Trial Outcomes & Findings for MK0431 (Sitagliptin) and Metformin Co-Administration Factorial Study in Patients With Type 2 Diabetes Mellitus (0431-036) (NCT NCT00103857)
NCT ID: NCT00103857
Last Updated: 2017-05-05
Results Overview
HbA1c is measured as a percent. This change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1208 participants
Primary outcome timeframe
Week 24
Results posted on
2017-05-05
Participant Flow
First Patient In: 01-Apr-2005 Last Patient Last Visit: 29-Feb-2008 140 study centers worldwide
Patients 18-78 years with T2DM and an HbA1c 7.5-11% on diet/exercise were eligible for randomization into the 54-week (wk) base study. Patients with an HbA1c \>11% or glucose \>280 mg/dL were eligible to participate in the Open-label Cohort through Wk 24. Randomized patients who completed the base study were eligible to enter a 50-wk extension study.
Participant milestones
| Measure |
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 two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
The Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) OLC (Open-label Cohort) includes data from non-randomized patients assigned to receive treatment with open-label, oral tablets of sitagliptin and metformin. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning on Day 1. The dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients continued to take open-label sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the Phase A treatment period of up to 24 weeks. Results presented for the OLC are through Week 24. Patients in the OLC completed the study at Week 24.
|
|---|---|---|---|---|---|---|---|
|
54-Week Base Study
STARTED
|
179
|
182
|
182
|
190
|
182
|
176
|
117
|
|
54-Week Base Study
COMPLETED
|
122
|
126
|
135
|
148
|
141
|
115
|
79
|
|
54-Week Base Study
NOT COMPLETED
|
57
|
56
|
47
|
42
|
41
|
61
|
38
|
|
50-Week Extension Study
STARTED
|
103
|
107
|
121
|
134
|
122
|
98
|
0
|
|
50-Week Extension Study
COMPLETED
|
65
|
80
|
95
|
98
|
101
|
78
|
0
|
|
50-Week Extension Study
NOT COMPLETED
|
38
|
27
|
26
|
36
|
21
|
20
|
0
|
Reasons for withdrawal
| Measure |
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 two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
The Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) OLC (Open-label Cohort) includes data from non-randomized patients assigned to receive treatment with open-label, oral tablets of sitagliptin and metformin. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning on Day 1. The dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients continued to take open-label sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the Phase A treatment period of up to 24 weeks. Results presented for the OLC are through Week 24. Patients in the OLC completed the study at Week 24.
|
|---|---|---|---|---|---|---|---|
|
54-Week Base Study
Adverse Event
|
12
|
9
|
11
|
6
|
5
|
11
|
3
|
|
54-Week Base Study
Death
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
|
54-Week Base Study
Lack of Efficacy
|
11
|
14
|
8
|
4
|
3
|
14
|
19
|
|
54-Week Base Study
Lost to Follow-up
|
5
|
4
|
7
|
5
|
10
|
9
|
3
|
|
54-Week Base Study
Physician Decision
|
1
|
1
|
0
|
0
|
1
|
0
|
0
|
|
54-Week Base Study
Pregnancy
|
1
|
0
|
0
|
0
|
1
|
0
|
1
|
|
54-Week Base Study
Protocol Violation
|
6
|
4
|
2
|
4
|
0
|
3
|
3
|
|
54-Week Base Study
Withdrawal by Subject
|
17
|
16
|
16
|
15
|
10
|
15
|
4
|
|
54-Week Base Study
protocol discontinuation criteria
|
2
|
5
|
2
|
6
|
5
|
3
|
5
|
|
54-Week Base Study
patient moved
|
0
|
1
|
1
|
2
|
3
|
1
|
0
|
|
54-Week Base Study
non-compliance with study procedures
|
1
|
2
|
0
|
0
|
0
|
2
|
0
|
|
54-Week Base Study
patient incarcerated
|
0
|
0
|
0
|
0
|
1
|
1
|
0
|
|
54-Week Base Study
laboratory reporting error
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
54-Week Base Study
site error
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
54-Week Base Study
patient intolerance to rescue therapy
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
50-Week Extension Study
Adverse Event
|
2
|
3
|
2
|
0
|
1
|
1
|
0
|
|
50-Week Extension Study
Death
|
0
|
0
|
0
|
1
|
0
|
1
|
0
|
|
50-Week Extension Study
Lack of Efficacy
|
26
|
15
|
13
|
16
|
8
|
8
|
0
|
|
50-Week Extension Study
Lost to Follow-up
|
4
|
0
|
1
|
4
|
3
|
3
|
0
|
|
50-Week Extension Study
Physician Decision
|
0
|
1
|
1
|
0
|
0
|
0
|
0
|
|
50-Week Extension Study
Pregnancy
|
0
|
0
|
1
|
0
|
1
|
0
|
0
|
|
50-Week Extension Study
Protocol Violation
|
1
|
1
|
1
|
2
|
0
|
1
|
0
|
|
50-Week Extension Study
Withdrawal by Subject
|
2
|
5
|
2
|
8
|
3
|
3
|
0
|
|
50-Week Extension Study
protocol discontinuation criteria
|
2
|
2
|
3
|
2
|
3
|
3
|
0
|
|
50-Week Extension Study
non-compliance with study procedures
|
1
|
0
|
0
|
1
|
1
|
0
|
0
|
|
50-Week Extension Study
patient moved
|
0
|
0
|
1
|
2
|
0
|
0
|
0
|
|
50-Week Extension Study
patient scheduled for elective surgery
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
50-Week Extension Study
reason unspecified
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
MK0431 (Sitagliptin) and Metformin Co-Administration Factorial Study in Patients With Type 2 Diabetes Mellitus (0431-036)
Baseline characteristics by cohort
| Measure |
Sitagliptin 100 mg q.d.
