformin during Phase A will receive metformin (in a blinded manner). A telephone contact will be performed 14 days after the last dose of study medication to assess for any serious adverse events (SAEs).
Participants enrolled in the metformin and placebo/sitagliptin arms prior to implementation of Protocol Amendment 05 completed the study on their original treatment assignments.
EUPASS4468 is a follow-up, non-interventional, observational assessment of safety of participants who participated in the MK-0431-083 study for up to 5 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
200 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control
Actual Study Start Date
:
Feb 10, 2012
Actual Primary Completion Date
:
Oct 9, 2019
Actual Study Completion Date
:
Oct 9, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sitagliptin Participants will receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will continue to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
Drug: Sitagliptin
Sitagliptin 100 mg tablet administered orally once daily
Other Names:
Drug: Placebo to metformin
Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily
Drug: Glycemic Rescue 1
Participants in the sitagliptin arm who require glycemic rescue will receive metformin during Weeks 0-20 and Weeks 20-54. Participants in the placebo arm who require glycemic rescue will receive metformin during Weeks 0-20. Participants in the placebo arm who have switched to metformin during Weeks 20-54 and require glycemic rescue will receive sitagliptin.
Biological: Glycemic Rescue 2
Participants who require glycemic rescue after Glycemic Rescue 1 will receive open-label insulin. Participants on background insulin therapy will have the dose of their background insulin up-titrated.
|
| Placebo Comparator: Placebo/Metformin Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
Drug: Metformin
Metformin 500 mg tablets administered orally starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily
Other Names:
Drug: Placebo to sitagliptin
Matching placebo to sitagliptin 100 mg tablet administered orally once daily
Drug: Placebo to metformin
Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily
Drug: Glycemic Rescue 1
Participants in the sitagliptin arm who require glycemic rescue will receive metformin during Weeks 0-20 and Weeks 20-54. Participants in the placebo arm who require glycemic rescue will receive metformin during Weeks 0-20. Participants in the placebo arm who have switched to metformin during Weeks 20-54 and require glycemic rescue will receive sitagliptin.
Biological: Glycemic Rescue 2
Participants who require glycemic rescue after Glycemic Rescue 1 will receive open-label insulin. Participants on background insulin therapy will have the dose of their background insulin up-titrated.
|
| Active Comparator: Metformin Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will continue to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
Drug: Metformin
Metformin 500 mg tablets administered orally starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily
Other Names:
|
| Placebo Comparator: Placebo/Sitagliptin Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
Drug: Sitagliptin
Sitagliptin 100 mg tablet administered orally once daily
Other Names:
Drug: Placebo to sitagliptin
Matching placebo to sitagliptin 100 mg tablet administered orally once daily
Drug: Placebo to metformin
Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Hemoglobin A1C (A1C) at Week 20 [Baseline and Week 20]
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C.
- Baseline Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm [Baseline]
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes.
- Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) [Baseline and Week 20]
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C from a longitudinal data analysis (LDA) model. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The Statistical Analysis Plan (SAP) did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
- Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 [Up to Week 56]
The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
- Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) [Up to Week 56]
The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
- Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 [Up to Week 54]
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
- Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) [Up to Week 54]
The percentage of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
Secondary Outcome Measures
- Change From Baseline in A1C at Week 54 [Baseline and Week 54]
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. This change from baseline reflects the Week 54 A1C minus the Week 0 A1C.
- Percentage of Participants With A1C at Goal (<7.0%) at Week 20 [Week 20]
The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
- Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) [Week 20]
The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
- Percentage of Participants With A1C at Goal (<6.5%) at Week 20 [Week 20]
The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
- Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) [Week 20]
The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
- Percentage of Participants With A1C at Goal (<7.0%) at Week 54 [Week 54]
The percentage of participants with A1C at goal (<7.0%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
- Percentage of Participants With A1C at Goal (<6.5%) at Week 54 [Week 54]
The percentage of participants with A1C at goal (<6.5%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal).
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 [Baseline and Week 20]
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline.
- Baseline Fasting Plasma Glucose (FPG) for the Placebo (Pooled) Arm [Baseline]
Blood glucose was measured on a fasting basis. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes.
- Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) [Baseline and Week 20]
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline and was estimated from a longitudinal data analysis model. The current outcome measure focused on results from participants randomized to sitagliptin or placebo. The Week 20 treatment comparison of Sitagliptin vs Placebo included all participants treated with Sitagliptin or Placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
- Change From Baseline in FPG at Week 54 [Baseline and Week 54]
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 54 minus FPG at baseline.
- Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20 [Baseline and Week 20]
PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour PMG minus the Week 0 2-hour PMG.
- Change From Baseline in 2-hour PMG at Week 54 [Baseline and Week 54]
PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour PMG minus the Week 0 2-hour PMG.
- Change From Baseline in 2-hour Incremental PMG at Week 20 [Baseline and Week 20]
2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour incremental PMG minus the Week 0 2-hour incremental PMG.
- Change From Baseline in 2-Hour Incremental PMG at Week 54 [Baseline and Week 54]
2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour incremental PMG minus the Week 0 2-hour incremental PMG.
- Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin [Baseline and Week 20]
This change from baseline reflects the Week 20 insulin minus the Week 0 insulin.
- Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin [Baseline and Week 54]
This change from baseline reflects the Week 54 insulin minus the Week 0 insulin.
- Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin [Baseline and Week 20]
This change from baseline reflects the Week 20 proinsulin minus the Week 0 proinsulin.
- Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin [Baseline and Week 54]
This change from baseline reflects the Week 54 proinsulin minus the Week 0 proinsulin.
- Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin [Baseline and Week 20]
Change from baseline was the Week 20 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.
- Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin [Baseline and Week 54]
The change from baseline was Week 54 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.
- Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin [Baseline and Week 20]
HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. The change from baseline was Week 20 HOMA-β minus the Week 0 HOMA-β.
- Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin [Baseline and Week 54]
HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. This change from baseline was Week 54 HOMA-β minus the Week 0 HOMA-β.
- Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin [Baseline and Week 20]
HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 20 HOMA-IR minus the Week 0 HOMA-IR.
- Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin [Baseline and Week 54]
HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 54 HOMA-IR minus the Week 0 HOMA-IR.
- Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC.
- Change From Baseline in Insulin 3-hour AUC at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC.
- Change From Baseline in C-peptide 3-Hour AUC at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC.
- Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin total AUC/glucose total AUC ratio minus the Week 0 insulin total AUC/glucose total AUC ratio.
- Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC.
- Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC.
- Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC.
- Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20 [Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio.
- Change From Baseline in Glucose 3-Hour AUC at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC.
- Change From Baseline in Insulin 3-Hour AUC at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC.
- Change From Baseline in C-peptide 3-Hour AUC at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC.
- Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC/glucose 3-hour AUC ratio minus the Week 0 insulin 3-hour AUC/glucose 3-hour AUC ratio.
- Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC.
- Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC.
- Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC.
- Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54 [Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)]
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio.
- Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 [Up to Week 20]
The percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.
- Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54 [Up to Week 54]
The percentage of participants who initiated glycemic rescue therapy prior to Week 54 was reported.
- Change From Baseline in Body Mass Index (BMI) at Week 20 [Baseline and Week 20]
This change from baseline was Week 20 BMI minus the Week 0 BMI.
- Change From Baseline in BMI at Week 54 [Baseline and Week 54]
This change from baseline was Week 54 BMI minus the Week 0 BMI.
- Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20 [Baseline and Week 20]
The percent change from baseline in CD26 = ([CD26 value at Week 20] - [baseline CD26 value]) ÷ baseline CD26 value × 100.
- Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54 [Baseline and Week 54]
The percent change from baseline in CD26 = ([CD26 value at Week 54] - [baseline CD26 value]) ÷ baseline CD26 value × 100.
- Change From Baseline in Calcitonin at Week 20 - Females [Baseline and Week 20]
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin.
- Change From Baseline in Calcitonin at Week 54 - Females [Baseline and Week 54]
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin.
- Change From Baseline in Calcitonin at Week 20 - Males [Baseline and Week 20]
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin.
- Change From Baseline in Calcitonin at Week 54 - Males [Baseline and Week 54]
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin.
- Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females [Baseline and Week 20]
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents
- Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males [Baseline and Week 20]
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents
- Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females [Baseline and Week 54]
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. Bone Collagen Equivalents
- Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males [Baseline and Week 54]
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. All participants in the Metformin arm were missing baseline or Week 54 measurements. BCE = Bone Collagen Equivalents
- Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females [Baseline and Week 20]
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
- Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females [Baseline and Week 54]
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
- Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males [Baseline and Week 20]
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
- Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males [Baseline and Week 54]
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase.
- Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females [Baseline and Week 20]
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
- Percent Change From Baseline in IGF-1 at Week 54 - Females [Baseline and Week 54]
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
- Percent Change From Baseline in IGF-1 at Week 20 - Males [Baseline and Week 20]
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
- Percent Change From Baseline in IGF-1 at Week 54 - Males [Baseline and Week 54]
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100.
- Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females [Baseline and Week 20]
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
- Percent Change From Baseline in IGF-BP3 at Week 54 - Females [Baseline and Week 54]
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
- Percent Change From Baseline in IGF-BP3 at Week 20 - Males [Baseline and Week 20]
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
- Percent Change From Baseline in IGF-BP3 at Week 54 - Males [Baseline and Week 54]
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100.
- Growth Velocity at Week 20 - Females [Week 20]
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
- Growth Velocity at Week 54 - Females [Week 54]
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
- Growth Velocity at Week 20 - Males [Week 20]
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
- Growth Velocity at Week 54 - Males [Week 54]
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
- Skeletal Maturation at Week 20 - Females [Week 20]
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from an X-ray of left hand and wrist.
- Skeletal Maturation at Week 54 - Females [Week 54]
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Placebo/Sitagliptin arm were missing baseline or Week 54 measurements.
- Skeletal Maturation at Week 20 - Males [Week 20]
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist.
- Skeletal Maturation at Week 54 - Males [Week 54]
Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Metformin and Placebo/Sitagliptin arms were missing baseline or Week 54 measurements.
- Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males [Baseline and Week 20]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 20 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia.
- Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males [Baseline and Week 54]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 54 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. All participants in the Metformin arm were missing baseline or Week 54 measurements.
- Change From Baseline in Tanner Staging for Breasts at Week 20 - Females [Baseline and Week 20]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 20 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts.
- Change From Baseline in Tanner Staging for Breasts at Week 54 - Females [Baseline and Week 54]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 54 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts.
- Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females [Baseline and Week 20]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
- Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females [Baseline and Week 54]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
- Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males [Baseline and Week 20]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
- Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males [Baseline and Week 54]
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair.
- Participants With Worsening in Dental Status at Week 20 [Week 20]
Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 20 dental assessments versus baseline dental assessments.
- Participants With Worsening in Dental Status at Week 54 [Week 54]
Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 54 dental assessments versus baseline dental assessments.
Eligibility Criteria
Criteria
Ages Eligible for Study:
10 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Type 2 Diabetes Mellitus (T2DM)
-
Has not received treatment with an antihyperglycemic agent (AHA) for ≥12 weeks prior to the Screening Visit/Visit 1, or is on a stable dose of insulin (without any other AHA) for at least 12 weeks prior to the Screening Visit/Visit 1. At screening, participants on insulin doses that are not stable can have their insulin doses adjusted and be eligible to participate after their dose remains stable for ≥12 weeks, if they meet all other eligibility criteria. In India, only participants on stable doses of insulin will be eligible.
-
An A1C of ≥6.5% and ≤10.0% (For participants on insulin: an A1C ≥7.0% and ≤10.0%).
Exclusion Criteria:
-
History of type 1 diabetes mellitus, autoimmune diabetes mellitus or has a positive antibody screen for anti-GAD (Glutamic Acid Decarboxylase) or (Islet cell autoantigen) ICA-512.
-
Known monogenic diabetes, secondary diabetes, or a genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
-
Symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive test for ketonemia requiring immediate initiation of antihyperglycemic therapy.
-
Previously taken a DPP-4 (Dipeptidyl peptidase-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or GLP-1 (Glucagon-like peptide-1) receptor agonist (such as exenatide or liraglutide).
-
Hypersensitivity or contraindication (according to the product circular in the country of the investigational site) to metformin.
-
Chronic treatment with a medication known to cause weight gain within 30 days of study start or weight loss or increased blood glucose within 8 weeks of study start or treated with an anti-psychotic within the past 12 weeks.
-
On a weight loss program and not in the maintenance phase or have undergone bariatric surgery within 12 months prior to study start.
-
On or likely to require treatment with ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.
-
Undergone a surgical procedure within the prior 4 weeks or has major surgery planned during the study.
-
History of congenital heart disease or cardiovascular disease other than hypertension.
-
Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
-
Active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).
-
Chronic myopathy, mitochondrial disorder, or a progressive neurological or neuromuscular disorder (e.g., polymyositis, or multiple sclerosis).
-
Human immunodeficiency virus (HIV) as assessed by medical history.
-
Clinically significant hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndrome).
-
Under treatment for hyperthyroidism.
-
Exhibits abnormal growth patterns or is being treated with growth hormone.
-
History of malignancy or clinically important hematologic disorder.
-
History of idiopathic acute pancreatitis or chronic pancreatitis.
-
Known history of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year).
-
Donated blood products or has had phlebotomy of >10% of estimated total blood volume within 8 weeks of signing informed consent, or intends to donate blood products or receive blood products within the projected duration of the study.
