Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to determine the safety and effectiveness of an investigational drug in patients with Type 2 Diabetes Mellitus (T2DM) (a specific type of diabetes).
Interventions
DRUGComparator: MK0431 50 mg b.i.d. (b.i.d. = twice daily)
MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take MK0431 50 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.
DRUGComparator: MK0431 100 mg q.d. (q.d. = once daily)
MK0431 oral tablets will be started on Day 1 as two 50 mg tablets (100 mg q.d.) (q.d. = once daily) and continued at this dose throughout the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.
DRUGComparator: Placebo (Phase A)/Metformin (Phase B)
During the placebo-controlled period (Day 1 through Week 24/Phase A), metformin and MK0431 matching placebos will be dispensed as oral tablets. At the beginning of the 30-week active-controlled period (Phase B), metformin will be started as 500 mg q.d. (q.d. = once daily) and up-titrated in 500 mg weekly increments to a stable dose of 1000 mg b.i.d. Patients who complete the 54-week base study and who enter the 50-week extension study will continue to take metformin 1000 mg b.i.d. (b.i.d. = twice daily) for a total placebo/metformin treatment duration of up to 104 weeks.
DRUGComparator: Metformin 500 mg b.i.d.
Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased after 1 week to a stable dose of 500 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 500 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.
DRUGComparator: Open-Label MK0431/Metformin 50/1000 mg b.i.d.
MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Metformin oral tablets will be started on Day 1 at 500 mg q.d. and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. The open-label treatment period is 24 weeks.
DRUGComparator: Metformin 1000 mg b.i.d.
Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 1000 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
54-Week Base Study: * Patients between the ages of 18 and 78 with Type 2 Diabetes Mellitus (a specific type of diabetes) 50-Week Extension Study: * Patients who complete the 54-week base study are eligible to enter the 50-week extension study
Exclusion criteria
* Patients who do not have Type 2 Diabetes Mellitus (a specific type of diabetes)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | Week 24 | HbA1c is measured as a percent. This change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. |
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | Week 54 | HbA1c is measured as a percent. This change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent. |
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0. |
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. |
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | Week 104 | HbA1c is measured as a percent. This change from baseline reflects the Week 104 HbA1c percent minus the Week 0 HbA1c percent. |
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | Week 104 | Change from baseline at Week 104 is defined as Week 104 minus Week 0. |
| Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | Week 104 | Change from baseline at Week 104 is defined as Week 104 minus Week 0. |
| Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0. |
Participant flow
Recruitment details
First Patient In: 01-Apr-2005 Last Patient Last Visit: 29-Feb-2008 140 study centers worldwide
Pre-assignment details
Patients 18-78 years with T2DM and an HbA1c 7.5-11% on diet/exercise were eligible for randomization into the 54-week (wk) base study. Patients with an HbA1c \>11% or glucose \>280 mg/dL were eligible to participate in the Open-label Cohort through Wk 24. Randomized patients who completed the base study were eligible to enter a 50-wk extension study.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg q.d. The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study. | 179 |
| Metformin 500 mg b.i.d. The Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). | 182 |
| Metformin 1000 mg b.i.d. The Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). | 182 |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). | 190 |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). | 182 |
| Placebo/Metformin 1000 mg b.i.d. The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks. | 176 |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) OLC (Open-label Cohort) includes data from non-randomized patients assigned to receive treatment with open-label, oral tablets of sitagliptin and metformin. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning on Day 1. The dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients continued to take open-label sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the Phase A treatment period of up to 24 weeks. Results presented for the OLC are through Week 24. Patients in the OLC completed the study at Week 24. | 117 |
| Total | 1,208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| 50-Week Extension Study | Adverse Event | 2 | 3 | 2 | 0 | 1 | 1 | 0 |
| 50-Week Extension Study | Death | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| 50-Week Extension Study | Lack of Efficacy | 26 | 15 | 13 | 16 | 8 | 8 | 0 |
| 50-Week Extension Study | Lost to Follow-up | 4 | 0 | 1 | 4 | 3 | 3 | 0 |
