Diabetes Mellitus, Type 2 Diabetes
Conditions
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.
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.
Interventions
DRUGSitagliptin
Sitagliptin 100 mg tablet administered orally once daily
DRUGMetformin
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
Matching placebo to sitagliptin 100 mg tablet administered orally once daily
Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily
DRUGGlycemic 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.
BIOLOGICALGlycemic 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.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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 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 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
Participant flow
Recruitment details
The study recruited participants in clinics/clinical offices in 42 countries.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 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. | 95 |
| Placebo/Metformin 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. | 90 |
| Metformin 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. | 9 |
| Placebo/Sitagliptin 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. | 5 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Randomization | Not Treated | 1 | 0 | 0 | 0 |
| Weeks 0-20 | Lost to Follow-up | 2 | 0 | 0 | 0 |
| Weeks 0-20 | Withdrawal by Parent/Guardian | 5 | 2 | 0 | 0 |
| Weeks 0-20 | Withdrawal by Subject | 3 | 2 | 1 | 0 |
| Weeks 20-54 | Lost to Follow-up | 4 | 3 | 1 | 0 |
| Weeks 20-54 | Withdrawal by Parent/Guardian | 2 | 2 | 1 | 0 |
| Weeks 20-54 | Withdrawal by Subject | 5 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo/Sitagliptin | Total | Metformin | Placebo/Metformin | Sitagliptin |
|---|---|---|---|---|---|
| Age, Continuous | 15.0 years STANDARD_DEVIATION 1.6 | 14.0 years STANDARD_DEVIATION 2 | 13.3 years STANDARD_DEVIATION 3 | 13.7 years STANDARD_DEVIATION 1.9 | 14.3 years STANDARD_DEVIATION 2 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 5 Participants | 174 Participants | 6 Participants | 79 Participants | 84 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 25 Participants | 3 Participants | 11 Participants | 11 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 73 Participants | 2 Participants | 33 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 115 Participants | 5 Participants | 54 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 11 Participants | 2 Participants | 3 Participants | 6 Participants |
| Fasting Plasma Glucose | 142.2 mg/dL STANDARD_DEVIATION 38.7 | 138.6 mg/dL STANDARD_DEVIATION 44.7 | 134.6 mg/dL STANDARD_DEVIATION 59.1 | 138.6 mg/dL STANDARD_DEVIATION 42.8 | 138.4 mg/dL STANDARD_DEVIATION 47.2 |
| Glycated Hemoglobin (A1C) | 8.02 Percentage STANDARD_DEVIATION 0.75 | 7.50 Percentage STANDARD_DEVIATION 1.04 | 7.43 Percentage STANDARD_DEVIATION 1.07 | 7.56 Percentage STANDARD_DEVIATION 1.08 | 7.43 Percentage STANDARD_DEVIATION 1.02 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 15 Participants | 0 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 30 Participants | 1 Participants | 14 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 11 Participants | 1 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 39 Participants | 1 Participants | 18 Participants | 20 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 104 Participants | 6 Participants | 47 Participants | 48 Participants |
| Sex: Female, Male Female | 3 Participants | 121 Participants | 6 Participants | 58 Participants | 54 Participants |
| Sex: Female, Male Male | 2 Participants | 78 Participants | 3 Participants | 32 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 96 | 0 / 90 | 0 / 9 | 0 / 5 |
| other Total, other adverse events | 62 / 95 | 53 / 90 | 7 / 9 | 4 / 5 |
| serious Total, serious adverse events | 10 / 95 | 7 / 90 | 1 / 9 | 3 / 5 |
Outcome results
Primary
Baseline Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm
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
Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Glycated Hemoglobin (A1C) for the Placebo (Pooled) Arm | 7.58 Percentage | Standard Deviation 1.06 |
Primary
Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | -0.01 Percentage |
| Placebo/Metformin | Change From Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | 0.18 Percentage |
p-value: =0.44895% CI: [-0.68, 0.3]Mixed Models Analysis
Primary
Change From Baseline in Hemoglobin A1C (A1C) at 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.
Time frame: Baseline and Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Hemoglobin A1C (A1C) at Week 20 | -0.13 Percentage | Standard Deviation 1.58 |
| Placebo/Metformin | Change From Baseline in Hemoglobin A1C (A1C) at Week 20 | -0.02 Percentage | Standard Deviation 1.45 |
| Metformin | Change From Baseline in Hemoglobin A1C (A1C) at Week 20 | -1.03 Percentage | Standard Deviation 0.72 |
| Placebo/Sitagliptin | Change From Baseline in Hemoglobin A1C (A1C) at Week 20 | 0.57 Percentage | Standard Deviation 1.62 |
Primary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54
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.
Time frame: Up to Week 54
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 | 5 Participants |
| Placebo/Metformin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 | 1 Participants |
| Metformin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 | 0 Participants |
| Placebo/Sitagliptin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 | 0 Participants |
Primary
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56
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.
Time frame: Up to Week 56
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 73 Participants |
| Placebo/Metformin | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 67 Participants |
| Metformin | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 7 Participants |
| Placebo/Sitagliptin | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 4 Participants |
Primary
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) | 5.3 Percentage of participants |
| Placebo/Metformin | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) | 1.1 Percentage of participants |
95% CI: [-1.3, 10.8]
Primary
Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin)
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) | 76.8 Percentage of participants |
| Placebo/Metformin | Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) | 74.4 Percentage of participants |
95% CI: [-10, 14.9]
Secondary
Baseline Fasting Plasma Glucose (FPG) for the Placebo (Pooled) Arm
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
Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Fasting Plasma Glucose (FPG) for the Placebo (Pooled) Arm | 138.8 mg/dL | Standard Deviation 42.4 |
Secondary
Change From Baseline in 2-hour Incremental PMG at 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.
