Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to determine the safety and efficacy of an investigational drug in patients with type 2 diabetes mellitus.
Interventions
Sitagliptin 100 mg once daily, from Visit 4 through Visit 8. Day 1 through week 24
DRUGComparator: Placebo
Placebo (to match Sitagliptin 100 mg) once daily, from Visit 4 through Visit 8. Day 1 through Week 24
Pioglitazone 30 mg or 45 mg once daily, Visit 2 through Visit 8
DRUGMetformin
Metformin rescue for patients meeting pre-specified glycemic criteria. Metformin 500 mg,once daily, Visit 4 through Visit 8
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
* Patient has type 2 diabetes mellitus (T2DM) * Patient is 18 years of age (or older) * Patient is not pregnant or breast-feeding and does not plan to become pregnant for the duration of the study and poststudy follow-up period
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis * Patient required insulin within the prior 8 weeks * Patient is on a weight loss program and is not in the maintenance phase * Patient started on a weight loss medication (e.g., orlistat or sibutramine) within the prior 8 weeks * Patient is on or likely to require treatment with treatment with immunosuppressive agents (e.g., cyclosporin, methotrexate) * Patient has cirrhosis, active liver disease (other than fatty liver) or symptomatic gallbladder disease * Patient has chronic myopathy, or a progressive neurological or neuromuscular disorder (e.g., multiple sclerosis or polymyositis) * Patient has any of the following disorders within the past 6 months: Acute coronary syndrome (e.g., MI or unstable angina), Coronary artery intervention, Stroke or transient ischemic neurological disorder. * Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months * Patient has severe peripheral vascular disease * Patient has congestive heart failure * Patient is HIV positive * Patient has a clinically important hematological disorder (e.g., aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) * Patient has a history of neoplastic disease * Patient has a history of alcohol or drug abuse within the past 3 years * Patient has viral hepatitis (hepatitis B or C)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | Baseline and week 24 | HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. |
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. |
Participant flow
Recruitment details
First Patient In: 15-Jul-2004. Last Patient Last Visit: 28-Sep-2005 71 study centers worldwide
Pre-assignment details
Patients ≥18 years of age with type 2 diabetes mellitus and inadequate glycemic control \[hemoglobin A1C (HbA1c) ≥7.0 and ≤10.0%\] who were on a stable dose of pioglitazone (≥30 mg/day) after a variable screening period were eligible to enter the 24-week study.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg The Sitagliptin 100 mg 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 pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day). | 175 |
| Placebo The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day). | 178 |
| Total | 353 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Patient Accidentally Unblinded | 1 | 0 |
| Overall Study | Patient Moved | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Discontinuation Criteria | 1 | 3 |
| Overall Study | Protocol Violation | 3 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 10.4 | 56.9 years STANDARD_DEVIATION 11.1 | 56.2 years STANDARD_DEVIATION 10.8 |
| HbA1c (Hemoglobin A1c) | 8.1 Percent STANDARD_DEVIATION 0.8 | 8.0 Percent STANDARD_DEVIATION 0.8 | 8.0 Percent STANDARD_DEVIATION 0.8 |
| Race/Ethnicity, Customized Asian | 10 participants | 5 participants | 15 participants |
| Race/Ethnicity, Customized Black | 11 participants | 12 participants | 23 participants |
| Race/Ethnicity, Customized Hispanic | 21 participants | 22 participants | 43 participants |
| Race/Ethnicity, Customized Other | 6 participants | 10 participants | 16 participants |
| Race/Ethnicity, Customized White | 127 participants | 129 participants | 256 participants |
| Sex: Female, Male Female | 82 Participants | 75 Participants | 157 Participants |
| Sex: Female, Male Male | 93 Participants | 103 Participants | 196 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 175 | 13 / 178 |
| serious Total, serious adverse events | 5 / 175 | 8 / 178 |
Outcome results
Primary
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c 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 | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -0.85 Percent |
| Placebo | Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | -0.15 Percent |
p-value: <0.00195% CI: [-0.85, -0.54]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. 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 | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | -16.7 mg/dL |
| Placebo | Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | 1.0 mg/dL |
p-value: <0.00195% CI: [-24.3, -11]ANCOVA