-
Pregnant, has a positive urine pregnancy test at Screening Visit/Visit 1, is expecting to conceive within the projected duration of the study, or is breast-feeding.
-
Exclusionary laboratory values.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01485614
Other Study ID Numbers:
- 0431-083
- 2011-002528-42
- MK-0431-083
First Posted:
Dec 5, 2011
Last Update Posted:
May 10, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study recruited participants in clinics/clinical offices in 42 countries. |
|---|---|
| Pre-assignment Detail | Participants in a one-week, run-in received sitagliptin placebo prior to morning meals and metformin placebo prior to morning and evening meals. Participants enrolled in the metformin and placebo/sitagliptin arms prior to implementation of Protocol Amendment 05 completed the study on their original treatment assignments. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Period Title: Randomization | ||||
| STARTED | 96 | 90 | 9 | 5 |
| COMPLETED | 95 | 90 | 9 | 5 |
| NOT COMPLETED | 1 | 0 | 0 | 0 |
| Period Title: Randomization | ||||
| STARTED | 95 | 90 | 9 | 5 |
| Treated | 95 | 90 | 9 | 5 |
| COMPLETED | 85 | 86 | 8 | 5 |
| NOT COMPLETED | 10 | 4 | 1 | 0 |
| Period Title: Randomization | ||||
| STARTED | 85 | 86 | 8 | 5 |
| COMPLETED | 74 | 78 | 6 | 5 |
| NOT COMPLETED | 11 | 8 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Total of all reporting groups |
| Overall Participants | 95 | 90 | 9 | 5 | 199 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
14.3
(2.0)
|
13.7
(1.9)
|
13.3
(3.0)
|
15.0
(1.6)
|
14.0
(2.0)
|
| Age, Customized (Count of Participants) | |||||
| In utero |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Preterm newborn infants (gestational age < 37 wks) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Newborns (0-27 days) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Infants and toddlers (28 days-23 months) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Children (2-11 years) |
11
11.6%
|
11
12.2%
|
3
33.3%
|
0
0%
|
25
12.6%
|
| Adolescents (12-17 years) |
84
88.4%
|
79
87.8%
|
6
66.7%
|
5
100%
|
174
87.4%
|
| Adults (18-64 years) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| From 65-84 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 85 years and over |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
54
56.8%
|
58
64.4%
|
6
66.7%
|
3
60%
|
121
60.8%
|
| Male |
41
43.2%
|
32
35.6%
|
3
33.3%
|
2
40%
|
78
39.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
36
37.9%
|
33
36.7%
|
2
22.2%
|
2
40%
|
73
36.7%
|
| Not Hispanic or Latino |
53
55.8%
|
54
60%
|
5
55.6%
|
3
60%
|
115
57.8%
|
| Unknown or Not Reported |
6
6.3%
|
3
3.3%
|
2
22.2%
|
0
0%
|
11
5.5%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
6
6.3%
|
9
10%
|
0
0%
|
0
0%
|
15
7.5%
|
| Asian |
13
13.7%
|
14
15.6%
|
1
11.1%
|
2
40%
|
30
15.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
8
8.4%
|
2
2.2%
|
1
11.1%
|
0
0%
|
11
5.5%
|
| White |
48
50.5%
|
47
52.2%
|
6
66.7%
|
3
60%
|
104
52.3%
|
| More than one race |
20
21.1%
|
18
20%
|
1
11.1%
|
0
0%
|
39
19.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Glycated Hemoglobin (A1C) (Percentage) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Percentage] |
7.43
(1.02)
|
7.56
(1.08)
|
7.43
(1.07)
|
8.02
(0.75)
|
7.50
(1.04)
|
| Fasting Plasma Glucose (mg/dL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mg/dL] |
138.4
(47.2)
|
138.6
(42.8)
|
134.6
(59.1)
|
142.2
(38.7)
|
138.6
(44.7)
|
Outcome Measures
| Title | Change From Baseline in Hemoglobin A1C (A1C) at Week 20 |
|---|---|
| Description | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 78 | 70 | 8 | 3 |
| Mean (Standard Deviation) [Percentage] |
-0.13
(1.58)
|
-0.02
(1.45)
|
-1.03
(0.72)
|
0.57
(1.62)
|
| Title | Baseline Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm |
|---|---|
| Description | A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C. |
| Arm/Group Title | Placebo (Pooled) |
|---|---|
| Arm/Group Description | Participants received placebo from Week 0-20. |
| Measure Participants | 95 |
| Mean (Standard Deviation) [Percentage] |
7.58
(1.06)
|
| Title | Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) |
|---|---|
| Description | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C from a longitudinal data analysis (LDA) model. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The Statistical Analysis Plan (SAP) did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo (Pooled) |
|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received placebo from Week 0-20. |
| Measure Participants | 95 | 95 |
| Least Squares Mean (95% Confidence Interval) [Percentage] |
-0.01
|
0.18
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Placebo/Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.448 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The Least Squares (LS) Mean for the arm "Sitagliptin" is compared against that of "Placebo (pooled)". | |
| Method of Estimation | Estimation Parameter | Least Squares Means Difference |
| Estimated Value | -0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to 0.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 |
|---|---|
| Description | The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Time Frame | Up to Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Count of Participants [Participants] |
73
76.8%
|
67
74.4%
|
7
77.8%
|
4
80%
|
| Title | Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) |
|---|---|
| Description | The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. |
| Time Frame | Up to Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all randomized participants who received ≥1 dose of study medication. Participants (n=5) from the Placebo/Sitagliptin arm were excluded because sitagliptin received during Week 0-54 was an inappropriate control for the Sitagliptin arm which received sitagliptin during both study treatment phases. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin |
|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 95 | 90 |
| Number [Percentage of participants] |
76.8
80.8%
|
74.4
82.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Placebo/Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 2.4 | |
| Confidence Interval |
(2-Sided) 95% -10.0 to 14.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 |
|---|---|
| Description | The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Time Frame | Up to Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Count of Participants [Participants] |
5
5.3%
|
1
1.1%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) |
|---|---|
| Description | The percentage of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. |
| Time Frame | Up to Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all randomized participants who received ≥1 dose of study medication. Participants (n=5) from the Placebo/Sitagliptin arm were excluded because sitagliptin received during Week 0-54 was an inappropriate control for the Sitagliptin arm which received sitagliptin during both study treatment phases. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin |
|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 95 | 90 |
| Number [Percentage of participants] |
5.3
5.6%
|
1.1
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Placebo/Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 4.2 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 10.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in A1C at Week 54 |
|---|---|
| Description | A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. This change from baseline reflects the Week 54 A1C minus the Week 0 A1C. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who took at least one dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 41 | 48 | 4 | 1 |
| Mean (Standard Deviation) [Percentage] |
-0.19
(1.37)
|
-0.90
(1.41)
|
-0.70
(0.94)
|
-0.50
(NA)
|
| Title | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 |
|---|---|
| Description | The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal). |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Number [Percentage of Participants] |
49.5
52.1%
|
37.8
42%
|
77.8
864.4%
|
20.0
400%
|
| Title | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) |
|---|---|
| Description | The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo (Pooled) |
|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received placebo from Week 0-20. |
| Measure Participants | 95 | 95 |
| Number [Percentage of participants] |
49.5
52.1%
|
36.8
40.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Placebo/Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.374 |
| Comments | Percentage of participants with an A1C goal (7.0%) in the arm "Sitagliptin" was compared against the arm "Placebo (pooled)". | |
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 6.7 | |
| Confidence Interval |
(2-Sided) 95% -8.1 to 21.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method based on the Linear Discriminant Analysis (LDA) model was used to impute whether the participant had met the goal. | |
| Title | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 |
|---|---|
| Description | The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal). |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Number [Percentage of participants] |
30.5
32.1%
|
23.3
25.9%
|
66.7
741.1%
|
20.0
400%
|
| Title | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) |
|---|---|
| Description | The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo (Pooled) |
|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received placebo from Week 0-20. |
| Measure Participants | 95 | 95 |
| Number [Percentage of Participants] |
30.5
32.1%
|
23.2
25.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Placebo/Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.639 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | The percentage of participants with an A1C at the A1C goal (6.5%) in the arm "Sitagliptin" was compared against the arm "Placebo (pooled)". | |
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 3.6 | |
| Confidence Interval |
(2-Sided) 95% -11.6 to 18.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method based on the LDA model was used to impute whether the participant had met the goal. | |
| Title | Percentage of Participants With A1C at Goal (<7.0%) at Week 54 |
|---|---|
| Description | The percentage of participants with A1C at goal (<7.0%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal). |
| Time Frame | Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Number [Percentage of participants] |
28.4
29.9%
|
40.0
44.4%
|
33.3
370%
|
20.0
400%
|
| Title | Percentage of Participants With A1C at Goal (<6.5%) at Week 54 |
|---|---|
| Description | The percentage of participants with A1C at goal (<6.5%) at Week 54 was presented. All numbers shown in each individual treatment arm are based on the observed values (Missing = Not at Goal). |
| Time Frame | Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Number [Percentage of participants] |
20.0
21.1%
|
35.6
39.6%
|
22.2
246.7%
|
20.0
400%
|
| Title | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 |
|---|---|
| Description | Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 81 | 74 | 8 | 3 |
| Mean (Standard Deviation) [mg/dL] |
9.98
(61.86)
|
7.59
(41.11)
|
-19.88
(49.78)
|
57.67
(51.05)
|
| Title | Baseline Fasting Plasma Glucose (FPG) for the Placebo (Pooled) Arm |
|---|---|
| Description | Blood glucose was measured on a fasting basis. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at baseline. |
| Arm/Group Title | Placebo (Pooled) |
|---|---|
| Arm/Group Description | Participants received placebo from Week 0-20. |
| Measure Participants | 95 |
| Mean (Standard Deviation) [mg/dL] |
138.8
(42.4)
|
| Title | Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) |
|---|---|
| Description | Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline and was estimated from a longitudinal data analysis model. The current outcome measure focused on results from participants randomized to sitagliptin or placebo. The Week 20 treatment comparison of Sitagliptin vs Placebo included all participants treated with Sitagliptin or Placebo. The Placebo arm in this comparison was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population includes all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo (Pooled) |
|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received placebo from Week 0-20. |
| Measure Participants | 95 | 95 |
| Least Squares Mean (95% Confidence Interval) [mg/dL] |
7.2
|
5.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sitagliptin, Placebo/Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.849 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | The Least Squares (LS) Mean for the arm "Sitagliptin" was compared against that of "Placebo (pooled)". | |
| Method of Estimation | Estimation Parameter | Least Squares Means Difference |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% -14.4 to 17.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in FPG at Week 54 |
|---|---|
| Description | Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 54 minus FPG at baseline. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 44 | 51 | 6 | 1 |
| Mean (Standard Deviation) [mg/dL] |
-3.03
(48.55)
|
-4.52
(50.68)
|
-29.92
(53.19)
|
3.00
(NA)
|
| Title | Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20 |
|---|---|
| Description | PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour PMG minus the Week 0 2-hour PMG. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 4 | 2 |
| Mean (Standard Deviation) [mg/dL] |
-2.9
(42.6)
|
2.1
(72.1)
|
-6.8
(21.1)
|
63.5
(171.8)
|
| Title | Change From Baseline in 2-hour PMG at Week 54 |
|---|---|
| Description | PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour PMG minus the Week 0 2-hour PMG. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 3 | 1 |
| Mean (Standard Deviation) [mg/dL] |
-1.7
(21.3)
|
-16.8
(48.9)
|
-39.7
(32.3)
|
-28.0
(NA)
|
| Title | Change From Baseline in 2-hour Incremental PMG at Week 20 |
|---|---|
| Description | 2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour incremental PMG minus the Week 0 2-hour incremental PMG. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 4 | 2 |
