Type 2 Diabetes
Conditions
Brief summary
To evaluate the effect of treatment with sitagliptin compared to placebo in elderly patients with type 2 diabetes mellitus who have poor glycemic control with diet and exercise.
Interventions
DRUGsitagliptin phosphate
Once daily (q.d.) administration of sitagliptin 100 mg tablet (or 50 mg based on creatinine clearance). For up to a 24-wk treatment period.
DRUGComparator: Placebo
sitagliptin matching placebo for up to 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
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Community dwelling patients 65 years of age or older diagnosed with Type 2 Diabetes not controlled with diet and exercise * Patients must have a HbA1c of 7-10% off medication, or as a result of a protocol wash-out from oral anti-hyperglycemic agents by the qualifying visit
Exclusion criteria
* Patients with type 1 diabetes * History of ketoacidosis or requires insulin use * Alanine aminotransferase / aspartate aminotransferase \> 2.5 X ULN, triglycerides \> 600 mg/dL, creatinine clearance \< 35 mL/min * Fasting plasma glucose consistently \> 260 mg/dL * Poorly controlled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Hemoglobin A1c) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. |
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. |
| Rapidity of Onset of Action as Determined by Home Glucose Monitoring After 1 Week | Week 1 | Fingerstick glucose measurements were taken at 4 times (pre- and 2 hours post-breakfast and dinner) at each of Days -2, 3, and 7. The average of the 4 values was computed for each day. This outcome reflects the Day 7 average minus the Day -2 average. |
Participant flow
Recruitment details
First Patient In: 30-MAR-2006 Last Patient Last Visit: 12-MAR-2008 60 medical clinics in the United States.
Pre-assignment details
Community dwelling patients ≥ 65 years of age with a diagnosis of type 2 diabetes with hemoglobin A1c (HbA1c) ≥ 7% and ≤ 10% on diet and exercise were eligible to participate. Following a variable duration screening period, patients were randomized in a 1:1 ratio to sitagliptin 100 mg q.d. (or 50 mg q.d. based on creatinine clearance) and placebo.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Once-daily administration of sitagliptin 100 mg (or 50 mg based on creatinine clearance); Patients may be down-titrated (1 instead of 2 tablets) if there is a decrease in creatinine clearance to \< 50 mL/min at any time during the study. | 102 |
| Placebo Sitagliptin-matching placebo tablets. | 104 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Lack of Efficacy | 11 | 18 |
| Overall Study | Lost to Follow-up | 0 | 4 |
| Overall Study | Patient moved | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 12 | 21 |
Baseline characteristics
| Characteristic | Sitagliptin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 6.1 | 72.1 years STANDARD_DEVIATION 6 | 71.9 years STANDARD_DEVIATION 6 |
| HbA1c (Hemoglobin A1c) | 7.8 Percent STANDARD_DEVIATION 0.8 | 7.8 Percent STANDARD_DEVIATION 0.7 | 7.8 Percent STANDARD_DEVIATION 0.7 |
| Race/Ethnicity, Customized Asian | 3 participants | 3 participants | 6 participants |
| Race/Ethnicity, Customized Black | 10 participants | 9 participants | 19 participants |
| Race/Ethnicity, Customized Hispanic | 9 participants | 6 participants | 15 participants |
| Race/Ethnicity, Customized Other | 4 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized White | 76 participants | 86 participants | 162 participants |
| Sex: Female, Male Female | 54 Participants | 55 Participants | 109 Participants |
| Sex: Female, Male Male | 48 Participants | 49 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / — | 6 / — |
| serious Total, serious adverse events | 7 / — | 14 / — |
Outcome results
Primary
Change From Baseline in HbA1c (Hemoglobin A1c) 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 | Change From Baseline in HbA1c (Hemoglobin A1c) at Week 24 | -0.47 Percent |
| Placebo | Change From Baseline in HbA1c (Hemoglobin A1c) at Week 24 | 0.23 Percent |
p-value: <0.00195% CI: [-0.94, -0.47]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 | Change From Baseline in 2-hour PPG (Post-prandial Glucose) at Week 24 | -52.1 mg/dL |
| Placebo | Change From Baseline in 2-hour PPG (Post-prandial Glucose) at Week 24 | 8.9 mg/dL |
p-value: <0.00195% CI: [-82.1, -40]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 | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -16.2 mg/dL |
| Placebo | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | 10.6 mg/dL |
p-value: <0.00195% CI: [-40, -13.5]ANCOVA
Secondary
Rapidity of Onset of Action as Determined by Home Glucose Monitoring After 1 Week
Fingerstick glucose measurements were taken at 4 times (pre- and 2 hours post-breakfast and dinner) at each of Days -2, 3, and 7. The average of the 4 values was computed for each day. This outcome reflects the Day 7 average minus the Day -2 average.
Time frame: Week 1
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 Day 7, the last observed measurement was carried forward to Day 7. Patients had the option to participate in self monitoring of glucose.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Rapidity of Onset of Action as Determined by Home Glucose Monitoring After 1 Week | -25.7 mg/dL |
| Placebo | Rapidity of Onset of Action as Determined by Home Glucose Monitoring After 1 Week | -2.1 mg/dL |
p-value: <0.00195% CI: [-32.6, -14.4]ANCOVA