Type 2 Diabetes Mellitus, Non Insulin Dependent, Diabetes Mellitus, Non-Insulin-Dependent
Conditions
Keywords
Type 2 Diabetes Mellitus, Non Insulin Dependent
Brief summary
A study to see if better control of type 2 diabetes can occur in patients taking a stable dose of metformin when they are also provided either sitagliptin or glimepiride. This study will also see if this treatment is safe and tolerable.
Interventions
DRUGsitagliptin
Sitagliptin 100 mg q.d. (q.d. = once daily); Duration of Treatment: 30 weeks
glimepiride 1 mg per day to be up-titrated (up to week 18 of the double-blind treatment period) as considered appropriate by the investigator, based upon the results of patient's self blood glucose monitoring (SBGM). The maximum dose of glimepiride must not be higher than 6 mg/day.
open-label metformin oral tablets (≥1500 mg/day) in addition to Glimepiride or Sitagliptin treatment.
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
* 18 years or older * Diagnosed with type 2 diabetes * On a stable dose of metformin of at least 1500 mg per day
Exclusion criteria
* History of type 1 diabetes * Pregnant * HIV positive * On a weight loss program or medication * Has a history of blood disorder, certain cancers, heart, liver or kidney disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at Week 30 | Week 0 to Week 30 | Patient-level HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the Week 0 HbA1c percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 30 | Week 0 to Week 30 | Change from baseline at Week 30 was defined as Week 30 minus Week 0. |
| Percent of Patients With at Least One Hypoglycemia Episode of Any Type at Week 30 | Week 0 to Week 30 | — |
| Change From Baseline in Body Weight at Week 30 | Week 0 to Week 30 | Change from baseline at Week 30 was defined as Week 30 minus Week 0. |
| Percent of Patients With A1C <7.0% at Week 30 | Week 30 | — |
| Percent of Patients With A1C <6.5% at Week 30 | Week 30 | — |
Participant flow
Recruitment details
Phase III First Patient In: 14-May-2008; Last Patient Last Visit: 27-Oct-2009; 109 study centers worldwide
Pre-assignment details
Patients at least 18 years of age with type 2 diabetes mellitus with inadequate glycemic control (A1C ≥6.5 and ≤9.0%) on a stable dose of metformin (at a dose of at least 1500 mg per day for at least 12 weeks) were eligible to enter the 30 week study. Up to a 2 week screening period, followed by a 2-week placebo run-in.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 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 open-label metformin oral tablets (≥1500 mg/day). | 516 |
| Glimepiride The Glimepiride group includes data from patients randomized to receive treatment starting with 1 mg oral tablets of glimepiride (blinded) up-titrated until Week 18 as needed to a maximum dose of 6 mg q.d. in addition to ongoing treatment with open-label metformin oral tablets (≥1500 mg/day). | 519 |
| Total | 1,035 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 5 | 4 |
| Overall Study | Lost to Follow-up | 9 | 9 |
| Overall Study | Other | 7 | 12 |
| Overall Study | Physician Decision | 3 | 4 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrawal by Subject | 11 | 16 |
Baseline characteristics
| Characteristic | Total | Glimepiride | Sitagliptin |
|---|---|---|---|
| A1C (Hemoglobin A1c) | 7.50 Percent STANDARD_DEVIATION 0.73 | 7.51 Percent STANDARD_DEVIATION 0.76 | 7.50 Percent STANDARD_DEVIATION 0.7 |
| Age, Continuous | 56.3 years STANDARD_DEVIATION 9.9 | 56.2 years STANDARD_DEVIATION 10.1 | 56.3 years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity, Customized American Indian/Alaska Native | 51 participants | 26 participants | 25 participants |
| Race/Ethnicity, Customized Asian | 220 participants | 111 participants | 109 participants |
| Race/Ethnicity, Customized Black | 12 participants | 6 participants | 6 participants |
| Race/Ethnicity, Customized Other | 157 participants | 78 participants | 79 participants |
| Race/Ethnicity, Customized White | 595 participants | 298 participants | 297 participants |
| Sex: Female, Male Female | 472 Participants | 240 Participants | 232 Participants |
| Sex: Female, Male Male | 563 Participants | 279 Participants | 284 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 519 | 134 / 518 |
| serious Total, serious adverse events | 16 / 516 | 11 / 518 |
Outcome results
Primary
Change From Baseline in HbA1c at Week 30
Patient-level HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Week 0 to Week 30
Population: The per protocol population included all patients with a baseline value, a measurement at Week 30, and no major protocol violations (i.e., drug compliance \<85%, use of prohibited medications, change of Metformin dose, incorrect double-blind study medication).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in HbA1c at Week 30 | -0.47 Percent |
| Glimepiride | Change From Baseline in HbA1c at Week 30 | -0.54 Percent |
95% CI: [-0.03, 0.16]
Secondary
Change From Baseline in Body Weight at Week 30
Change from baseline at Week 30 was defined as Week 30 minus Week 0.
Time frame: Week 0 to Week 30
Population: All patients who took at least one dose of study therapy and had body weight measurements at both baseline and Week 30.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in Body Weight at Week 30 | -0.8 Kilograms |
| Glimepiride | Change From Baseline in Body Weight at Week 30 | 1.2 Kilograms |
p-value: <0.00195% CI: [-2.3, -1.6]ANCOVA
Secondary
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 30
Change from baseline at Week 30 was defined as Week 30 minus Week 0.
Time frame: Week 0 to Week 30
Population: The per protocol population included all patients with a baseline value, a measurement at Week 30, and no major protocol violations (i.e., drug compliance \<85%, use of prohibited medications, change of Metformin dose, incorrect double-blind study medication).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 30 | -14.6 mg/dL |
| Glimepiride | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 30 | -17.5 mg/dL |
95% CI: [-0.9, 6.7]
Secondary
Percent of Patients With A1C <6.5% at Week 30
Time frame: Week 30
Population: The per protocol population included all patients with a baseline value, a measurement at Week 30, and no major protocol violations (i.e., drug compliance \<85%, use of prohibited medications, change of Metformin dose, incorrect double-blind study medication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percent of Patients With A1C <6.5% at Week 30 | 21.2 Percentage of Participants |
| Glimepiride | Percent of Patients With A1C <6.5% at Week 30 | 27.5 Percentage of Participants |
95% CI: [0.47, 0.95]
Secondary
Percent of Patients With A1C <7.0% at Week 30
Time frame: Week 30
Population: The per protocol population included all patients with a baseline value, a measurement at Week 30, and no major protocol violations (i.e., drug compliance \<85%, use of prohibited medications, change of Metformin dose, incorrect double-blind study medication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percent of Patients With A1C <7.0% at Week 30 | 52.4 Percentage of Participants |
| Glimepiride | Percent of Patients With A1C <7.0% at Week 30 | 59.6 Percentage of Participants |
95% CI: [0.47, 0.9]
Secondary
Percent of Patients With at Least One Hypoglycemia Episode of Any Type at Week 30
Time frame: Week 0 to Week 30
Population: All patients who took at least one dose of study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percent of Patients With at Least One Hypoglycemia Episode of Any Type at Week 30 | 7.0 Percentage of Participants |
| Glimepiride | Percent of Patients With at Least One Hypoglycemia Episode of Any Type at Week 30 | 22.0 Percentage of Participants |
p-value: <0.00195% CI: [-19.3, -10.9]Miettinen &Nurminen method