| Mean (Standard Deviation) [mg/dL] |
1.5
(55.3)
|
0.7
(35.9)
|
0.8
(15.6)
|
12.5
(98.3)
|
| Title | Change From Baseline in 2-Hour Incremental PMG at Week 54 |
|---|---|
| Description | 2-Hour incremental PMG = Glucose at 120 minutes - glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour incremental PMG minus the Week 0 2-hour incremental PMG. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 3 | 1 |
| Mean (Standard Deviation) [mg/dL] |
-0.6
(64.6)
|
-26.6
(39.0)
|
-31.3
(34.8)
|
-32.0
(NA)
|
| Title | Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin |
|---|---|
| Description | This change from baseline reflects the Week 20 insulin minus the Week 0 insulin. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 67 | 58 | 7 | 3 |
| Mean (Standard Deviation) [mIU/L] |
1.59
(47.24)
|
-3.91
(22.31)
|
-7.25
(60.58)
|
-1.23
(20.55)
|
| Title | Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin |
|---|---|
| Description | This change from baseline reflects the Week 54 insulin minus the Week 0 insulin. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 37 | 45 | 5 | 1 |
| Mean (Standard Deviation) [mIU/L] |
-9.65
(40.82)
|
-6.64
(32.01)
|
-20.50
(65.08)
|
-9.95
(NA)
|
| Title | Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin |
|---|---|
| Description | This change from baseline reflects the Week 20 proinsulin minus the Week 0 proinsulin. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 68 | 57 | 7 | 3 |
| Mean (Standard Deviation) [pmol/L] |
0.91
(81.88)
|
-10.88
(55.12)
|
12.57
(36.98)
|
-1.33
(9.07)
|
| Title | Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin |
|---|---|
| Description | This change from baseline reflects the Week 54 proinsulin minus the Week 0 proinsulin. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 38 | 42 | 5 | 1 |
| Mean (Standard Deviation) [pmol/L] |
-10.62
(67.54)
|
-16.13
(81.52)
|
-23.30
(42.36)
|
-0.50
(NA)
|
| Title | Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin |
|---|---|
| Description | Change from baseline was the Week 20 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 65 | 55 | 6 | 3 |
| Mean (Standard Deviation) [Ratio] |
0.02
(0.22)
|
0.02
(0.16)
|
-0.03
(0.10)
|
-0.19
(0.45)
|
| Title | Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin |
|---|---|
| Description | The change from baseline was Week 54 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 36 | 41 | 5 | 1 |
| Mean (Standard Deviation) [Ratio] |
0.02
(0.23)
|
-0.03
(0.19)
|
-0.01
(0.06)
|
0.02
(NA)
|
| Title | Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin |
|---|---|
| Description | HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. The change from baseline was Week 20 HOMA-β minus the Week 0 HOMA-β. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 67 | 58 | 7 | 3 |
| Mean (Standard Deviation) [Percentage of Beta Cell Function] |
15.72
(162.47)
|
-53.23
(296.23)
|
-1757.50
(4765.46)
|
-64.78
(126.65)
|
| Title | Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin |
|---|---|
| Description | HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] - 3.5}. This change from baseline was Week 54 HOMA-β minus the Week 0 HOMA-β. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 36 | 45 | 5 | 1 |
| Mean (Standard Deviation) [Percentage of Beta Cell Function] |
-41.15
(183.17)
|
-63.88
(339.74)
|
-1860.69
(4099.22)
|
-121.48
(NA)
|
| Title | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin |
|---|---|
| Description | HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 20 HOMA-IR minus the Week 0 HOMA-IR. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 67 | 58 | 7 | 3 |
| Mean (Standard Deviation) [Index of insulin resistance] |
-0.50
(31.62)
|
-0.86
(9.02)
|
-4.46
(34.65)
|
2.58
(9.30)
|
| Title | Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin |
|---|---|
| Description | HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 54 HOMA-IR minus the Week 0 HOMA-IR. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 36 | 45 | 5 | 1 |
| Mean (Standard Deviation) [Index of insulin resistance] |
-6.13
(34.86)
|
-1.30
(15.31)
|
-15.18
(36.41)
|
-2.21
(NA)
|
| Title | Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 4 | 2 |
| Mean (Standard Deviation) [mg*hr/dL] |
-49.3
(103.6)
|
2.0
(190.0)
|
18.6
(50.9)
|
191.0
(434.2)
|
| Title | Change From Baseline in Insulin 3-hour AUC at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 2 | 2 |
| Mean (Standard Deviation) [µIU*hr/mL] |
-14.5
(128.0)
|
-32.8
(99.9)
|
141.7
(206.1)
|
-145.6
(180.6)
|
| Title | Change From Baseline in C-peptide 3-Hour AUC at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 2 | 2 |
| Mean (Standard Deviation) [ng*hr/mL] |
-1.8
(4.9)
|
-0.1
(3.3)
|
5.9
(7.6)
|
-6.4
(7.1)
|
| Title | Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin total AUC/glucose total AUC ratio minus the Week 0 insulin total AUC/glucose total AUC ratio. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 2 | 2 |
| Mean (Standard Deviation) [[µIU*hr/mL]/[mg*hr/dL]] |
0.0
(0.3)
|
-0.1
(0.3)
|
0.2
(0.4)
|
-0.2
(0.3)
|
| Title | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 4 | 2 |
| Mean (Standard Deviation) [mg*hr/dL] |
-43.5
(97.4)
|
10.8
(58.6)
|
39.8
(50.1)
|
46.2
(201.9)
|
| Title | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 2 | 2 |
| Mean (Standard Deviation) [µIU*hr/mL] |
-12.4
(89.4)
|
-19.4
(93.6)
|
87.5
(124.5)
|
-82.8
(93.4)
|
| Title | Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 12 | 12 | 2 | 2 |
| Mean (Standard Deviation) [ng*hr/ml] |
-1.1
(3.1)
|
-0.4
(4.4)
|
4.1
(5.6)
|
-4.8
(5.2)
|
| Title | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio. |
| Time Frame | Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 11 | 10 | 2 | 2 |
| Mean (Standard Deviation) [[μIU*hr/mL]/[mg*hr/dL]] |
2.2
(9.6)
|
7.2
(17.5)
|
-2.5
(3.2)
|
1.4
(2.2)
|
| Title | Change From Baseline in Glucose 3-Hour AUC at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 3 | 1 |
| Mean (Standard Deviation) [mg*hr/dL] |
-21.1
(47.7)
|
-36.0
(136.1)
|
-73.1
(95.8)
|
-63.3
(NA)
|
| Title | Change From Baseline in Insulin 3-Hour AUC at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 2 | 1 |
| Mean (Standard Deviation) [µIU*hr/mL] |
-43.2
(259.8)
|
-253.9
(282.7)
|
-37.8
(9.4)
|
-184.4
(NA)
|
| Title | Change From Baseline in C-peptide 3-Hour AUC at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 2 | 1 |
| Mean (Standard Deviation) [ng*hr/ml] |
-0.1
(5.7)
|
-6.1
(8.2)
|
1.7
(1.0)
|
-8.9
(NA)
|
| Title | Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC/glucose 3-hour AUC ratio minus the Week 0 insulin 3-hour AUC/glucose 3-hour AUC ratio. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 2 | 1 |
| Mean (Standard Deviation) [[μIU*hr/mL]/[mg*hr/dL]] |
-0.1
(0.5)
|
-0.6
(0.8)
|
-0.0
(0.2)
|
-0.3
(NA)
|
| Title | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 3 | 1 |
| Mean (Standard Deviation) [mg*hr/dL] |
-30.7
(100.7)
|
-50.1
(79.5)
|
-49.0
(87.5)
|
-74.0
(NA)
|
| Title | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 2 | 1 |
| Mean (Standard Deviation) [µIU*hr/mL] |
-103.8
(151.0)
|
-198.5
