Type 2 Diabetes Mellitus
Conditions
Brief summary
A clinical study to evaluate the safety and efficacy of the initial combination therapy with sitagliptin and pioglitazone in patients with type 2 diabetes mellitus not on treatment with insulin or oral antihyperglycemic therapy.
Interventions
DRUGsitagliptin 100 mg q.d./pioglitazone 30 mg q.d
Patients will receive initial combination therapy with blinded sitagliptin 100 mg q.d. and open- label pioglitazone 30 mg q.d. for up to 24 Weeks. Sitagliptin 100 mg q.d. and pioglitazone 30 mg q.d. will be administered as oral tablets.
DRUGComparator: placebo to match sitagliptin 100 mg q.d./pioglitazone 30 mg q.d.
Patients will receive placebo to match sitagliptin 100 mg q.d. (blinded) and open label pioglitazone 30 mg q.d. for up to 24 Weeks. Placebo to match sitagliptin 100 mg q.d.(blinded) and open-label pioglitazone 30 mg q.d. will be administered as oral tablets.
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 No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * Patients ≥18 years old with Type 2 Diabetes Mellitus (a specific type of diabetes) General
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or history of ketoacidosis * Patient was on antihyperglycemic agent therapy (oral or insulin) within the prior 4 months * Patient was on \>4 weeks (cumulatively) of antihyperglycemic therapy (oral or insulin) over the prior 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | Baseline and 24 weeks | HbA1c is measured as a percent. Thus, 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 FPG (Fasting Plasma Glucose) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. |
| Change From Baseline in 2-hour PPG (Post-prandial Glucose) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. |
Participant flow
Recruitment details
First Patient In: 01-Feb-2007; Last Patient Last Visit: 28-Jun-2008; 60 study sites worldwide.
Pre-assignment details
Patients ≥18 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control (HbA1C ≥8% and ≤12%) on diet and exercise alone were eligible for randomization.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d. The Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive coadministration of sitagliptin 100 mg oral tablets and pioglitazone 30 mg oral tablets administered once daily. | 261 |
| Pioglitazone 30 mg q.d. The Pioglitazone 30 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive coadministration of pioglitazone 30 mg oral tablets and placebo to sitagliptin 100 mg oral tablets administered once daily. | 259 |
| Total | 520 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Lack of Efficacy | 7 | 10 |
| Overall Study | Lost to Follow-up | 8 | 9 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | protocol discontinuation criteria | 1 | 4 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 14 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d. | Pioglitazone 30 mg q.d. | Total |
|---|---|---|---|
| Age, Continuous | 50.2 years STANDARD_DEVIATION 10.2 | 51.6 years STANDARD_DEVIATION 11.2 | 50.9 years STANDARD_DEVIATION 10.7 |
| HbA1c (Hemoglobin A1C) | 9.5 Percent STANDARD_DEVIATION 1.2 | 9.5 Percent STANDARD_DEVIATION 1.2 | 9.5 Percent STANDARD_DEVIATION 1.2 |
| Race/Ethnicity, Customized Asian | 85 participants | 83 participants | 168 participants |
| Race/Ethnicity, Customized Black | 11 participants | 8 participants | 19 participants |
| Race/Ethnicity, Customized Other | 27 participants | 34 participants | 61 participants |
| Race/Ethnicity, Customized White | 138 participants | 134 participants | 272 participants |
| Sex: Female, Male Female | 124 Participants | 114 Participants | 238 Participants |
| Sex: Female, Male Male | 137 Participants | 145 Participants | 282 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / — | 25 / — |
| serious Total, serious adverse events | 8 / — | 5 / — |
Outcome results
Primary
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Baseline and 24 weeks
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. For FAS patients with no data at Week 24, the last observed measurement was carried forward to Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -2.38 Percent |
| Pioglitazone 30 mg q.d. | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -1.49 Percent |
p-value: <0.00195% CI: [-1.13, -0.65]ANCOVA
Secondary
Change From Baseline in 2-hour PPG (Post-prandial Glucose) at Week 24
Change from baseline at Week 24 is defined as Week 24 minus 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. For FAS patients with no data at Week 24, the last observed measurement was carried forward to Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d. | Change From Baseline in 2-hour PPG (Post-prandial Glucose) at Week 24 | -113.6 mg/dL |
| Pioglitazone 30 mg q.d. | Change From Baseline in 2-hour PPG (Post-prandial Glucose) at Week 24 | -68.9 mg/dL |
p-value: <0.00195% CI: [-57.2, 32.2]ANCOVA
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: 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. For FAS patients with no data at Week 24, the last observed measurement was carried forward to Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. + Pioglitazone 30 mg q.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -63.0 mg/dL |
| Pioglitazone 30 mg q.d. | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -40.2 mg/dL |
p-value: <0.00195% CI: [-30.4, -15.2]ANCOVA