Time frame: Baseline and Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in 2-hour Incremental PMG at Week 20 | 1.5 mg/dL | Standard Deviation 55.3 |
| Placebo/Metformin | Change From Baseline in 2-hour Incremental PMG at Week 20 | 0.7 mg/dL | Standard Deviation 35.9 |
| Metformin | Change From Baseline in 2-hour Incremental PMG at Week 20 | 0.8 mg/dL | Standard Deviation 15.6 |
| Placebo/Sitagliptin | Change From Baseline in 2-hour Incremental PMG at Week 20 | 12.5 mg/dL | Standard Deviation 98.3 |
Secondary
Change From Baseline in 2-Hour Incremental PMG at 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.
Time frame: Baseline and Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in 2-Hour Incremental PMG at Week 54 | -0.6 mg/dL | Standard Deviation 64.6 |
| Placebo/Metformin | Change From Baseline in 2-Hour Incremental PMG at Week 54 | -26.6 mg/dL | Standard Deviation 39 |
| Metformin | Change From Baseline in 2-Hour Incremental PMG at Week 54 | -31.3 mg/dL | Standard Deviation 34.8 |
| Placebo/Sitagliptin | Change From Baseline in 2-Hour Incremental PMG at Week 54 | -32.0 mg/dL | — |
Secondary
Change From Baseline in 2-hour PMG at 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.
Time frame: Baseline and Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in 2-hour PMG at Week 54 | -1.7 mg/dL | Standard Deviation 21.3 |
| Placebo/Metformin | Change From Baseline in 2-hour PMG at Week 54 | -16.8 mg/dL | Standard Deviation 48.9 |
| Metformin | Change From Baseline in 2-hour PMG at Week 54 | -39.7 mg/dL | Standard Deviation 32.3 |
| Placebo/Sitagliptin | Change From Baseline in 2-hour PMG at Week 54 | -28.0 mg/dL | — |
Secondary
Change From Baseline in 2-Hour Post-meal Glucose (PMG) at 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.
Time frame: Baseline and Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20 | -2.9 mg/dL | Standard Deviation 42.6 |
| Placebo/Metformin | Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20 | 2.1 mg/dL | Standard Deviation 72.1 |
| Metformin | Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20 | -6.8 mg/dL | Standard Deviation 21.1 |
| Placebo/Sitagliptin | Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20 | 63.5 mg/dL | Standard Deviation 171.8 |
Secondary
Change From Baseline in A1C at 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.
Time frame: Baseline and Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in A1C at Week 54 | -0.19 Percentage | Standard Deviation 1.37 |
| Placebo/Metformin | Change From Baseline in A1C at Week 54 | -0.90 Percentage | Standard Deviation 1.41 |
| Metformin | Change From Baseline in A1C at Week 54 | -0.70 Percentage | Standard Deviation 0.94 |
| Placebo/Sitagliptin | Change From Baseline in A1C at Week 54 | -0.50 Percentage | — |
Secondary
Change From Baseline in BMI at Week 54
This change from baseline was Week 54 BMI minus the Week 0 BMI.
Time frame: Baseline and Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in BMI at Week 54 | -0.4 kg/m^2 | Standard Deviation 2.9 |
| Placebo/Metformin | Change From Baseline in BMI at Week 54 | -1.0 kg/m^2 | Standard Deviation 2.9 |
| Metformin | Change From Baseline in BMI at Week 54 | -0.6 kg/m^2 | Standard Deviation 1.3 |
| Placebo/Sitagliptin | Change From Baseline in BMI at Week 54 | -0.3 kg/m^2 | Standard Deviation 1.6 |
Secondary
Change From Baseline in Body Mass Index (BMI) at Week 20
This change from baseline was Week 20 BMI minus the Week 0 BMI.
Time frame: Baseline and Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Body Mass Index (BMI) at Week 20 | 0.0 kg/m^2 | Standard Deviation 2.2 |
| Placebo/Metformin | Change From Baseline in Body Mass Index (BMI) at Week 20 | -0.7 kg/m^2 | Standard Deviation 1.9 |
| Metformin | Change From Baseline in Body Mass Index (BMI) at Week 20 | -0.8 kg/m^2 | Standard Deviation 1.4 |
| Placebo/Sitagliptin | Change From Baseline in Body Mass Index (BMI) at Week 20 | -1.7 kg/m^2 | Standard Deviation 2.8 |
Secondary
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females | -6.0 μg/L | Standard Deviation 13.7 |
| Placebo/Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females | -4.2 μg/L | Standard Deviation 9.9 |
| Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females | -9.7 μg/L | Standard Deviation 7.7 |
| Placebo/Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females | 10.7 μg/L | Standard Deviation 9.7 |
Secondary
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males | -2.2 μg/L | Standard Deviation 21.6 |
| Placebo/Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males | 0.1 μg/L | Standard Deviation 19.9 |
| Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males | -7.1 μg/L | Standard Deviation 0.2 |
| Placebo/Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Males | 4.7 μg/L | Standard Deviation 8.2 |
Secondary
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females | -20.0 μg/L | Standard Deviation 28.4 |
| Placebo/Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females | -13.5 μg/L | Standard Deviation 18.1 |
| Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females | -14.9 μg/L | Standard Deviation 10.3 |
| Placebo/Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females | -6.9 μg/L | Standard Deviation 9.2 |
Secondary
Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males | -16.2 μg/L | Standard Deviation 28 |
| Placebo/Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males | -15.0 μg/L | Standard Deviation 27 |
| Metformin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males | -1.3 μg/L | — |
| Placebo/Sitagliptin | Change From Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males | -15.3 μg/L | Standard Deviation 12.4 |
Secondary
Change From Baseline in Calcitonin at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Calcitonin at Week 20 - Females | -0.1 ng/L | Standard Deviation 0.5 |
| Placebo/Metformin | Change From Baseline in Calcitonin at Week 20 - Females | -2.0 ng/L | Standard Deviation 11.7 |