| 50-Week Extension Study | non-compliance with study procedures | 1 | 0 | 0 | 1 | 1 | 0 | 0 |
| 50-Week Extension Study | patient moved | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
| 50-Week Extension Study | patient scheduled for elective surgery | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| 50-Week Extension Study | Physician Decision | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| 50-Week Extension Study | Pregnancy | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| 50-Week Extension Study | protocol discontinuation criteria | 2 | 2 | 3 | 2 | 3 | 3 | 0 |
| 50-Week Extension Study | Protocol Violation | 1 | 1 | 1 | 2 | 0 | 1 | 0 |
| 50-Week Extension Study | reason unspecified | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| 50-Week Extension Study | Withdrawal by Subject | 2 | 5 | 2 | 8 | 3 | 3 | 0 |
| 54-Week Base Study | Adverse Event | 12 | 9 | 11 | 6 | 5 | 11 | 3 |
| 54-Week Base Study | Death | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| 54-Week Base Study | laboratory reporting error | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| 54-Week Base Study | Lack of Efficacy | 11 | 14 | 8 | 4 | 3 | 14 | 19 |
| 54-Week Base Study | Lost to Follow-up | 5 | 4 | 7 | 5 | 10 | 9 | 3 |
| 54-Week Base Study | non-compliance with study procedures | 1 | 2 | 0 | 0 | 0 | 2 | 0 |
| 54-Week Base Study | patient incarcerated | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| 54-Week Base Study | patient intolerance to rescue therapy | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| 54-Week Base Study | patient moved | 0 | 1 | 1 | 2 | 3 | 1 | 0 |
| 54-Week Base Study | Physician Decision | 1 | 1 | 0 | 0 | 1 | 0 | 0 |
| 54-Week Base Study | Pregnancy | 1 | 0 | 0 | 0 | 1 | 0 | 1 |
| 54-Week Base Study | protocol discontinuation criteria | 2 | 5 | 2 | 6 | 5 | 3 | 5 |
| 54-Week Base Study | Protocol Violation | 6 | 4 | 2 | 4 | 0 | 3 | 3 |
| 54-Week Base Study | site error | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| 54-Week Base Study | Withdrawal by Subject | 17 | 16 | 16 | 15 | 10 | 15 | 4 |
Baseline characteristics
| Characteristic | Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC | Total | Sitagliptin 100 mg q.d. | Metformin 500 mg b.i.d. | Metformin 1000 mg b.i.d. | Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Placebo/Metformin 1000 mg b.i.d. |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 10 | 53.4 years STANDARD_DEVIATION 9.9 | 53.3 years STANDARD_DEVIATION 10.2 | 53.4 years STANDARD_DEVIATION 10.2 | 53.2 years STANDARD_DEVIATION 9.6 | 54.1 years STANDARD_DEVIATION 10 | 53.3 years STANDARD_DEVIATION 9.6 | 53.6 years STANDARD_DEVIATION 10 |
| HbA1c (Hemoglobin A1c) | 11.2 Percent STANDARD_DEVIATION 1.2 | 9.0 Percent STANDARD_DEVIATION 1.2 | 8.9 Percent STANDARD_DEVIATION 1 | 8.9 Percent STANDARD_DEVIATION 1 | 8.7 Percent STANDARD_DEVIATION 0.9 | 8.8 Percent STANDARD_DEVIATION 1 | 8.7 Percent STANDARD_DEVIATION 0.9 | 8.7 Percent STANDARD_DEVIATION 1 |
| Race/Ethnicity, Customized Asian | 1 participants | 63 participants | 6 participants | 14 participants | 10 participants | 9 participants | 11 participants | 12 participants |
| Race/Ethnicity, Customized Black | 9 participants | 85 participants | 11 participants | 12 participants | 9 participants | 13 participants | 14 participants | 17 participants |
| Race/Ethnicity, Customized Hispanic | 54 participants | 351 participants | 52 participants | 55 participants | 39 participants | 55 participants | 49 participants | 47 participants |
| Race/Ethnicity, Customized Other | 9 participants | 101 participants | 17 participants | 14 participants | 18 participants | 11 participants | 13 participants | 19 participants |
| Race/Ethnicity, Customized White | 44 participants | 608 participants | 93 participants | 87 participants | 106 participants | 102 participants | 95 participants | 81 participants |
| Sex: Female, Male Female | 50 Participants | 602 Participants | 86 Participants | 93 Participants | 100 Participants | 85 Participants | 105 Participants | 83 Participants |
| Sex: Female, Male Male | 67 Participants | 606 Participants | 93 Participants | 89 Participants | 82 Participants | 105 Participants | 77 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 71 / — | 74 / — | 99 / — | 87 / — | 94 / — | 73 / — | 40 / — |
| serious Total, serious adverse events | 15 / — | 10 / — | 14 / — | 17 / — | 13 / — | 23 / — | 3 / — |
Outcome results
Primary
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24
HbA1c is measured as a percent. This change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Week 24
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last observed measurement was carried forward to Week 24. The Open-label Cohort group was excluded from the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -0.66 Percent |
| Metformin 500 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -0.82 Percent |
| Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -1.13 Percent |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -1.40 Percent |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -1.90 Percent |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | 0.17 Percent |
Secondary
Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104
Change from baseline at Week 104 is defined as Week 104 minus Week 0.
