Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to test the safety and effectiveness of sitagliptin in patients with type 2 diabetes.
Interventions
DRUGSitagliptin
Sitagliptin 100 mg administered as one oral tablet once daily in the morning for up to 18 weeks.
DRUGComparator: Rosiglitazone
Rosiglitazone 8 mg administered as two 4 mg capsules once daily in the morning for up to 18 weeks.
DRUGComparator: Placebo
placebo - administered as one placebo tablet to match Sitagliptin 100 mg and two placebo capsules to match rosiglitazone 4 mg once daily in the morning for up to 18 weeks.
Open-label metformin was supplied by the Sponsor as 500, 850, or 1000 mg oral tablets administered at a daily dose of \>= 1500 mg.
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 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Patient has Type 2 diabetes * Currently taking metformin \>1500 mg/day for at least 10 weeks * Male or female
Exclusion criteria
* Patient has peripheral edema * History of type 1 diabetes * Patient required insulin within prior 8 weeks * Have participated or are currently participating in another study with an investigational compound or device within 12 weeks of starting this study * Participating in a weight loss program
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1C (A1C) at Week 18 | Baseline and 18 Weeks | A1C is measured as percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent. The study hypothesis comparison was between sitagliptin versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Plasma Glucose (FPG) at Week 18 | Baseline and 18 Weeks | The change from baseline is the Week 18 FPG minus the Week 0 FPG. |
| 2-hour Post-meal Glucose (PMG) at Week 18 | Baseline and 18 Weeks | The change from baseline is the Week 18 PMG minus the Week 0 PMG. |
Participant flow
Recruitment details
First Patient In: 16-June-2006. Last Patient Last Visit: 2-March-2007. 13 medical clinics in 3 countries in Europe and 23 in 4 countries in the rest of the world
Pre-assignment details
Patients 18-75 years of age with type 2 diabetes mellitus (T2DM) who were taking metformin monotherapy at a stable dose of ≥ 1500 mg/day for at least 10 weeks and had inadequate glycemic control (hemoglobin A1C ≥ 7.0% and ≤11%) 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 and placebo matching rosiglitazone q.d. (once-daily) with metformin (≥1500 mg/day). | 94 |
| Rosiglitazone The Rosiglitazone group includes data from patients randomized to receive treatment with oral tablets of rosiglitazone 8 mg and placebo matching sitagliptin q.d. in combination with metformin (≥1500 mg/day). | 87 |
| Placebo The Placebo group includes data from patients randomized to receive treatment with oral tablets of placebo matching sitagliptin and placebo matching rosiglitazone q.d. with metformin (≥1500 mg/day). | 92 |
| Total | 273 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject and Other | 5 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Sitagliptin | Rosiglitazone | Placebo |
|---|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 9.8 | 55.2 years STANDARD_DEVIATION 9.8 | 54.8 years STANDARD_DEVIATION 10.5 | 55.3 years STANDARD_DEVIATION 9.3 |
| Fasting Plasma Glucose (FPG) | 158.1 mg/dL STANDARD_DEVIATION 33.5 | 157.5 mg/dL STANDARD_DEVIATION 31.4 | 156.9 mg/dL STANDARD_DEVIATION 31.6 | 160.0 mg/dL STANDARD_DEVIATION 37.4 |
| Hemoglobin A1C (A1C) | 7.7 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 0.9 | 7.8 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 1 | 7.7 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 0.8 | 7.7 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 0.9 |
| Race/Ethnicity, Customized Asian | 105 participants | 36 participants | 33 participants | 36 participants |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 3 participants | 1 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized White | 164 participants | 57 participants | 51 participants | 56 participants |
| Sex: Female, Male Female | 112 Participants | 42 Participants | 32 Participants | 38 Participants |
| Sex: Female, Male Male | 161 Participants | 52 Participants | 55 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 94 | 1 / 87 | 0 / 91 |
| serious Total, serious adverse events | 5 / 94 | 5 / 87 | 5 / 91 |
Outcome results
Primary
Hemoglobin A1C (A1C) at Week 18
A1C is measured as percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent. The study hypothesis comparison was between sitagliptin versus placebo.
Time frame: Baseline and 18 Weeks
Population: The all patients treated population included all patients who took at least one dose of study medication and had both a baseline measurement and at least one post-randomization measurement for this outcome. Missing data were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Hemoglobin A1C (A1C) at Week 18 | -0.73 Percent of glycosylated hemoglobin (A1C) |
| Rosiglitazone | Hemoglobin A1C (A1C) at Week 18 | -0.79 Percent of glycosylated hemoglobin (A1C) |
| Placebo | Hemoglobin A1C (A1C) at Week 18 | -0.22 Percent of glycosylated hemoglobin (A1C) |
p-value: <=0.00195% CI: [-0.7, -0.32]ANCOVA
Secondary
2-hour Post-meal Glucose (PMG) at Week 18
The change from baseline is the Week 18 PMG minus the Week 0 PMG.
Time frame: Baseline and 18 Weeks
Population: The all patients treated population included all patients who took at least one dose of study medication and had both a baseline measurement and at least one post-randomization measurement for this outcome. Missing data were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | 2-hour Post-meal Glucose (PMG) at Week 18 | -35.4 mg/dL |
| Rosiglitazone | 2-hour Post-meal Glucose (PMG) at Week 18 | -51.3 mg/dL |
| Placebo | 2-hour Post-meal Glucose (PMG) at Week 18 | -4.9 mg/dL |
p-value: <=0.00195% CI: [-46, -15]ANCOVA
Secondary
Fasting Plasma Glucose (FPG) at Week 18
The change from baseline is the Week 18 FPG minus the Week 0 FPG.
Time frame: Baseline and 18 Weeks
Population: The all patients treated population included all patients who took at least one dose of study medication and had both a baseline measurement and at least one post-randomization measurement for this outcome. Missing data were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Fasting Plasma Glucose (FPG) at Week 18 | -11.7 mg/dL |
| Rosiglitazone | Fasting Plasma Glucose (FPG) at Week 18 | -24.5 mg/dL |
| Placebo | Fasting Plasma Glucose (FPG) at Week 18 | 6.1 mg/dL |
p-value: <=0.00195% CI: [-27.6, -8.1]ANCOVA