(263.0)
|
-40.2
(11.5)
|
-116.6
(NA)
|
| Title | Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 8 | 2 | 1 |
| Mean (Standard Deviation) [ng*hr/ml] |
-1.8
(3.0)
|
-5.2
(8.8)
|
0.9
(0.5)
|
-5.9
(NA)
|
| Title | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54 |
|---|---|
| Description | AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio. |
| Time Frame | Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 7 | 6 | 2 | 1 |
| Mean (Standard Deviation) [[µIU*hr/mL]/[mg*hr/dL]] |
4.1
(13.1)
|
3.7
(5.6)
|
-2.7
(4.3)
|
1.4
(NA)
|
| Title | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 |
|---|---|
| Description | The percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported. |
| Time Frame | Up to Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Number [Percentage of participants] |
5.3
5.6%
|
11.1
12.3%
|
0.0
0%
|
40.0
800%
|
| Title | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54 |
|---|---|
| Description | The percentage of participants who initiated glycemic rescue therapy prior to Week 54 was reported. |
| Time Frame | Up to Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 95 | 90 | 9 | 5 |
| Number [Percentage of participants] |
35.8
37.7%
|
28.9
32.1%
|
11.1
123.3%
|
80.0
1600%
|
| Title | Change From Baseline in Body Mass Index (BMI) at Week 20 |
|---|---|
| Description | This change from baseline was Week 20 BMI minus the Week 0 BMI. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 84 | 82 | 8 | 5 |
| Mean (Standard Deviation) [kg/m^2] |
0.0
(2.2)
|
-0.7
(1.9)
|
-0.8
(1.4)
|
-1.7
(2.8)
|
| Title | Change From Baseline in BMI at Week 54 |
|---|---|
| Description | This change from baseline was Week 54 BMI minus the Week 0 BMI. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 72 | 73 | 6 | 5 |
| Mean (Standard Deviation) [kg/m^2] |
-0.4
(2.9)
|
-1.0
(2.9)
|
-0.6
(1.3)
|
-0.3
(1.6)
|
| Title | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20 |
|---|---|
| Description | The percent change from baseline in CD26 = ([CD26 value at Week 20] - [baseline CD26 value]) ÷ baseline CD26 value × 100. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 68 | 57 | 4 | 3 |
| Mean (Standard Deviation) [Percent Change] |
4.06
(19.25)
|
-1.78
(17.18)
|
4.89
(1.90)
|
14.57
(15.46)
|
| Title | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54 |
|---|---|
| Description | The percent change from baseline in CD26 = ([CD26 value at Week 54] - [baseline CD26 value]) ÷ baseline CD26 value × 100. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 56 | 55 | 5 | 3 |
| Mean (Standard Deviation) [Percent Change] |
4.74
(17.18)
|
4.27
(18.24)
|
12.63
(13.02)
|
-5.30
(4.19)
|
| Title | Change From Baseline in Calcitonin at Week 20 - Females |
|---|---|
| Description | Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 43 | 46 | 4 | 2 |
| Mean (Standard Deviation) [ng/L] |
-0.1
(0.5)
|
-2.0
(11.7)
|
0.0
(0.0)
|
0.0
(0.0)
|
| Title | Change From Baseline in Calcitonin at Week 54 - Females |
|---|---|
| Description | Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 30 | 43 | 3 | 2 |
| Mean (Standard Deviation) [ng/L] |
-1.0
(0.6)
|
-1.9
(12.1)
|
0.0
(0.0)
|
0.3
(0.4)
|
| Title | Change From Baseline in Calcitonin at Week 20 - Males |
|---|---|
| Description | Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 35 | 25 | 2 | 2 |
| Mean (Standard Deviation) [ng/L] |
0.2
(1.4)
|
-0.2
(0.6)
|
-1.6
(2.2)
|
0.5
(0.6)
|
| Title | Change From Baseline in Calcitonin at Week 54 - Males |
|---|---|
| Description | Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 33 | 21 | 1 | 2 |
| Mean (Standard Deviation) [ng/L] |
0.1
(1.1)
|
-0.3
(0.9)
|
0.0
(NA)
|
1.4
(0.3)
|
| Title | Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females |
|---|---|
| Description | Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 33 | 31 | 4 | 3 |
| Mean (Standard Deviation) [nmol(BCE)/mmol(creatinine)] |
-28.7
(120.9)
|
-41.2
(148.9)
|
-98.0
(153.0)
|
12.7
(29.2)
|
| Title | Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males |
|---|---|
| Description | Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. BCE = Bone Collagen Equivalents |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 31 | 21 | 1 | 2 |
| Mean (Standard Deviation) [nmol(BCE)/mmol(creatinine)] |
-30.9
(167.2)
|
-69.8
(162.1)
|
62.0
(NA)
|
-29.0
(32.5)
|
| Title | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females |
|---|---|
| Description | Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. Bone Collagen Equivalents |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 28 | 30 | 4 | 3 |
| Mean (Standard Deviation) [nmol(BCE)/mmol(creatinine)] |
-88.4
(102.6)
|
-61.2
(137.6)
|
-80.3
(208.5)
|
-17.0
(13.5)
|
| Title | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males |
|---|---|
| Description | Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. All participants in the Metformin arm were missing baseline or Week 54 measurements. BCE = Bone Collagen Equivalents |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 30 | 16 | 0 | 1 |
| Mean (Standard Deviation) [nmol(BCE)/mmol(creatinine)] |
-78.2
(166.9)
|
-102.4
(267.7)
|
-30.0
(NA)
|
| Title | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females |
|---|---|
| Description | Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 43 | 52 | 5 | 3 |
| Mean (Standard Deviation) [μg/L] |
-6.0
(13.7)
|
-4.2
(9.9)
|
-9.7
(7.7)
|
10.7
(9.7)
|
| Title | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females |
|---|---|
| Description | Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 30 | 43 | 4 | 3 |
| Mean (Standard Deviation) [μg/L] |
-20.0
(28.4)
|
-13.5
(18.1)
|
-14.9
(10.3)
|
-6.9
(9.2)
|
| Title | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males |
|---|---|
| Description | Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 36 | 25 | 2 | 2 |
| Mean (Standard Deviation) [μg/L] |
-2.2
(21.6)
|
0.1
(19.9)
|
-7.1
(0.2)
|
4.7
(8.2)
|
| Title | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males |
|---|---|
| Description | Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 33 | 20 | 1 | 2 |
| Mean (Standard Deviation) [μg/L] |
-16.2
(28.0)
|
-15.0
(27.0)
|
-1.3
(NA)
|
-15.3
(12.4)
|
| Title | Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females |
|---|---|
| Description | IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 38 | 49 | 5 | 2 |
| Mean (Standard Deviation) [Percent Change] |
0.5
(21.9)
|
11.0
(34.0)
|
-3.2
(14.9)
|
41.4
(31.2)
|
| Title | Percent Change From Baseline in IGF-1 at Week 54 - Females |
|---|---|
| Description | IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 30 | 42 | 4 | 1 |
| Mean (Standard Deviation) [Percent Change] |
-1.5
(34.4)
|
7.2
(57.6)
|
-11.9
(13.4)
|
-13.5
(NA)
|
| Title | Percent Change From Baseline in IGF-1 at Week 20 - Males |
|---|---|
| Description | IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 36 | 20 | 2 | 2 |
| Mean (Standard Deviation) [Percent Change] |
-2.7
(22.1)
|
9.3
(29.6)
|
7.6
(17.4)
|
5.3
(16.2)
|
| Title | Percent Change From Baseline in IGF-1 at Week 54 - Males |
|---|---|