n=179 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
n=182 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
n=182 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=190 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=182 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=176 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC
n=117 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) OLC (Open-label Cohort) includes data from non-randomized patients assigned to receive treatment with open-label, oral tablets of sitagliptin and metformin. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning on Day 1. The dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients continued to take open-label sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the Phase A treatment period of up to 24 weeks. Results presented for the OLC are through Week 24. Patients in the OLC completed the study at Week 24.
|
Total
n=1208 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Race/Ethnicity, Customized
White
|
93 participants
n=5 Participants
|
87 participants
n=7 Participants
|
106 participants
n=5 Participants
|
102 participants
n=4 Participants
|
95 participants
n=21 Participants
|
81 participants
n=8 Participants
|
44 participants
n=8 Participants
|
608 participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Black
|
11 participants
n=5 Participants
|
12 participants
n=7 Participants
|
9 participants
n=5 Participants
|
13 participants
n=4 Participants
|
14 participants
n=21 Participants
|
17 participants
n=8 Participants
|
9 participants
n=8 Participants
|
85 participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
52 participants
n=5 Participants
|
55 participants
n=7 Participants
|
39 participants
n=5 Participants
|
55 participants
n=4 Participants
|
49 participants
n=21 Participants
|
47 participants
n=8 Participants
|
54 participants
n=8 Participants
|
351 participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Asian
|
6 participants
n=5 Participants
|
14 participants
n=7 Participants
|
10 participants
n=5 Participants
|
9 participants
n=4 Participants
|
11 participants
n=21 Participants
|
12 participants
n=8 Participants
|
1 participants
n=8 Participants
|
63 participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Other
|
17 participants
n=5 Participants
|
14 participants
n=7 Participants
|
18 participants
n=5 Participants
|
11 participants
n=4 Participants
|
13 participants
n=21 Participants
|
19 participants
n=8 Participants
|
9 participants
n=8 Participants
|
101 participants
n=24 Participants
|
|
HbA1c (Hemoglobin A1c)
|
8.9 Percent
STANDARD_DEVIATION 1.0 • n=5 Participants
|
8.9 Percent
STANDARD_DEVIATION 1.0 • n=7 Participants
|
8.7 Percent
STANDARD_DEVIATION 0.9 • n=5 Participants
|
8.8 Percent
STANDARD_DEVIATION 1.0 • n=4 Participants
|
8.7 Percent
STANDARD_DEVIATION 0.9 • n=21 Participants
|
8.7 Percent
STANDARD_DEVIATION 1.0 • n=8 Participants
|
11.2 Percent
STANDARD_DEVIATION 1.2 • n=8 Participants
|
9.0 Percent
STANDARD_DEVIATION 1.2 • n=24 Participants
|
|
Age, Continuous
|
53.3 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
53.4 years
STANDARD_DEVIATION 10.2 • n=7 Participants
|
53.2 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
54.1 years
STANDARD_DEVIATION 10.0 • n=4 Participants
|
53.3 years
STANDARD_DEVIATION 9.6 • n=21 Participants
|
53.6 years
STANDARD_DEVIATION 10.0 • n=8 Participants
|
52.6 years
STANDARD_DEVIATION 10.0 • n=8 Participants
|
53.4 years
STANDARD_DEVIATION 9.9 • n=24 Participants
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Sex: Female, Male
Female
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86 Participants
n=5 Participants
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93 Participants
n=7 Participants
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100 Participants
n=5 Participants
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85 Participants
n=4 Participants
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105 Participants
n=21 Participants
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83 Participants
n=8 Participants
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50 Participants
n=8 Participants
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602 Participants
n=24 Participants
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Sex: Female, Male
Male
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93 Participants
n=5 Participants
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89 Participants
n=7 Participants
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82 Participants
n=5 Participants
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105 Participants
n=4 Participants
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77 Participants
n=21 Participants
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93 Participants
n=8 Participants
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67 Participants
n=8 Participants
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606 Participants
n=24 Participants
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PRIMARY outcome
Timeframe: Week 24Population: 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 observed measurement was carried forward to Week 24. The Open-label Cohort group was excluded from the FAS.