| Metformin | Change From Baseline in Calcitonin at Week 20 - Females | 0.0 ng/L | Standard Deviation 0 |
| Placebo/Sitagliptin | Change From Baseline in Calcitonin at Week 20 - Females | 0.0 ng/L | Standard Deviation 0 |
Secondary
Change From Baseline in Calcitonin at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Calcitonin at Week 20 - Males | 0.2 ng/L | Standard Deviation 1.4 |
| Placebo/Metformin | Change From Baseline in Calcitonin at Week 20 - Males | -0.2 ng/L | Standard Deviation 0.6 |
| Metformin | Change From Baseline in Calcitonin at Week 20 - Males | -1.6 ng/L | Standard Deviation 2.2 |
| Placebo/Sitagliptin | Change From Baseline in Calcitonin at Week 20 - Males | 0.5 ng/L | Standard Deviation 0.6 |
Secondary
Change From Baseline in Calcitonin at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Calcitonin at Week 54 - Females | -1.0 ng/L | Standard Deviation 0.6 |
| Placebo/Metformin | Change From Baseline in Calcitonin at Week 54 - Females | -1.9 ng/L | Standard Deviation 12.1 |
| Metformin | Change From Baseline in Calcitonin at Week 54 - Females | 0.0 ng/L | Standard Deviation 0 |
| Placebo/Sitagliptin | Change From Baseline in Calcitonin at Week 54 - Females | 0.3 ng/L | Standard Deviation 0.4 |
Secondary
Change From Baseline in Calcitonin at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Calcitonin at Week 54 - Males | 0.1 ng/L | Standard Deviation 1.1 |
| Placebo/Metformin | Change From Baseline in Calcitonin at Week 54 - Males | -0.3 ng/L | Standard Deviation 0.9 |
| Metformin | Change From Baseline in Calcitonin at Week 54 - Males | 0.0 ng/L | — |
| Placebo/Sitagliptin | Change From Baseline in Calcitonin at Week 54 - Males | 1.4 ng/L | Standard Deviation 0.3 |
Secondary
Change From Baseline in C-peptide 3-Hour AUC at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in C-peptide 3-Hour AUC at Week 20 | -1.8 ng*hr/mL | Standard Deviation 4.9 |
| Placebo/Metformin | Change From Baseline in C-peptide 3-Hour AUC at Week 20 | -0.1 ng*hr/mL | Standard Deviation 3.3 |
| Metformin | Change From Baseline in C-peptide 3-Hour AUC at Week 20 | 5.9 ng*hr/mL | Standard Deviation 7.6 |
| Placebo/Sitagliptin | Change From Baseline in C-peptide 3-Hour AUC at Week 20 | -6.4 ng*hr/mL | Standard Deviation 7.1 |
Secondary
Change From Baseline in C-peptide 3-Hour AUC at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in C-peptide 3-Hour AUC at Week 54 | -0.1 ng*hr/ml | Standard Deviation 5.7 |
| Placebo/Metformin | Change From Baseline in C-peptide 3-Hour AUC at Week 54 | -6.1 ng*hr/ml | Standard Deviation 8.2 |
| Metformin | Change From Baseline in C-peptide 3-Hour AUC at Week 54 | 1.7 ng*hr/ml | Standard Deviation 1 |
| Placebo/Sitagliptin | Change From Baseline in C-peptide 3-Hour AUC at Week 54 | -8.9 ng*hr/ml | — |
Secondary
Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20 | -1.1 ng*hr/ml | Standard Deviation 3.1 |
| Placebo/Metformin | Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20 | -0.4 ng*hr/ml | Standard Deviation 4.4 |
| Metformin | Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20 | 4.1 ng*hr/ml | Standard Deviation 5.6 |
| Placebo/Sitagliptin | Change From Baseline in C-peptide Excursion 3-Hour AUC at Week 20 | -4.8 ng*hr/ml | Standard Deviation 5.2 |
Secondary
Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54 | -1.8 ng*hr/ml | Standard Deviation 3 |
| Placebo/Metformin | Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54 | -5.2 ng*hr/ml | Standard Deviation 8.8 |
| Metformin | Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54 | 0.9 ng*hr/ml | Standard Deviation 0.5 |
| Placebo/Sitagliptin | Change From Baseline in C-Peptide Excursion 3-Hour AUC at Week 54 | -5.9 ng*hr/ml | — |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 | 9.98 mg/dL | Standard Deviation 61.86 |
| Placebo/Metformin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 | 7.59 mg/dL | Standard Deviation 41.11 |
| Metformin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 | -19.88 mg/dL | Standard Deviation 49.78 |
| Placebo/Sitagliptin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 | 57.67 mg/dL | Standard Deviation 51.05 |
Secondary
Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | 7.2 mg/dL |
| Placebo/Metformin | Change From Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | 5.7 mg/dL |
p-value: =0.84995% CI: [-14.4, 17.5]Mixed Models Analysis
Secondary
Change From Baseline in FPG at Week 54
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in FPG at Week 54 | -3.03 mg/dL | Standard Deviation 48.55 |
| Placebo/Metformin | Change From Baseline in FPG at Week 54 | -4.52 mg/dL | Standard Deviation 50.68 |
| Metformin | Change From Baseline in FPG at Week 54 | -29.92 mg/dL | Standard Deviation 53.19 |
| Placebo/Sitagliptin | Change From Baseline in FPG at Week 54 | 3.00 mg/dL | — |
Secondary
Change From Baseline in Glucose 3-Hour AUC at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Glucose 3-Hour AUC at Week 54 | -21.1 mg*hr/dL | Standard Deviation 47.7 |
| Placebo/Metformin | Change From Baseline in Glucose 3-Hour AUC at Week 54 | -36.0 mg*hr/dL | Standard Deviation 136.1 |
| Metformin | Change From Baseline in Glucose 3-Hour AUC at Week 54 | -73.1 mg*hr/dL | Standard Deviation 95.8 |
| Placebo/Sitagliptin | Change From Baseline in Glucose 3-Hour AUC at Week 54 | -63.3 mg*hr/dL | — |
Secondary
Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20 | -49.3 mg*hr/dL | Standard Deviation 103.6 |
| Placebo/Metformin | Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20 | 2.0 mg*hr/dL | Standard Deviation 190 |
| Metformin | Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20 | 18.6 mg*hr/dL | Standard Deviation 50.9 |
| Placebo/Sitagliptin | Change From Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20 | 191.0 mg*hr/dL | Standard Deviation 434.2 |
Secondary
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20 | -43.5 mg*hr/dL | Standard Deviation 97.4 |