| Description | IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value]) ÷ [baseline IGF-1 value] × 100. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 32 | 18 | 1 | 2 |
| Mean (Standard Deviation) [Percent Change] |
-4.9
(33.5)
|
29.6
(99.8)
|
18.8
(NA)
|
-6.8
(22.1)
|
| Title | Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females |
|---|---|
| Description | IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 41 | 50 | 6 | 2 |
| Mean (Standard Deviation) [Percent Change] |
3.5
(18.2)
|
3.8
(13.8)
|
8.4
(12.9)
|
-0.7
(24.1)
|
| Title | Percent Change From Baseline in IGF-BP3 at Week 54 - Females |
|---|---|
| Description | IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 31 | 45 | 4 | 2 |
| Mean (Standard Deviation) [Percent Change] |
2.0
(16.7)
|
4.5
(17.0)
|
11.4
(17.4)
|
-13.4
(9.9)
|
| Title | Percent Change From Baseline in IGF-BP3 at Week 20 - Males |
|---|---|
| Description | IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 36 | 24 | 2 | 2 |
| Mean (Standard Deviation) [Percent Change] |
5.6
(13.3)
|
10.2
(18.6)
|
3.3
(0.5)
|
14.2
(50.6)
|
| Title | Percent Change From Baseline in IGF-BP3 at Week 54 - Males |
|---|---|
| Description | IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value]) ÷ [baseline IGF-BP3 value] × 100. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 32 | 21 | 1 | 2 |
| Mean (Standard Deviation) [Percent Change] |
5.4
(18.4)
|
18.2
(43.1)
|
-2.9
(NA)
|
22.5
(8.3)
|
| Title | Growth Velocity at Week 20 - Females |
|---|---|
| Description | Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age). |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 46 | 53 | 6 | 3 |
| Mean (Standard Deviation) [cm/year] |
3.2
(8.2)
|
1.9
(2.7)
|
5.0
(6.8)
|
0.6
(1.6)
|
| Title | Growth Velocity at Week 54 - Females |
|---|---|
| Description | Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age). |
| Time Frame | Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 37 | 48 | 5 | 3 |
| Mean (Standard Deviation) [cm/year] |
2.1
(3.7)
|
1.2
(1.8)
|
2.4
(2.9)
|
0.7
(1.0)
|
| Title | Growth Velocity at Week 20 - Males |
|---|---|
| Description | Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age). |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 38 | 29 | 2 | 2 |
| Mean (Standard Deviation) [cm/year] |
2.6
(2.7)
|
3.6
(3.2)
|
-1.0
(1.3)
|
1.7
(2.4)
|
| Title | Growth Velocity at Week 54 - Males |
|---|---|
| Description | Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age). |
| Time Frame | Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 35 | 25 | 1 | 2 |
| Mean (Standard Deviation) [cm/year] |
2.5
(2.5)
|
2.8
(2.1)
|
1.7
(NA)
|
2.8
(4.0)
|
| Title | Skeletal Maturation at Week 20 - Females |
|---|---|
| Description | Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from an X-ray of left hand and wrist. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 17 | 18 | 3 | 2 |
| Mean (Standard Deviation) [Ratio] |
0.6
(1.9)
|
0.4
(1.8)
|
1.7
(2.3)
|
-0.8
(5.5)
|
| Title | Skeletal Maturation at Week 54 - Females |
|---|---|
| Description | Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Placebo/Sitagliptin arm were missing baseline or Week 54 measurements. |
| Time Frame | Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 8 | 14 | 3 | 0 |
| Mean (Standard Deviation) [Ratio] |
1.3
(1.1)
|
1.0
(0.6)
|
1.3
(2.2)
|
| Title | Skeletal Maturation at Week 20 - Males |
|---|---|
| Description | Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 13 | 17 | 1 | 1 |
| Mean (Standard Deviation) [Ratio] |
1.6
(1.7)
|
1.2
(1.1)
|
0.4
(NA)
|
2.4
(NA)
|
| Title | Skeletal Maturation at Week 54 - Males |
|---|---|
| Description | Skeletal Maturation = (Change from Baseline in bone age)/(Change from Baseline in chronologic age). Bone age was determined from X-ray of left hand and wrist. All participants in the Metformin and Placebo/Sitagliptin arms were missing baseline or Week 54 measurements. |
| Time Frame | Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 11 | 10 | 0 | 0 |
| Mean (Standard Deviation) [Ratio] |
1.3
(0.9)
|
1.3
(0.6)
|
| Title | Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 20 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 31 | 29 | 1 | 2 |
| Mean (Standard Deviation) [Score on a scale] |
0.3
(0.5)
|
0.2
(0.4)
|
0.0
(NA)
|
0.5
(0.7)
|
| Title | Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 54 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. All participants in the Metformin arm were missing baseline or Week 54 measurements. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 26 | 23 | 0 | 2 |
| Mean (Standard Deviation) [Score on a scale] |
0.5
(0.6)
|
0.6
(0.7)
|
0.6
(0.7)
|
| Title | Change From Baseline in Tanner Staging for Breasts at Week 20 - Females |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 20 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 38 | 44 | 5 | 3 |
| Mean (Standard Deviation) [Score on a Scale] |
0.2
(0.6)
|
0.1
(0.3)
|
0.2
(0.4)
|
0.3
(0.6)
|
| Title | Change From Baseline in Tanner Staging for Breasts at Week 54 - Females |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 54 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 28 | 36 | 4 | 3 |
| Mean (Standard Deviation) [Score on a Scale] |
0.5
(0.7)
|
0.4
(0.6)
|
0.5
(1.0)
|
0.7
(0.6)
|
| Title | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 38 | 43 | 5 | 3 |
| Mean (Standard Deviation) [Score on a scale] |
0.1
(0.4)
|
0.1
(0.3)
|
0.2
(0.4)
|
0.0
(0.0)
|
| Title | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development (females). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 28 | 35 | 4 | 3 |
| Mean (Standard Deviation) [Score on a scale] |
0.5
(0.6)
|
0.3
(0.5)
|
0.8
(1.5)
|
0.3
(0.6)
|
| Title | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. |
| Time Frame | Baseline and Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 32 | 29 | 1 | 2 |
| Mean (Standard Deviation) [Score on a scale] |
0.3
(0.5)
|
0.2
(0.4)
|
0.0
(NA)
|
0.5
(0.7)
|
| Title | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males |
|---|---|
| Description | Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development (males). Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. |
| Time Frame | Baseline and Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. Tanner staging results for pubic hair were unavailable for the Metformin arm. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 26 | 23 | 0 | 2 |
| Mean (Standard Deviation) [Score on a scale] |
0.5
(0.7)
|
0.6
(0.5)
|
0.5
(0.7)
|
| Title | Participants With Worsening in Dental Status at Week 20 |
|---|---|
| Description | Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 20 dental assessments versus baseline dental assessments. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had dental data at baseline and Week 20. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. |
| Measure Participants | 88 | 85 | 8 | 5 |
| 1. With ≥1 tooth with worsening in any category |
32
33.7%
|
25
27.8%
|
1
11.1%
|
0
0%
|
| 2. With ≥1 tooth with worsening fracture |
5
5.3%
|
5
5.6%
|
0
0%
|
0
0%
|
| 3. With ≥1 tooth with worsening discoloration |
29
30.5%
|
23
25.6%
|
0
0%
|
0
0%
|
| 4. With ≥1 tooth with worsening enamel defect |
7
7.4%
|
