Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of an investigational treatment for type 2 diabetes mellitus.
Interventions
sitagliptin/Metformin HCl 50/500 mg tablet bid, titrating up to sitagliptin/Metformin HCl 50/1000 mg tablet over 4 weeks; for a 44-wk treatment period.
DRUGmetformin
metformin 500 mg tablet bid, titrating up to 1000 mg tablets bid for a 44-wk treatment period
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
* Patient has type 2 diabetes mellitus * Patient is greater than or equal to 18 and less than or equal to 78 years of age on the day of signing the consent * Patient has Hb1Ac greater than or equal to 7.5% and is appropriate for oral therapy * Patient has not been on any antihyperglycemic agent (AHA) in the last 4 months * Patient is a male, or a female who is unlikely to conceive
Exclusion criteria
* Patient has type 1 diabetes mellitus or history of ketoacidosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (A1C) at Week 18 | Baseline and Week 18 | A1C is measured as percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With A1C < 7.0% at Week 18 | Week 18 | — |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 | Baseline and Week 18 | FPG is measured as mg/dL. Thus, this change from baseline reflects the Week 18 FPG mg/dL minus the Week 0 FPG mg/dL. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 44 | Baseline and Week 44 | A1C is measured as percent. Thus, this change from baseline reflects the Week 44 A1C percent minus the Week 0 A1C percent. |
| Number of Patients With A1C < 7.0% at Week 44 | Week 44 | — |
Participant flow
Recruitment details
First Patient In: 26-Jun-2007; Last Patient Last Visit for end of study: 28-Apr-2009; Two-hundred four medical clinics in the United States (US) and 5 in Puerto Rico.
Pre-assignment details
Patients 18-78 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control (hemoglobin A1c \[A1C\] \>7.5% at screening visit) who were appropriate for treatment with oral antihyperglycemic therapy and had not been on an anti-hyperglycemic agent (AHA) in the last 4 months were eligible to participate.
Participants by arm
| Arm | Count |
|---|---|
| Sita/Met FDC The Sitagliptin/Metformin Fixed Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met initiated at a dose of 50/500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated. | 625 |
| Metformin The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated. | 621 |
| Total | 1,246 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 29 | 33 |
| Overall Study | Creatinine/Creatinine Clearance Criteria | 0 | 2 |
| Overall Study | Hyperglycemia Criteria | 7 | 5 |
| Overall Study | Lack of Efficacy | 4 | 16 |
| Overall Study | Lost to Follow-up | 86 | 66 |
| Overall Study | Physician Decision | 10 | 7 |
| Overall Study | Pregnancy | 4 | 2 |
| Overall Study | Protocol Violation | 10 | 18 |
| Overall Study | Withdrawal by Subject | 67 | 69 |
Baseline characteristics
| Characteristic | Sita/Met FDC | Metformin | Total |
|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 10.5 | 50.0 years STANDARD_DEVIATION 10.5 | 49.7 years STANDARD_DEVIATION 10.5 |
| Hemoglobin A1c (A1C) | 9.91 Percent STANDARD_DEVIATION 1.83 | 9.83 Percent STANDARD_DEVIATION 1.77 | 9.87 Percent STANDARD_DEVIATION 1.8 |
| Race/Ethnicity, Customized Asian | 17 Participants | 24 Participants | 41 Participants |
| Race/Ethnicity, Customized Black | 82 Participants | 88 Participants | 170 Participants |
| Race/Ethnicity, Customized Other | 18 Participants | 20 Participants | 38 Participants |
| Race/Ethnicity, Customized White | 508 Participants | 489 Participants | 997 Participants |
| Sex: Female, Male Female | 272 Participants | 266 Participants | 538 Participants |
| Sex: Female, Male Male | 353 Participants | 355 Participants | 708 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 173 / 625 | 185 / 621 |
| serious Total, serious adverse events | 28 / 625 | 38 / 621 |
Outcome results
Primary
Change From Baseline in 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.
Time frame: Baseline and Week 18
Population: The Full Analysis Set (FAS) included all patients who received at least 1 dose of double-blind study therapy, had a baseline value and ≥ 1 post-baseline value for this outcome. Data after initiation of additional AHA were treated as missing. For FAS with no data at Week 18, the last post-baseline observed measurement was carried forward to Week 18.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change From Baseline in Hemoglobin A1c (A1C) at Week 18 | -2.37 Percent |
| Metformin | Change From Baseline in Hemoglobin A1c (A1C) at Week 18 | -1.76 Percent |
p-value: <0.00195% CI: [-0.78, -0.43]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18
FPG is measured as mg/dL. Thus, this change from baseline reflects the Week 18 FPG mg/dL minus the Week 0 FPG mg/dL.
Time frame: Baseline and Week 18
Population: The Full Analysis Set (FAS) included all patients who received at least 1dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were treated as missing. For FAS with no data at Week 18, the last post-baseline observed measurement was carried forward to Week 18.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 | -69.4 mg/dL |
| Metformin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 | -53.7 mg/dL |
p-value: <0.00195% CI: [-22.4, -9]ANCOVA
Secondary
Number of Patients With A1C < 7.0% at Week 18
Time frame: Week 18
Population: The Full Analysis Set (FAS) included all patients who received at least 1 dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were treated as missing. For FAS with no data at Week 18, the last post-baseline observed measurement was carried forward to Week 18.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sita/Met FDC | Number of Patients With A1C < 7.0% at Week 18 | Patients with A1C <7.0% at Week 18 | 275 Participants |
| Sita/Met FDC | Number of Patients With A1C < 7.0% at Week 18 | Patients with A1C ≥7.0% at Week 18 | 284 Participants |
| Metformin | Number of Patients With A1C < 7.0% at Week 18 | Patients with A1C <7.0% at Week 18 | 193 Participants |
| Metformin | Number of Patients With A1C < 7.0% at Week 18 | Patients with A1C ≥7.0% at Week 18 | 371 Participants |
p-value: <0.00195% CI: [1.6, 2.69]ANCOVA
Other Pre-specified
Change From Baseline in A1C at Week 44
A1C is measured as percent. Thus, this change from baseline reflects the Week 44 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and Week 44
Population: The Full Analysis Set (FAS) included all patients who received at least 1 dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were included. For FAS with no data at Week 44, the last post-baseline observed measurement was carried forward to Week 44.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sita/Met FDC | Change From Baseline in A1C at Week 44 | -2.25 Percent |
| Metformin | Change From Baseline in A1C at Week 44 | -1.77 Percent |
95% CI: [-0.67, -0.3]
Other Pre-specified
Number of Patients With A1C < 7.0% at Week 44
Time frame: Week 44
Population: The Full Analysis Set (FAS) included all patients who received at least 1dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were included. For FAS with no data at Week 44, the last post-baseline observed measurement was carried forward to Week 44.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sita/Met FDC | Number of Patients With A1C < 7.0% at Week 44 | Patients with A1C <7.0% at Week 44 | 258 Participants |
| Sita/Met FDC | Number of Patients With A1C < 7.0% at Week 44 | Patients with A1C ≥7.0% at Week 44 | 302 Participants |
| Metformin | Number of Patients With A1C < 7.0% at Week 44 | Patients with A1C <7.0% at Week 44 | 173 Participants |
| Metformin | Number of Patients With A1C < 7.0% at Week 44 | Patients with A1C ≥7.0% at Week 44 | 396 Participants |
95% CI: [1.63, 2.73]