| Placebo/Metformin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20 | 10.8 mg*hr/dL | Standard Deviation 58.6 |
| Metformin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20 | 39.8 mg*hr/dL | Standard Deviation 50.1 |
| Placebo/Sitagliptin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 20 | 46.2 mg*hr/dL | Standard Deviation 201.9 |
Secondary
Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54 | -30.7 mg*hr/dL | Standard Deviation 100.7 |
| Placebo/Metformin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54 | -50.1 mg*hr/dL | Standard Deviation 79.5 |
| Metformin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54 | -49.0 mg*hr/dL | Standard Deviation 87.5 |
| Placebo/Sitagliptin | Change From Baseline in Glucose Excursion 3-Hour AUC at Week 54 | -74.0 mg*hr/dL | — |
Secondary
Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin | -6.13 Index of insulin resistance | Standard Deviation 34.86 |
| Placebo/Metformin | Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin | -1.30 Index of insulin resistance | Standard Deviation 15.31 |
| Metformin | Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin | -15.18 Index of insulin resistance | Standard Deviation 36.41 |
| Placebo/Sitagliptin | Change From Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin | -2.21 Index of insulin resistance | — |
Secondary
Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin | -41.15 Percentage of Beta Cell Function | Standard Deviation 183.17 |
| Placebo/Metformin | Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin | -63.88 Percentage of Beta Cell Function | Standard Deviation 339.74 |
| Metformin | Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin | -1860.69 Percentage of Beta Cell Function | Standard Deviation 4099.22 |
| Placebo/Sitagliptin | Change From Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin | -121.48 Percentage of Beta Cell Function | — |
Secondary
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin | -0.50 Index of insulin resistance | Standard Deviation 31.62 |
| Placebo/Metformin | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin | -0.86 Index of insulin resistance | Standard Deviation 9.02 |
| Metformin | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin | -4.46 Index of insulin resistance | Standard Deviation 34.65 |
| Placebo/Sitagliptin | Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin | 2.58 Index of insulin resistance | Standard Deviation 9.3 |
Secondary
Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin | 15.72 Percentage of Beta Cell Function | Standard Deviation 162.47 |
| Placebo/Metformin | Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin | -53.23 Percentage of Beta Cell Function | Standard Deviation 296.23 |
| Metformin | Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin | -1757.50 Percentage of Beta Cell Function | Standard Deviation 4765.46 |
| Placebo/Sitagliptin | Change From Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin | -64.78 Percentage of Beta Cell Function | Standard Deviation 126.65 |
Secondary
Change From Baseline in Insulin 3-hour AUC at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin 3-hour AUC at Week 20 | -14.5 µIU*hr/mL | Standard Deviation 128 |
| Placebo/Metformin | Change From Baseline in Insulin 3-hour AUC at Week 20 | -32.8 µIU*hr/mL | Standard Deviation 99.9 |
| Metformin | Change From Baseline in Insulin 3-hour AUC at Week 20 | 141.7 µIU*hr/mL | Standard Deviation 206.1 |
| Placebo/Sitagliptin | Change From Baseline in Insulin 3-hour AUC at Week 20 | -145.6 µIU*hr/mL | Standard Deviation 180.6 |
Secondary
Change From Baseline in Insulin 3-Hour AUC at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin 3-Hour AUC at Week 54 | -43.2 µIU*hr/mL | Standard Deviation 259.8 |
| Placebo/Metformin | Change From Baseline in Insulin 3-Hour AUC at Week 54 | -253.9 µIU*hr/mL | Standard Deviation 282.7 |
| Metformin | Change From Baseline in Insulin 3-Hour AUC at Week 54 | -37.8 µIU*hr/mL | Standard Deviation 9.4 |
| Placebo/Sitagliptin | Change From Baseline in Insulin 3-Hour AUC at Week 54 | -184.4 µIU*hr/mL | — |
Secondary
Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20 | 0.0 [µIU*hr/mL]/[mg*hr/dL] | Standard Deviation 0.3 |
| Placebo/Metformin | Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20 | -0.1 [µIU*hr/mL]/[mg*hr/dL] | Standard Deviation 0.3 |
| Metformin | Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20 | 0.2 [µIU*hr/mL]/[mg*hr/dL] | Standard Deviation 0.4 |
| Placebo/Sitagliptin | Change From Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20 | -0.2 [µIU*hr/mL]/[mg*hr/dL] | Standard Deviation 0.3 |
Secondary
Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54 | -0.1 [μIU*hr/mL]/[mg*hr/dL] | Standard Deviation 0.5 |
| Placebo/Metformin | Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54 | -0.6 [μIU*hr/mL]/[mg*hr/dL] | Standard Deviation 0.8 |
| Metformin | Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54 | -0.0 [μIU*hr/mL]/[mg*hr/dL] | Standard Deviation 0.2 |
| Placebo/Sitagliptin | Change From Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54 | -0.3 [μIU*hr/mL]/[mg*hr/dL] | — |
Secondary
Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin
This change from baseline reflects the Week 20 insulin minus the Week 0 insulin.
Time frame: Baseline and Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin | 1.59 mIU/L | Standard Deviation 47.24 |
| Placebo/Metformin | Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin | -3.91 mIU/L | Standard Deviation 22.31 |
| Metformin | Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin | -7.25 mIU/L | Standard Deviation 60.58 |
| Placebo/Sitagliptin | Change From Baseline in Insulin at Week 20 for Participants Not on Background Insulin | -1.23 mIU/L | Standard Deviation 20.55 |
Secondary
Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin
This change from baseline reflects the Week 54 insulin minus the Week 0 insulin.