4
4.4%
|
1
11.1%
|
0
0%
|
| Title | Participants With Worsening in Dental Status at Week 54 |
|---|---|
| Description | Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening was defined as worsening of tooth fracture, tooth discoloration, or enamel defect as determined by an independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 54 dental assessments versus baseline dental assessments. |
| Time Frame | Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all randomized participants who received ≥1 dose of study medication and had dental data at baseline and Week 54. |
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Measure Participants | 79 | 78 | 8 | 5 |
| 1. With ≥1 tooth with worsening in any category |
49
51.6%
|
50
55.6%
|
2
22.2%
|
0
0%
|
| 2. With ≥1 tooth with worsening fracture |
13
13.7%
|
15
16.7%
|
1
11.1%
|
0
0%
|
| 3. With ≥1 tooth with worsening discoloration |
45
47.4%
|
48
53.3%
|
2
22.2%
|
0
0%
|
| 4. With ≥1 with worsening enamel defect |
13
13.7%
|
13
14.4%
|
1
11.1%
|
0
0%
|
Adverse Events
| Time Frame | SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received ≥1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the treatment phases of the study, approximately 42 months after randomization. | |||||||
| Arm/Group Title | Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin | ||||
| Arm/Group Description | Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | ||||
All Cause Mortality |
||||||||
| Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/96 (1%) | 0/90 (0%) | 0/9 (0%) | 0/5 (0%) | ||||
Serious Adverse Events |
||||||||
| Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/95 (10.5%) | 7/90 (7.8%) | 1/9 (11.1%) | 3/5 (60%) | ||||
| Gastrointestinal disorders | ||||||||
| Gastritis | 1/95 (1.1%) | 2 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Infections and infestations | ||||||||
| Abscess soft tissue | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Appendicitis | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Dengue fever | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Gastroenteritis viral | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Pneumonia | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Concussion | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Investigations | ||||||||
| Blood glucose increased | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Diabetic ketoacidosis | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Hyperglycaemia | 3/95 (3.2%) | 4 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acute lymphocytic leukaemia | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Leukaemia | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Affect lability | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Nephrolithiasis | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Reproductive system and breast disorders | ||||||||
| Ovarian cyst ruptured | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Erythema nodosum | 0/95 (0%) | 0 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Social circumstances | ||||||||
| Sexual abuse | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Sitagliptin | Placebo/Metformin | Metformin | Placebo/Sitagliptin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 62/95 (65.3%) | 53/90 (58.9%) | 7/9 (77.8%) | 4/5 (80%) | ||||
| Cardiac disorders | ||||||||
| Wandering pacemaker | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Eye disorders | ||||||||
| Blepharitis | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Eye pain | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 8/95 (8.4%) | 10 | 7/90 (7.8%) | 10 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Diarrhoea | 8/95 (8.4%) | 9 | 11/90 (12.2%) | 14 | 2/9 (22.2%) | 2 | 0/5 (0%) | 0 |
| Dyspepsia | 3/95 (3.2%) | 6 | 2/90 (2.2%) | 2 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Nausea | 5/95 (5.3%) | 5 | 4/90 (4.4%) | 5 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Vomiting | 6/95 (6.3%) | 9 | 7/90 (7.8%) | 8 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| General disorders | ||||||||
| Influenza like illness | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 4 | 0/5 (0%) | 0 |
| Pyrexia | 1/95 (1.1%) | 1 | 6/90 (6.7%) | 7 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Infections and infestations | ||||||||
| Anal abscess | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Gastroenteritis | 3/95 (3.2%) | 4 | 7/90 (7.8%) | 10 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Influenza | 2/95 (2.1%) | 2 | 6/90 (6.7%) | 7 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Nasopharyngitis | 15/95 (15.8%) | 19 | 6/90 (6.7%) | 6 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Pertussis | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Pharyngitis | 6/95 (6.3%) | 7 | 6/90 (6.7%) | 6 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Upper respiratory tract infection | 12/95 (12.6%) | 15 | 12/90 (13.3%) | 13 | 1/9 (11.1%) | 1 | 1/5 (20%) | 1 |
| Urinary tract infection | 4/95 (4.2%) | 4 | 9/90 (10%) | 11 | 0/9 (0%) | 0 | 0/5 (0%) | 0 |
| Viral infection | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 4 |
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 1/95 (1.1%) | 1 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Tooth fracture | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 4/95 (4.2%) | 4 | 3/90 (3.3%) | 3 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Hypoglycaemia | 16/95 (16.8%) | 107 | 12/90 (13.3%) | 37 | 3/9 (33.3%) | 65 | 2/5 (40%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 3/95 (3.2%) | 3 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Neck pain | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Pain in extremity | 1/95 (1.1%) | 1 | 1/90 (1.1%) | 1 | 1/9 (11.1%) | 1 | 1/5 (20%) | 1 |
| Nervous system disorders | ||||||||
| Dizziness | 3/95 (3.2%) | 5 | 2/90 (2.2%) | 2 | 0/9 (0%) | 0 | 2/5 (40%) | 4 |
| Headache | 9/95 (9.5%) | 9 | 13/90 (14.4%) | 16 | 2/9 (22.2%) | 5 | 1/5 (20%) | 1 |
| Renal and urinary disorders | ||||||||
| Dysuria | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Nephrolithiasis | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Dysmenorrhoea | 2/95 (2.1%) | 2 | 1/90 (1.1%) | 2 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Gynaecomastia | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Hyperventilation | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Oropharyngeal pain | 2/95 (2.1%) | 2 | 2/90 (2.2%) | 2 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Respiratory disorder | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Rhinorrhoea | 1/95 (1.1%) | 1 | 1/90 (1.1%) | 1 | 0/9 (0%) | 0 | 1/5 (20%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Urticaria | 0/95 (0%) | 0 | 0/90 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypertension | 2/95 (2.1%) | 2 | 2/90 (2.2%) | 2 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/ presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01485614
Other Study ID Numbers:
- 0431-083
- 2011-002528-42
- MK-0431-083
First Posted:
Dec 5, 2011
Last Update Posted:
May 10, 2021
Last Verified:
Apr 1, 2021