Type 2 Diabetes Mellitus
Conditions
Brief summary
A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on insulin or insulin/metformin combination therapy.
Interventions
DRUGsitagliptin phosphate
sitagliptin 100 mg tablet qd for a 24-wk treatment period.
sitagliptin 100 mg Pbo tablet qd for a 24-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
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has type 2 diabetes mellitus * Patient is poorly controlled while on insulin or insulin and metformin
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or history of ketoacidosis * Patient is taking oral antidiabetic agents other than metformin during the past 3 months * Patient is currently on treatment with daily use of pre-prandial short-acting or rapid-acting insulin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 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 Week 24 minus 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 Week 24 minus Week 0. |
| Percent of Patients With A1C < 7.0% at Week 24 | 24 Weeks | — |
| Percent of Patients With A1C < 6.5% at Week 24 | Week 24 | — |
| Percent Change From Baseline in Index of Static Beta-Cell Sensitivity to Glucose at Week 24 | Baseline and Week 24 | Static sensitivity is a measure of the effect of glucose on beta-cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. (See Breda and Cobelli, Annals of Biomedical Engineering 29, 692-700 (2001) for more details.) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 24 | Baseline and Week 24 | A1C in subset of patients on long-acting or intermediate-acting insulin. A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. |
Participant flow
Recruitment details
Phase III First Patient In: 29-Jan-2007 Last Patient Last Visit: 13-Oct-2008; 100 study centers worldwide
Pre-assignment details
Patients at least 21 years of age with type 2 diabetes mellitus with inadequate glycemic control (A1C ≥7.5 and ≤11.0%) on stable-dose insulin (alone or in combination with stable-dose metformin) were eligible to enter the 24 week study. 1-week screening, followed by a 2-week single-blind placebo run-in.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg q.d. The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day). | 322 |
| Placebo The Placebo group includes data from patients randomized to receive treatment with a placebo of the sitagliptin 100 mg oral tablet once daily (blinded) in addition to ongoing treatment with insulin (pre-mixed, intermediate-acting, or long-acting) alone or in combination with open-label metformin 500 mg oral tablets (≥1500 mg/day). | 319 |
| Total | 641 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 5 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Other | 5 | 2 |
| Overall Study | Physician Decision | 2 | 4 |
| Overall Study | Protocol Violation | 6 | 8 |
| Overall Study | Withdrawal by Subject | 11 | 12 |
Baseline characteristics
| Characteristic | Total | Placebo | Sitagliptin 100 mg q.d. |
|---|---|---|---|
| A1C (Hemoglobin A1c) | 8.7 Percent STANDARD_DEVIATION 0.9 | 8.6 Percent STANDARD_DEVIATION 0.9 | 8.7 Percent STANDARD_DEVIATION 0.9 |
| Age, Continuous | 57.8 years STANDARD_DEVIATION 9.2 | 57.2 years STANDARD_DEVIATION 9.3 | 58.3 years STANDARD_DEVIATION 9.1 |
| Race/Ethnicity, Customized Asian | 116 participants | 61 participants | 55 participants |
| Race/Ethnicity, Customized Black | 44 participants | 23 participants | 21 participants |
| Race/Ethnicity, Customized Other | 34 participants | 16 participants | 18 participants |
| Race/Ethnicity, Customized White | 447 participants | 219 participants | 228 participants |
| Sex: Female, Male Female | 315 Participants | 150 Participants | 165 Participants |
| Sex: Female, Male Male | 326 Participants | 169 Participants | 157 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 49 / 322 | 25 / 319 |
| serious Total, serious adverse events | 20 / 322 | 11 / 319 |
Outcome results
Primary
Change From Baseline in 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 q.d. | Change From Baseline in A1C at Week 24 | -0.59 Percent |
| Placebo | Change From Baseline in A1C at Week 24 | -0.03 Percent |
p-value: <0.00195% CI: [-0.7, -0.42]ANCOVA
Secondary
Change From Baseline in 2-hour Post-meal Glucose (PMG) 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. 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 q.d. | Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | -30.9 mg/dL |
| Placebo | Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | 5.2 mg/dL |
p-value: <0.00195% CI: [-47.1, -25.1]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) 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. 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 q.d. | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -18.5 mg/dL |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -3.5 mg/dL |
p-value: <0.00195% CI: [-23.4, -6.5]ANCOVA
Secondary
Percent Change From Baseline in Index of Static Beta-Cell Sensitivity to Glucose at Week 24
Static sensitivity is a measure of the effect of glucose on beta-cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. (See Breda and Cobelli, Annals of Biomedical Engineering 29, 692-700 (2001) for more details.)
Time frame: Baseline and Week 24
Population: The Full Analysis Set (FAS) included all patients who participated in the 10-point meal tolerance test and had 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 q.d. | Percent Change From Baseline in Index of Static Beta-Cell Sensitivity to Glucose at Week 24 | 28.4 Percent |
| Placebo | Percent Change From Baseline in Index of Static Beta-Cell Sensitivity to Glucose at Week 24 | -8.1 Percent |
p-value: 0.0195% CI: [8.9, 64.7]ANCOVA
Secondary
Percent of Patients With A1C < 6.5% at Week 24
Time frame: 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 (NUMBER) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Percent of Patients With A1C < 6.5% at Week 24 | 2.3 Percent |
| Placebo | Percent of Patients With A1C < 6.5% at Week 24 | 1.9 Percent |
p-value: 0.58495% CI: [0.45, 4.18]Logistic Regression
Secondary
Percent of Patients With A1C < 7.0% at Week 24
Time frame: 24 Weeks
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 (NUMBER) |
|---|---|---|
| Sitagliptin 100 mg q.d. | Percent of Patients With A1C < 7.0% at Week 24 | 12.8 Percent |
| Placebo | Percent of Patients With A1C < 7.0% at Week 24 | 5.1 Percent |
p-value: <0.00195% CI: [1.89, 6.85]Logistic Regression
Other Pre-specified
Change From Baseline in A1C at Week 24
A1C in subset of patients on long-acting or intermediate-acting insulin. 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 the subset of patients on long-acting or intermediate-acting insulin 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 q.d. | Change From Baseline in A1C at Week 24 | -0.61 Percent |
| Placebo | Change From Baseline in A1C at Week 24 | -0.04 Percent |
p-value: <0.00195% CI: [-0.72, -0.4]ANCOVA