Time frame: Baseline and Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin | -9.65 mIU/L | Standard Deviation 40.82 |
| Placebo/Metformin | Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin | -6.64 mIU/L | Standard Deviation 32.01 |
| Metformin | Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin | -20.50 mIU/L | Standard Deviation 65.08 |
| Placebo/Sitagliptin | Change From Baseline in Insulin at Week 54 For Participants Not on Background Insulin | -9.95 mIU/L | — |
Secondary
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20 | -12.4 µIU*hr/mL | Standard Deviation 89.4 |
| Placebo/Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20 | -19.4 µIU*hr/mL | Standard Deviation 93.6 |
| Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20 | 87.5 µIU*hr/mL | Standard Deviation 124.5 |
| Placebo/Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 20 | -82.8 µIU*hr/mL | Standard Deviation 93.4 |
Secondary
Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54 | -103.8 µIU*hr/mL | Standard Deviation 151 |
| Placebo/Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54 | -198.5 µIU*hr/mL | Standard Deviation 263 |
| Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54 | -40.2 µIU*hr/mL | Standard Deviation 11.5 |
| Placebo/Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC at Week 54 | -116.6 µIU*hr/mL | — |
Secondary
Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20 | 2.2 [μIU*hr/mL]/[mg*hr/dL] | Standard Deviation 9.6 |
| Placebo/Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20 | 7.2 [μIU*hr/mL]/[mg*hr/dL] | Standard Deviation 17.5 |
| Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20 | -2.5 [μIU*hr/mL]/[mg*hr/dL] | Standard Deviation 3.2 |
| Placebo/Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20 | 1.4 [μIU*hr/mL]/[mg*hr/dL] | Standard Deviation 2.2 |
Secondary
Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54 | 4.1 [µIU*hr/mL]/[mg*hr/dL] | Standard Deviation 13.1 |
| Placebo/Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54 | 3.7 [µIU*hr/mL]/[mg*hr/dL] | Standard Deviation 5.6 |
| Metformin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54 | -2.7 [µIU*hr/mL]/[mg*hr/dL] | Standard Deviation 4.3 |
| Placebo/Sitagliptin | Change From Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54 | 1.4 [µIU*hr/mL]/[mg*hr/dL] | — |
Secondary
Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin
This change from baseline reflects the Week 20 proinsulin minus the Week 0 proinsulin.
Time frame: Baseline and Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin | 0.91 pmol/L | Standard Deviation 81.88 |
| Placebo/Metformin | Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin | -10.88 pmol/L | Standard Deviation 55.12 |
| Metformin | Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin | 12.57 pmol/L | Standard Deviation 36.98 |
| Placebo/Sitagliptin | Change From Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin | -1.33 pmol/L | Standard Deviation 9.07 |
Secondary
Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin
This change from baseline reflects the Week 54 proinsulin minus the Week 0 proinsulin.
Time frame: Baseline and Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin | -10.62 pmol/L | Standard Deviation 67.54 |
| Placebo/Metformin | Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin | -16.13 pmol/L | Standard Deviation 81.52 |
| Metformin | Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin | -23.30 pmol/L | Standard Deviation 42.36 |
| Placebo/Sitagliptin | Change From Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin | -0.50 pmol/L | — |
Secondary
Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin
Change from baseline was the Week 20 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.
Time frame: Baseline and Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin | 0.02 Ratio | Standard Deviation 0.22 |
| Placebo/Metformin | Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin | 0.02 Ratio | Standard Deviation 0.16 |
| Metformin | Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin | -0.03 Ratio | Standard Deviation 0.1 |
| Placebo/Sitagliptin | Change From Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin | -0.19 Ratio | Standard Deviation 0.45 |
Secondary
Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin
The change from baseline was Week 54 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio.
Time frame: Baseline and Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin | 0.02 Ratio | Standard Deviation 0.23 |
| Placebo/Metformin | Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin | -0.03 Ratio | Standard Deviation 0.19 |
| Metformin | Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin | -0.01 Ratio | Standard Deviation 0.06 |
| Placebo/Sitagliptin | Change From Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin | 0.02 Ratio | — |
Secondary
Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females | 0.1 Score on a scale | Standard Deviation 0.4 |
| Placebo/Metformin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females | 0.1 Score on a scale | Standard Deviation 0.3 |
| Metformin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females | 0.2 Score on a scale | Standard Deviation 0.4 |
| Placebo/Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Females | 0.0 Score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males | 0.3 Score on a scale | Standard Deviation 0.5 |
| Placebo/Metformin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males | 0.2 Score on a scale | Standard Deviation 0.4 |
| Metformin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males | 0.0 Score on a scale | — |
| Placebo/Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 20 - Males | 0.5 Score on a scale | Standard Deviation 0.7 |
Secondary
Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females | 0.5 Score on a scale | Standard Deviation 0.6 |
| Placebo/Metformin | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females | 0.3 Score on a scale | Standard Deviation 0.5 |
| Metformin | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females | 0.8 Score on a scale | Standard Deviation 1.5 |
| Placebo/Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Females | 0.3 Score on a scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males | 0.5 Score on a scale | Standard Deviation 0.7 |
| Placebo/Metformin | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males | 0.6 Score on a scale | Standard Deviation 0.5 |
| Placebo/Sitagliptin | Change From Baseline in Tanner Stage for Pubic Hair at Week 54 - Males | 0.5 Score on a scale | Standard Deviation 0.7 |
Secondary
Change From Baseline in Tanner Staging for Breasts at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Staging for Breasts at Week 20 - Females | 0.2 Score on a Scale | Standard Deviation 0.6 |
| Placebo/Metformin | Change From Baseline in Tanner Staging for Breasts at Week 20 - Females | 0.1 Score on a Scale | Standard Deviation 0.3 |
| Metformin | Change From Baseline in Tanner Staging for Breasts at Week 20 - Females | 0.2 Score on a Scale | Standard Deviation 0.4 |
