Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this clinical study is to determine the safety and efficacy of an investigational drug in patients with Type 2 diabetes mellitus.
Interventions
sitagliptin 10 mg tablet, once daily for 54 weeks
DRUGComparator: Placebo
Placebo oral tablet once daily for 24 weeks
Pioglitazone 30 mg tablet once daily for 30 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with Type 2 Diabetes Mellitus with inadequate glycemic control
Exclusion criteria
* Patients with Type 1 Diabetes Mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 24 | Baseline and 24 Weeks | Hemoglobin A1C (A1C) is measured as 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 FPG at Week 24 | Baseline and 24 Weeks | The change from baseline is the Week 24 Fasting Plasma Glucose (FPG) minus the Week 0 FPG. |
Participant flow
Recruitment details
First Patient In: 27-Apr-2005. Last Patient Last Visit: 09-Jan-2007. 27 medical clinics in the United States (US), 25 in 11 countries in Europe, and 22 in 11 countries in the rest of the world.
Pre-assignment details
Patients 18-75 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control (hemoglobin A1c \[A1C\] ≥7.5% and ≤10.5%) at screening or after treatment with glimepiride (≥4 mg) alone or in combination with metformin (≥1500 mg) for a dose stable period of up to 10 weeks were eligible to participate.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin The Sitagliptin group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 100 mg q.d. (once daily) with glimepiride (≥4 mg/day) alone or in combination with metformin (≥1500 mg/day). | 222 |
| Placebo/ Pioglitazone The Placebo group includes data from patients randomized to receive treatment with placebo to sitagliptin oral tablets q.d. with glimepiride (≥4 mg/day) alone or in combination with metformin (≥1500 mg/day). | 219 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 7 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Laboratory test | 1 | 1 |
| Overall Study | Lack of Efficacy | 67 | 69 |
| Overall Study | Lost to Follow-up | 7 | 3 |
| Overall Study | Patient moved | 1 | 0 |
| Overall Study | Patient Received Glycemic Medication | 22 | 41 |
| Overall Study | Planned major surgery | 1 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 7 |
| Overall Study | Site terminated | 0 | 1 |
| Overall Study | Unable to re-enter US | 1 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 21 |
Baseline characteristics
| Characteristic | Placebo/ Pioglitazone | Total | Sitagliptin |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 9.6 | 56.0 years STANDARD_DEVIATION 9.6 | 55.6 years STANDARD_DEVIATION 9.6 |
| Fasting Plasma Glucose (FPG) | 181.6 mg/dL STANDARD_DEVIATION 42.5 | 181.2 mg/dL STANDARD_DEVIATION 40.1 | 180.9 mg/dL STANDARD_DEVIATION 37.7 |
| Hemoglobin A1C (A1C) | 8.34 Percent STANDARD_DEVIATION 0.74 | 8.34 Percent STANDARD_DEVIATION 0.75 | 8.34 Percent STANDARD_DEVIATION 0.76 |
| Race/Ethnicity, Customized Asian | 25 participants | 47 participants | 22 participants |
| Race/Ethnicity, Customized Black | 12 participants | 22 participants | 10 participants |
| Race/Ethnicity, Customized Hispanic | 32 participants | 71 participants | 39 participants |
| Race/Ethnicity, Customized Other | 10 participants | 25 participants | 15 participants |
| Race/Ethnicity, Customized White | 140 participants | 276 participants | 136 participants |
| Sex: Female, Male Female | 102 Participants | 207 Participants | 105 Participants |
| Sex: Female, Male Male | 117 Participants | 234 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 222 | 57 / 219 |
| serious Total, serious adverse events | 17 / 222 | 13 / 219 |
Outcome results
Primary
Change From Baseline in A1C at Week 24
Hemoglobin A1C (A1C) is measured as percent. Thus this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and 24 Weeks
Population: All Patients Treated included patients who received at least 1 dose of study therapy, and had a baseline value and ≥1 post-baseline value for this outcome. The last post-baseline observed measurement was carried forward to Week 24 for patients with no data at Week 24. Data obtained after glycemic rescue were considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in A1C at Week 24 | -0.45 Percent |
| Placebo/ Pioglitazone | Change From Baseline in A1C at Week 24 | 0.28 Percent |
p-value: <0.00195% CI: [-90, -0.57]ANCOVA
Secondary
Change From Baseline in FPG at Week 24
The change from baseline is the Week 24 Fasting Plasma Glucose (FPG) minus the Week 0 FPG.
Time frame: Baseline and 24 Weeks
Population: All Patients Treated included patients who received at least 1 dose of study therapy, and had a baseline value and ≥1 post-baseline value for this outcome. The last post-baseline observed measurement was carried forward to Week 24 for patients with no data at Week 24. Data after rescue were considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in FPG at Week 24 | -4.4 mg/dL |
| Placebo/ Pioglitazone | Change From Baseline in FPG at Week 24 | 15.7 mg/dL |
p-value: <0.00195% CI: [-28.4, -11.8]ANCOVA