Time frame: Week 104
Population: The Extension Full Analysis Set (EFAS) included all patients with a baseline value and ≥1 value in the extension (post-Week 54) for this outcome. Data following glycemic rescue were treated as missing. For EFAS patients with no data at Week 104, the last observed measurement was carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | -74.1 mg/dL |
| Metformin 500 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | -72.7 mg/dL |
| Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | -86.7 mg/dL |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | -96.2 mg/dL |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | -110.0 mg/dL |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | -93.3 mg/dL |
Secondary
Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Time frame: Week 24
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last observed measurement was carried forward to Week 24. The Open-label Cohort group was excluded from the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | -51.9 mg/dL |
| Metformin 500 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | -53.4 mg/dL |
| Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | -78.0 mg/dL |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | -92.5 mg/dL |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | -116.6 mg/dL |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | 0.3 mg/dL |
Secondary
Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Time frame: Week 54
Population: The Phase B Full Analysis Set (BFAS) included all patients with a baseline value and ≥1 value in Phase B (post-Week 24) for this outcome. Data following glycemic rescue were treated as missing. For BFAS patients with no data at Week 54, the last observed measurement was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | -45.9 mg/dL |
| Metformin 500 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | -58.6 mg/dL |
| Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | -76.3 mg/dL |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | -89.6 mg/dL |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | -107.9 mg/dL |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | -80.9 mg/dL |
Secondary
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104
Change from baseline at Week 104 is defined as Week 104 minus Week 0.
Time frame: Week 104
Population: The Extension Full Analysis Set (EFAS) included all patients with a baseline value and ≥1 value in the extension (post-Week 54) for this outcome. Data following glycemic rescue were treated as missing. For EFAS patients with no data at Week 104, the last observed measurement was carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | -26.8 mg/dL |
| Metformin 500 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | -41.4 mg/dL |
| Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | -43.2 mg/dL |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | -47.5 mg/dL |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | -57.3 mg/dL |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | -45.2 mg/dL |
Secondary
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Time frame: Week 24
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last observed measurement was carried forward to Week 24. The Open-label Cohort group was excluded from the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -17.5 mg/dL |
| Metformin 500 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -27.3 mg/dL |
| Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -29.3 mg/dL |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -47.1 mg/dL |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -63.9 mg/dL |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | 5.8 mg/dL |
Secondary
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Time frame: Week 54
Population: The Phase B Full Analysis Set (BFAS) included all patients with a baseline value and ≥1 value in Phase B (post-Week 24) for this outcome. Data following glycemic rescue were treated as missing. For BFAS patients with no data at Week 54, the last observed measurement was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -16.0 mg/dL |
| Metformin 500 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -29.0 mg/dL |
| Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -39.6 mg/dL |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -42.5 mg/dL |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -55.6 mg/dL |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | -43.9 mg/dL |
Secondary
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104
HbA1c is measured as a percent. This change from baseline reflects the Week 104 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Week 104
Population: The Extension Full Analysis Set (EFAS) included all patients with a baseline value and ≥1 value in the extension (post-Week 54) for this outcome. Data following glycemic rescue were treated as missing. For EFAS patients with no data at Week 104, the last observed measurement was carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | -1.15 Percent |
| Metformin 500 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | -1.06 Percent |
| Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | -1.34 Percent |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | -1.39 Percent |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | -1.66 Percent |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | -1.39 Percent |
Secondary
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54
HbA1c is measured as a percent. This change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Week 54
Population: The Phase B Full Analysis Set (BFAS) included all patients with a baseline value and ≥1 value in Phase B (post-Week 24) for this outcome. Data following glycemic rescue were treated as missing. For BFAS patients with no data at Week 54, the last observed measurement was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -0.82 Percent |
| Metformin 500 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -1.01 Percent |
| Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -1.34 Percent |
| Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -1.41 Percent |
| Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -1.80 Percent |
| Placebo/Metformin 1000 mg b.i.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | -1.10 Percent |