| Placebo/Sitagliptin | Change From Baseline in Tanner Staging for Breasts at Week 20 - Females | 0.3 Score on a Scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in Tanner Staging for Breasts at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Staging for Breasts at Week 54 - Females | 0.5 Score on a Scale | Standard Deviation 0.7 |
| Placebo/Metformin | Change From Baseline in Tanner Staging for Breasts at Week 54 - Females | 0.4 Score on a Scale | Standard Deviation 0.6 |
| Metformin | Change From Baseline in Tanner Staging for Breasts at Week 54 - Females | 0.5 Score on a Scale | Standard Deviation 1 |
| Placebo/Sitagliptin | Change From Baseline in Tanner Staging for Breasts at Week 54 - Females | 0.7 Score on a Scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males | 0.3 Score on a scale | Standard Deviation 0.5 |
| Placebo/Metformin | Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males | 0.2 Score on a scale | Standard Deviation 0.4 |
| Metformin | Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males | 0.0 Score on a scale | — |
| Placebo/Sitagliptin | Change From Baseline in Tanner Staging for Genitalia at Week 20 - Males | 0.5 Score on a scale | Standard Deviation 0.7 |
Secondary
Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males | 0.5 Score on a scale | Standard Deviation 0.6 |
| Placebo/Metformin | Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males | 0.6 Score on a scale | Standard Deviation 0.7 |
| Placebo/Sitagliptin | Change From Baseline in Tanner Staging for Genitalia at Week 54 - Males | 0.6 Score on a scale | Standard Deviation 0.7 |
Secondary
Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females | -88.4 nmol(BCE)/mmol(creatinine) | Standard Deviation 102.6 |
| Placebo/Metformin | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females | -61.2 nmol(BCE)/mmol(creatinine) | Standard Deviation 137.6 |
| Metformin | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females | -80.3 nmol(BCE)/mmol(creatinine) | Standard Deviation 208.5 |
| Placebo/Sitagliptin | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Females | -17.0 nmol(BCE)/mmol(creatinine) | Standard Deviation 13.5 |
Secondary
Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males | -78.2 nmol(BCE)/mmol(creatinine) | Standard Deviation 166.9 |
| Placebo/Metformin | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males | -102.4 nmol(BCE)/mmol(creatinine) | Standard Deviation 267.7 |
| Placebo/Sitagliptin | Change From Baseline in u-NTx/Creatinine Ratio at Week 54 - Males | -30.0 nmol(BCE)/mmol(creatinine) | — |
Secondary
Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females | -28.7 nmol(BCE)/mmol(creatinine) | Standard Deviation 120.9 |
| Placebo/Metformin | Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females | -41.2 nmol(BCE)/mmol(creatinine) | Standard Deviation 148.9 |
| Metformin | Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females | -98.0 nmol(BCE)/mmol(creatinine) | Standard Deviation 153 |
| Placebo/Sitagliptin | Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females | 12.7 nmol(BCE)/mmol(creatinine) | Standard Deviation 29.2 |
Secondary
Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males | -30.9 nmol(BCE)/mmol(creatinine) | Standard Deviation 167.2 |
| Placebo/Metformin | Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males | -69.8 nmol(BCE)/mmol(creatinine) | Standard Deviation 162.1 |
| Metformin | Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males | 62.0 nmol(BCE)/mmol(creatinine) | — |
| Placebo/Sitagliptin | Change From Baseline u-NTx/Creatinine Ratio at Week 20 - Males | -29.0 nmol(BCE)/mmol(creatinine) | Standard Deviation 32.5 |
Secondary
Growth Velocity at Week 20 - Females
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Time frame: Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Growth Velocity at Week 20 - Females | 3.2 cm/year | Standard Deviation 8.2 |
| Placebo/Metformin | Growth Velocity at Week 20 - Females | 1.9 cm/year | Standard Deviation 2.7 |
| Metformin | Growth Velocity at Week 20 - Females | 5.0 cm/year | Standard Deviation 6.8 |
| Placebo/Sitagliptin | Growth Velocity at Week 20 - Females | 0.6 cm/year | Standard Deviation 1.6 |
Secondary
Growth Velocity at Week 20 - Males
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Time frame: Week 20
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Growth Velocity at Week 20 - Males | 2.6 cm/year | Standard Deviation 2.7 |
| Placebo/Metformin | Growth Velocity at Week 20 - Males | 3.6 cm/year | Standard Deviation 3.2 |
| Metformin | Growth Velocity at Week 20 - Males | -1.0 cm/year | Standard Deviation 1.3 |
| Placebo/Sitagliptin | Growth Velocity at Week 20 - Males | 1.7 cm/year | Standard Deviation 2.4 |
Secondary
Growth Velocity at Week 54 - Females
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Time frame: Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Growth Velocity at Week 54 - Females | 2.1 cm/year | Standard Deviation 3.7 |
| Placebo/Metformin | Growth Velocity at Week 54 - Females | 1.2 cm/year | Standard Deviation 1.8 |
| Metformin | Growth Velocity at Week 54 - Females | 2.4 cm/year | Standard Deviation 2.9 |
| Placebo/Sitagliptin | Growth Velocity at Week 54 - Females | 0.7 cm/year | Standard Deviation 1 |
Secondary
Growth Velocity at Week 54 - Males
Growth Velocity (cm/year) = (Change from Baseline in height)/(Change from Baseline in chronologic age).
Time frame: Week 54
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Growth Velocity at Week 54 - Males | 2.5 cm/year | Standard Deviation 2.5 |
| Placebo/Metformin | Growth Velocity at Week 54 - Males | 2.8 cm/year | Standard Deviation 2.1 |
| Metformin | Growth Velocity at Week 54 - Males | 1.7 cm/year | — |
| Placebo/Sitagliptin | Growth Velocity at Week 54 - Males | 2.8 cm/year | Standard Deviation 4 |
Secondary
Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20 | 4.06 Percent Change | Standard Deviation 19.25 |
| Placebo/Metformin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20 | -1.78 Percent Change | Standard Deviation 17.18 |
| Metformin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20 | 4.89 Percent Change | Standard Deviation 1.9 |
| Placebo/Sitagliptin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 20 | 14.57 Percent Change | Standard Deviation 15.46 |
Secondary
Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54 | 4.74 Percent Change | Standard Deviation 17.18 |
| Placebo/Metformin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54 | 4.27 Percent Change | Standard Deviation 18.24 |
| Metformin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54 | 12.63 Percent Change | Standard Deviation 13.02 |
| Placebo/Sitagliptin | Mean Percent Change of Peripheral Blood Mononuclear Cells Expressing CD26 From Baseline at Week 54 | -5.30 Percent Change | Standard Deviation 4.19 |
Secondary
Participants With Worsening in Dental Status at 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.
