Diabetes Mellitus, Type II
Conditions
Keywords
Type 2 Diabetes Mellitus
Brief summary
The purpose of this study is to determine the safety and efficacy of an investigational drug in patients with type 2 diabetes mellitus.
Interventions
DRUGPlacebo/Glipizide 5 mg
Placebo (to match Sitagliptin 100 mg) from Visit 4 through Visit 8; Glipizide 5 mg from Visit 8, week 24 to Final Visit (Week 104)
DRUGMetformin
Metformin 1500 mg, once daily, from Visit 2 to Final Visit (Week 104)
Sitagliptin 100 mg once daily, from Visit 4 through Final Visit, week 104
DRUGPioglitazone
Pioglitazone 15 mg once daily, for patients not meeting specific glycemic goals during the placebo-controlled treatment period \[Phase A\], from Visit 5 (Week 6) to Visit 8 (Week 24)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1C (A1C) at Week 24 | Baseline and Week 24 | A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as FPG at Week 24 minus FPG at Week 0. |
| Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as PMG at Week 24 minus PMG at Week 0. |
Participant flow
Recruitment details
Primary therapy Period: 13-Jul-2004 through 02-Feb-2007 (for the 2-year Phase A and B periods); 100 study centers worldwide. (46 sites in the United States, 25 sites in 11 countries in Europe, and 29 sites in 13 countries in the rest of the world).
Pre-assignment details
Patients 18-78 years of age with type 2 diabetes mellitus with inadequate glycemic control (hemoglobin A1C \[A1C\] ≥7% and ≤10%) on stable doses of metformin (≥1500 mg/day) were eligible to enter the 104-week study.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo. | 464 |
| Placebo / Glipizide 5 mg The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral
tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase
B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with
oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated,
in a blinded fashion, to a maximum dose of 15 mg/day. | 237 |
| Total | 701 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase A to Phase B Transition Period | Adverse Event | 2 | 1 |
| Phase A to Phase B Transition Period | Lack of Efficacy | 2 | 2 |
| Phase A to Phase B Transition Period | Patient needed prohibited treatment | 1 | 0 |
| Phase A to Phase B Transition Period | Patient received Phase A rescue therapy | 16 | 23 |
| Phase A to Phase B Transition Period | Poor compliance | 1 | 0 |
| Phase A to Phase B Transition Period | Protocol-Spec lab discon criteria | 1 | 1 |
| Phase A to Phase B Transition Period | Protocol Violation | 0 | 1 |
| Phase A to Phase B Transition Period | Withdrawal by Subject | 1 | 0 |
| Phase A (Weeks 0-24) | Adverse Event | 17 | 9 |
| Phase A (Weeks 0-24) | Lack of Efficacy | 7 | 13 |
| Phase A (Weeks 0-24) | Lost to Follow-up | 4 | 5 |
| Phase A (Weeks 0-24) | Patient Moved | 2 | 3 |
| Phase A (Weeks 0-24) | Patient needed prohibited treatment | 0 | 1 |
| Phase A (Weeks 0-24) | Personal Circumstance | 1 | 0 |
| Phase A (Weeks 0-24) | Poor compliance | 1 | 0 |
| Phase A (Weeks 0-24) | Protocol-Spec lab discon criteria | 4 | 3 |
| Phase A (Weeks 0-24) | Protocol Violation | 3 | 1 |
| Phase A (Weeks 0-24) | Withdrawal by Subject | 10 | 10 |
| Phase B (Weeks 24-104) | Adverse Event | 16 | 10 |
| Phase B (Weeks 24-104) | Discontinued in error | 1 | 0 |
| Phase B (Weeks 24-104) | Lack of Efficacy | 94 | 19 |
| Phase B (Weeks 24-104) | Lost to Follow-up | 13 | 4 |
| Phase B (Weeks 24-104) | Patient Died | 3 | 1 |
| Phase B (Weeks 24-104) | Patient Moved | 2 | 2 |
| Phase B (Weeks 24-104) | Patient needed prohibited treatment | 0 | 1 |
| Phase B (Weeks 24-104) | Personal Circumstance | 1 | 0 |
| Phase B (Weeks 24-104) | Physician Decision | 3 | 0 |
| Phase B (Weeks 24-104) | Protocol-Specific discontinuation | 5 | 3 |
| Phase B (Weeks 24-104) | Protocol-Specific lab discon criteria | 36 | 10 |
| Phase B (Weeks 24-104) | Protocol Violation | 1 | 0 |
| Phase B (Weeks 24-104) | Withdrawal by Subject | 15 | 5 |
Baseline characteristics
| Characteristic | Placebo / Glipizide 5 mg | Total | Sitagliptin 100 mg |
|---|---|---|---|
| Age, Continuous | 54.7 years STANDARD_DEVIATION 9.7 | 54.5 years STANDARD_DEVIATION 10.2 | 54.4 years STANDARD_DEVIATION 10.4 |
| Fasting Plasma Glucose (FPG) | 174.1 mg/dL STANDARD_DEVIATION 42 | 171.5 mg/dL STANDARD_DEVIATION 41.3 | 170.2 mg/dL STANDARD_DEVIATION 40.2 |
| Hemoglobin A1C (A1C) | 8.0 Percent STANDARD_DEVIATION 0.8 | 8.0 Percent STANDARD_DEVIATION 0.8 | 8.0 Percent STANDARD_DEVIATION 0.8 |
| Race/Ethnicity, Customized Asian | 26 participants | 75 participants | 49 participants |
| Race/Ethnicity, Customized Black | 14 participants | 45 participants | 31 participants |
| Race/Ethnicity, Customized Hispanic | 28 participants | 100 participants | 72 participants |
| Race/Ethnicity, Customized Other | 10 participants | 29 participants | 19 participants |
| Race/Ethnicity, Customized White | 159 participants | 452 participants | 293 participants |
| Sex: Female, Male Female | 96 Participants | 301 Participants | 205 Participants |
| Sex: Female, Male Male | 141 Participants | 400 Participants | 259 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 210 / 464 | 124 / 237 |
| serious Total, serious adverse events | 54 / 464 | 21 / 237 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1C (A1C) at Week 24
A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and 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 non-baseline observed measurement was carried forward to Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in Hemoglobin A1C (A1C) at Week 24 | -0.67 Percent |
| Placebo / Glipizide 5 mg | Change From Baseline in Hemoglobin A1C (A1C) at Week 24 | -0.02 Percent |
p-value: <0.00195% CI: [-0.77, -0.53]ANCOVA
Secondary
Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24
Change from baseline at Week 24 is defined as PMG at Week 24 minus PMG at Week 0.
Time frame: Baseline and 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 non-baseline observed measurement was carried forward to Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | -62.0 mg/dL |
| Placebo / Glipizide 5 mg | Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | -11.4 mg/dL |
p-value: <0.00195% CI: [-60.5, -40.8]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Change from baseline at Week 24 is defined as FPG at Week 24 minus FPG at Week 0.
Time frame: Baseline and 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 non-baseline observed measurement was carried forward to Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -16.9 mg/dL |
| Placebo / Glipizide 5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | 8.5 mg/dL |
p-value: <0.00195% CI: [-31, -19.8]ANCOVA