Type 2 Diabetes Mellitus
Conditions
Brief summary
A study to evaluate the efficacy and safety of sitagliptin in comparison to a commonly used medication in patients with type 2 diabetes
Interventions
DRUGsitagliptin phosphate
(1) sitagliptin 100mg tablet once daily (q.d.) for a 24-wk treatment period
DRUGComparator: metformin hydrochloride
(4) Metformin 500mg tablets once daily (q.d.) 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
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * Patient has type 2 diabetes mellitus (T2DM) * Patient is inadequately controlled and not on treatment with insulin or oral antihyperglycemic therapy General
Exclusion criteria
* Patient has a history of type 1 diabetes mellitus or history of ketoacidosis * Patient was on antihyperglycemic therapy (insulin or oral) within the prior 4 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | Baseline and 24 weeks | 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 |
|---|---|
| Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Diarrhea | Baseline to Week 24 |
| Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Nausea | Baseline to Week 24 |
| Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Abdominal Pain | Baseline to Week 24 |
| Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Vomiting | Baseline to Week 24 |
Participant flow
Recruitment details
First patient In: 04-Apr-2007 Last Patient Last Visit: 25-Jul-2008 113 study centers worldwide
Pre-assignment details
Patients 18-78 years of age with Type 2 diabetes mellitus (T2DM) who were not on anti-hyperglycemic agents for at least 4 months (16 weeks) and with a hemoglobin A1c (HbA1c) of ≥ 6.5 and ≤9.0%
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 tablet of sitagliptin once daily. | 528 |
| Metformin The Metformin group includes data from patients randomized to receive treatment with metformin initiated at a dose of 1 tablet (500 mg) per day. Patients were then to be up-titrated over a maximum of 5 weeks to a total daily dose of 2 tablets twice daily (1000 mg b.i.d). | 522 |
| Total | 1,050 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 19 |
| Overall Study | Glycemic discontinuation criteria | 1 | 1 |
| Overall Study | Lack of Efficacy | 10 | 1 |
| Overall Study | Lost to Follow-up | 9 | 14 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Protocol Violation | 14 | 15 |
| Overall Study | Trial Terminated ( Site Closed) | 1 | 0 |
| Overall Study | Withdrawal by Subject | 16 | 23 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg | Total | Metformin |
|---|---|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 10.7 | 56.0 years STANDARD_DEVIATION 10.6 | 56.1 years STANDARD_DEVIATION 10.4 |
| Body Weight | 84.9 Kilograms STANDARD_DEVIATION 17.7 | 84.7 Kilograms STANDARD_DEVIATION 17.5 | 84.6 Kilograms STANDARD_DEVIATION 17.2 |
| Hemoglobin A1c (HbA1c) | 7.2 Percent STANDARD_DEVIATION 0.7 | 7.3 Percent STANDARD_DEVIATION 0.7 | 7.3 Percent STANDARD_DEVIATION 0.7 |
| Race/Ethnicity, Customized Asian | 64 participants | 126 participants | 62 participants |
| Race/Ethnicity, Customized Black | 24 participants | 43 participants | 19 participants |
| Race/Ethnicity, Customized Other | 43 participants | 89 participants | 46 participants |
| Race/Ethnicity, Customized White | 397 participants | 792 participants | 395 participants |
| Sex: Female, Male Female | 278 Participants | 566 Participants | 288 Participants |
| Sex: Female, Male Male | 250 Participants | 484 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / — | 57 / — |
| serious Total, serious adverse events | 10 / — | 8 / — |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) 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 24 weeks
Population: The per protocol population required that a patient had measurements both at baseline and at Week 24, and did not have any major protocol violations (e.g. drug compliance \<85%, addition of prohibited antihyperglycemic agent, incorrect double-blind study medication). No missing data were imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | -0.43 Percent |
| Metformin | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 | -0.57 Percent |
95% CI: [0.06, 0.21]
Secondary
Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Abdominal Pain
Time frame: Baseline to Week 24
Population: All randomized patients who received at least 1 dose of the double-blind study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Abdominal Pain | Patients Who Reported Abdominal Pain | 11 Participants |
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Abdominal Pain | Patients Who Did Not Report Abdominal Pain | 517 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Abdominal Pain | Patients Who Reported Abdominal Pain | 20 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Abdominal Pain | Patients Who Did Not Report Abdominal Pain | 502 Participants |
p-value: 0.10395% CI: [-4, 0.3]Fisher Exact
Secondary
Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Diarrhea
Time frame: Baseline to Week 24
Population: All randomized patients who received at least 1 dose of the double-blind study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Diarrhea | Patients Who Reported Diarrhea | 19 Participants |
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Diarrhea | Patients Who Did Not Report Diarrhea | 509 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Diarrhea | Patients Who Reported Diarrhea | 57 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Diarrhea | Patients Who Did Not Report Diarrhea | 465 Participants |
p-value: <0.00195% CI: [-10.6, -4.2]Fisher Exact
Secondary
Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Nausea
Time frame: Baseline to Week 24
Population: All randomized patients who received at least 1 dose of the double-blind study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Nausea | Patients Who Reported Nausea | 6 Participants |
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Nausea | Patients Who Did Not Report Nausea | 522 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Nausea | Patients Who Reported Nausea | 16 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Nausea | Patients Who Did Not Report Nausea | 506 Participants |
p-value: 0.03295% CI: [-3.9, -0.2]Fisher Exact
Secondary
Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Vomiting
Time frame: Baseline to Week 24
Population: All randomized patients who received at least 1 dose of the double-blind study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Vomiting | Patients Who Reported Vomiting | 2 Participants |
| Sitagliptin 100 mg | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Vomiting | Patients Who Did Not Report Vomiting | 526 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Vomiting | Patients Who Reported Vomiting | 7 Participants |
| Metformin | Number of Patients Who Reported 1 or More Episodes of the Adverse Experience of Vomiting | Patients Who Did Not Report Vomiting | 515 Participants |
95% CI: [-2.4, 0.2]