Time frame: Week 20
Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had dental data at baseline and Week 20.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 1. With ≥1 tooth with worsening in any category | 32 Participants |
| Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 2. With ≥1 tooth with worsening fracture | 5 Participants |
| Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 3. With ≥1 tooth with worsening discoloration | 29 Participants |
| Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 4. With ≥1 tooth with worsening enamel defect | 7 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 20 | 2. With ≥1 tooth with worsening fracture | 5 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 20 | 3. With ≥1 tooth with worsening discoloration | 23 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 20 | 4. With ≥1 tooth with worsening enamel defect | 4 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 20 | 1. With ≥1 tooth with worsening in any category | 25 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 20 | 3. With ≥1 tooth with worsening discoloration | 0 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 20 | 2. With ≥1 tooth with worsening fracture | 0 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 20 | 4. With ≥1 tooth with worsening enamel defect | 1 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 20 | 1. With ≥1 tooth with worsening in any category | 1 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 4. With ≥1 tooth with worsening enamel defect | 0 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 2. With ≥1 tooth with worsening fracture | 0 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 1. With ≥1 tooth with worsening in any category | 0 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 20 | 3. With ≥1 tooth with worsening discoloration | 0 Participants |
Secondary
Participants With Worsening in Dental Status at 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.
Time frame: Week 54
Population: The analysis population included all randomized participants who received ≥1 dose of study medication and had dental data at baseline and Week 54.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 4. With ≥1 with worsening enamel defect | 13 Participants |
| Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 3. With ≥1 tooth with worsening discoloration | 45 Participants |
| Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 1. With ≥1 tooth with worsening in any category | 49 Participants |
| Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 2. With ≥1 tooth with worsening fracture | 13 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 54 | 2. With ≥1 tooth with worsening fracture | 15 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 54 | 1. With ≥1 tooth with worsening in any category | 50 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 54 | 3. With ≥1 tooth with worsening discoloration | 48 Participants |
| Placebo/Metformin | Participants With Worsening in Dental Status at Week 54 | 4. With ≥1 with worsening enamel defect | 13 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 54 | 3. With ≥1 tooth with worsening discoloration | 2 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 54 | 4. With ≥1 with worsening enamel defect | 1 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 54 | 2. With ≥1 tooth with worsening fracture | 1 Participants |
| Metformin | Participants With Worsening in Dental Status at Week 54 | 1. With ≥1 tooth with worsening in any category | 2 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 4. With ≥1 with worsening enamel defect | 0 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 1. With ≥1 tooth with worsening in any category | 0 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 2. With ≥1 tooth with worsening fracture | 0 Participants |
| Placebo/Sitagliptin | Participants With Worsening in Dental Status at Week 54 | 3. With ≥1 tooth with worsening discoloration | 0 Participants |
Secondary
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
The percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.
Time frame: Up to Week 20
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 5.3 Percentage of participants |
| Placebo/Metformin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 11.1 Percentage of participants |
| Metformin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 0.0 Percentage of participants |
| Placebo/Sitagliptin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 40.0 Percentage of participants |
Secondary
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54
The percentage of participants who initiated glycemic rescue therapy prior to Week 54 was reported.
Time frame: Up to Week 54
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54 | 35.8 Percentage of participants |
| Placebo/Metformin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54 | 28.9 Percentage of participants |
| Metformin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54 | 11.1 Percentage of participants |
| Placebo/Sitagliptin | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54 | 80.0 Percentage of participants |
Secondary
Percentage of Participants With A1C at Goal (<6.5%) at 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).
Time frame: Week 20
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | 30.5 Percentage of participants |
| Placebo/Metformin | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | 23.3 Percentage of participants |
| Metformin | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | 66.7 Percentage of participants |
| Placebo/Sitagliptin | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | 20.0 Percentage of participants |
Secondary
Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
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
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | 30.5 Percentage of Participants |
| Placebo/Metformin | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | 23.2 Percentage of Participants |
p-value: =0.63995% CI: [-11.6, 18.3]Miettinen and Nurminen
Secondary
Percentage of Participants With A1C at Goal (<6.5%) at 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).
Time frame: Week 54
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | 20.0 Percentage of participants |
| Placebo/Metformin | Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | 35.6 Percentage of participants |
| Metformin | Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | 22.2 Percentage of participants |
| Placebo/Sitagliptin | Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | 20.0 Percentage of participants |
Secondary
Percentage of Participants With A1C at Goal (<7.0%) at 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).
Time frame: Week 20
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | 49.5 Percentage of Participants |
| Placebo/Metformin | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | 37.8 Percentage of Participants |
| Metformin | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | 77.8 Percentage of Participants |
| Placebo/Sitagliptin | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | 20.0 Percentage of Participants |
Secondary
Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled))
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
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | 49.5 Percentage of participants |
| Placebo/Metformin | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (Pooled)) | 36.8 Percentage of participants |
p-value: =0.37495% CI: [-8.1, 21.2]Miettinen and Nurminen
Secondary
Percentage of Participants With A1C at Goal (<7.0%) at 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).
Time frame: Week 54
Population: The analysis population included all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | 28.4 Percentage of participants |
| Placebo/Metformin | Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | 40.0 Percentage of participants |
| Metformin | Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | 33.3 Percentage of participants |
| Placebo/Sitagliptin | Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | 20.0 Percentage of participants |
Secondary
Percent Change From Baseline in IGF-1 at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in IGF-1 at Week 20 - Males | -2.7 Percent Change | Standard Deviation 22.1 |
| Placebo/Metformin | Percent Change From Baseline in IGF-1 at Week 20 - Males | 9.3 Percent Change | Standard Deviation 29.6 |
| Metformin | Percent Change From Baseline in IGF-1 at Week 20 - Males | 7.6 Percent Change | Standard Deviation 17.4 |
| Placebo/Sitagliptin | Percent Change From Baseline in IGF-1 at Week 20 - Males | 5.3 Percent Change | Standard Deviation 16.2 |
Secondary
Percent Change From Baseline in IGF-1 at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in IGF-1 at Week 54 - Females | -1.5 Percent Change | Standard Deviation 34.4 |
| Placebo/Metformin | Percent Change From Baseline in IGF-1 at Week 54 - Females | 7.2 Percent Change | Standard Deviation 57.6 |
| Metformin | Percent Change From Baseline in IGF-1 at Week 54 - Females | -11.9 Percent Change | Standard Deviation 13.4 |
| Placebo/Sitagliptin | Percent Change From Baseline in IGF-1 at Week 54 - Females | -13.5 Percent Change | — |
Secondary
Percent Change From Baseline in IGF-1 at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in IGF-1 at Week 54 - Males | -4.9 Percent Change | Standard Deviation 33.5 |
| Placebo/Metformin | Percent Change From Baseline in IGF-1 at Week 54 - Males | 29.6 Percent Change | Standard Deviation 99.8 |
| Metformin | Percent Change From Baseline in IGF-1 at Week 54 - Males | 18.8 Percent Change | — |
| Placebo/Sitagliptin | Percent Change From Baseline in IGF-1 at Week 54 - Males | -6.8 Percent Change | Standard Deviation 22.1 |
Secondary
Percent Change From Baseline in IGF-BP3 at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in IGF-BP3 at Week 20 - Males | 5.6 Percent Change | Standard Deviation 13.3 |
| Placebo/Metformin | Percent Change From Baseline in IGF-BP3 at Week 20 - Males | 10.2 Percent Change | Standard Deviation 18.6 |
| Metformin | Percent Change From Baseline in IGF-BP3 at Week 20 - Males | 3.3 Percent Change | Standard Deviation 0.5 |
| Placebo/Sitagliptin | Percent Change From Baseline in IGF-BP3 at Week 20 - Males | 14.2 Percent Change | Standard Deviation 50.6 |
Secondary
Percent Change From Baseline in IGF-BP3 at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in IGF-BP3 at Week 54 - Females | 2.0 Percent Change | Standard Deviation 16.7 |
| Placebo/Metformin | Percent Change From Baseline in IGF-BP3 at Week 54 - Females | 4.5 Percent Change | Standard Deviation 17 |
| Metformin | Percent Change From Baseline in IGF-BP3 at Week 54 - Females | 11.4 Percent Change | Standard Deviation 17.4 |
| Placebo/Sitagliptin | Percent Change From Baseline in IGF-BP3 at Week 54 - Females | -13.4 Percent Change | Standard Deviation 9.9 |
Secondary
Percent Change From Baseline in IGF-BP3 at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in IGF-BP3 at Week 54 - Males | 5.4 Percent Change | Standard Deviation 18.4 |
| Placebo/Metformin | Percent Change From Baseline in IGF-BP3 at Week 54 - Males | 18.2 Percent Change | Standard Deviation 43.1 |
| Metformin | Percent Change From Baseline in IGF-BP3 at Week 54 - Males | -2.9 Percent Change | — |
| Placebo/Sitagliptin | Percent Change From Baseline in IGF-BP3 at Week 54 - Males | 22.5 Percent Change | Standard Deviation 8.3 |
Secondary
Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females | 0.5 Percent Change | Standard Deviation 21.9 |
| Placebo/Metformin | Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females | 11.0 Percent Change | Standard Deviation 34 |
| Metformin | Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females | -3.2 Percent Change | Standard Deviation 14.9 |
| Placebo/Sitagliptin | Percent Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females | 41.4 Percent Change | Standard Deviation 31.2 |
Secondary
Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females | 3.5 Percent Change | Standard Deviation 18.2 |
| Placebo/Metformin | Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females | 3.8 Percent Change | Standard Deviation 13.8 |
| Metformin | Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females | 8.4 Percent Change | Standard Deviation 12.9 |
| Placebo/Sitagliptin | Percent Change From Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females | -0.7 Percent Change | Standard Deviation 24.1 |
Secondary
Skeletal Maturation at Week 20 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Skeletal Maturation at Week 20 - Females | 0.6 Ratio | Standard Deviation 1.9 |
| Placebo/Metformin | Skeletal Maturation at Week 20 - Females | 0.4 Ratio | Standard Deviation 1.8 |
| Metformin | Skeletal Maturation at Week 20 - Females | 1.7 Ratio | Standard Deviation 2.3 |
| Placebo/Sitagliptin | Skeletal Maturation at Week 20 - Females | -0.8 Ratio | Standard Deviation 5.5 |
Secondary
Skeletal Maturation at Week 20 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Skeletal Maturation at Week 20 - Males | 1.6 Ratio | Standard Deviation 1.7 |
| Placebo/Metformin | Skeletal Maturation at Week 20 - Males | 1.2 Ratio | Standard Deviation 1.1 |
| Metformin | Skeletal Maturation at Week 20 - Males | 0.4 Ratio | — |
| Placebo/Sitagliptin | Skeletal Maturation at Week 20 - Males | 2.4 Ratio | — |
Secondary
Skeletal Maturation at Week 54 - Females
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Skeletal Maturation at Week 54 - Females | 1.3 Ratio | Standard Deviation 1.1 |
| Placebo/Metformin | Skeletal Maturation at Week 54 - Females | 1.0 Ratio | Standard Deviation 0.6 |
| Metformin | Skeletal Maturation at Week 54 - Females | 1.3 Ratio | Standard Deviation 2.2 |
Secondary
Skeletal Maturation at Week 54 - Males
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Skeletal Maturation at Week 54 - Males | 1.3 Ratio | Standard Deviation 0.9 |
| Placebo/Metformin | Skeletal Maturation at Week 54 - Males | 1.3 Ratio | Standard Deviation 0.6 |