HbA1c is measured as a percent. This change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=175 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
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Metformin 500 mg b.i.d.
n=178 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Metformin 1000 mg b.i.d.
n=177 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=183 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=178 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Placebo/Metformin 1000 mg b.i.d.
n=165 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
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|---|---|---|---|---|---|---|
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Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24
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-0.66 Percent
Interval -0.83 to -0.5
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-0.82 Percent
Interval -0.98 to -0.66
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-1.13 Percent
Interval -1.29 to -0.97
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-1.40 Percent
Interval -1.56 to -1.24
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-1.90 Percent
Interval -2.06 to -1.74
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0.17 Percent
Interval 0.0 to 0.33
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SECONDARY outcome
Timeframe: Week 24Population: 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 observed measurement was carried forward to Week 24. The Open-label Cohort group was excluded from the FAS.
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=178 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
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Metformin 500 mg b.i.d.
n=179 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Metformin 1000 mg b.i.d.
n=179 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=183 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=180 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Placebo/Metformin 1000 mg b.i.d.
n=169 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
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|---|---|---|---|---|---|---|
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Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24
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-17.5 mg/dL
Interval -24.1 to -10.8
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-27.3 mg/dL
Interval -34.0 to -20.7
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-29.3 mg/dL
Interval -35.9 to -22.6
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-47.1 mg/dL
Interval -53.7 to -40.6
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-63.9 mg/dL
Interval -70.5 to -57.3
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5.8 mg/dL
Interval -1.0 to 12.7
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SECONDARY outcome
Timeframe: Week 24Population: 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 observed measurement was carried forward to Week 24. The Open-label Cohort group was excluded from the FAS.
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=136 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
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Metformin 500 mg b.i.d.
n=141 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Metformin 1000 mg b.i.d.
n=138 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
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Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=147 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=152 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=129 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
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|---|---|---|---|---|---|---|
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Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24
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-51.9 mg/dL
Interval -62.3 to -41.5
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-53.4 mg/dL
Interval -63.6 to -43.2
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-78.0 mg/dL
Interval -88.3 to -67.6
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-92.5 mg/dL
Interval -102.6 to -82.5
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-116.6 mg/dL
Interval -126.4 to -106.7
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0.3 mg/dL
Interval -10.4 to 11.0
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SECONDARY outcome
Timeframe: Week 54Population: The Phase B Full Analysis Set (BFAS) included all patients with a baseline value and ≥1 value in Phase B (post-Week 24) for this outcome. Data following glycemic rescue were treated as missing. For BFAS patients with no data at Week 54, the last observed measurement was carried forward to Week 54.
HbA1c is measured as a percent. This change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=106 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
n=117 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
n=134 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=147 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=153 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=78 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54
|
-0.82 Percent
Interval -1.0 to -0.63
|
-1.01 Percent
Interval -1.18 to -0.83
|
-1.34 Percent
Interval -1.5 to -1.17
|
-1.41 Percent
Interval -1.57 to -1.25
|
-1.80 Percent
Interval -1.96 to -1.65
|
-1.10 Percent
Interval -1.32 to -0.88
|
SECONDARY outcome
Timeframe: Week 54Population: The Phase B Full Analysis Set (BFAS) included all patients with a baseline value and ≥1 value in Phase B (post-Week 24) for this outcome. Data following glycemic rescue were treated as missing. For BFAS patients with no data at Week 54, the last observed measurement was carried forward to Week 54.
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=105 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
n=117 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
n=134 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=146 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=153 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=78 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54
|
-16.0 mg/dL
Interval -23.2 to -8.7
|
-29.0 mg/dL
Interval -35.9 to -22.2
|
-39.6 mg/dL
Interval -46.0 to -33.2
|
-42.5 mg/dL
Interval -48.6 to -36.3
|
-55.6 mg/dL
Interval -61.6 to -49.6
|
-43.9 mg/dL
Interval -52.3 to -35.5
|
SECONDARY outcome
Timeframe: Week 54Population: The Phase B Full Analysis Set (BFAS) included all patients with a baseline value and ≥1 value in Phase B (post-Week 24) for this outcome. Data following glycemic rescue were treated as missing. For BFAS patients with no data at Week 54, the last observed measurement was carried forward to Week 54.
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=87 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
n=92 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
n=116 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=121 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=132 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=66 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54
|
-45.9 mg/dL
Interval -57.2 to -34.6
|
-58.6 mg/dL
Interval -69.6 to -47.6
|
-76.3 mg/dL
Interval -86.1 to -66.5
|
-89.6 mg/dL
Interval -99.2 to -80.0
|
-107.9 mg/dL
Interval -117.1 to -98.7
|
-80.9 mg/dL
Interval -93.9 to -67.9
|
SECONDARY outcome
Timeframe: Week 104Population: The Extension Full Analysis Set (EFAS) included all patients with a baseline value and ≥1 value in the extension (post-Week 54) for this outcome. Data following glycemic rescue were treated as missing. For EFAS patients with no data at Week 104, the last observed measurement was carried forward.
HbA1c is measured as a percent. This change from baseline reflects the Week 104 HbA1c percent minus the Week 0 HbA1c percent.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=50 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
n=64 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
n=87 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=96 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=105 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=42 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104
|
-1.15 Percent
Interval -1.37 to -0.92
|
-1.06 Percent
Interval -1.26 to -0.87
|
-1.34 Percent
Interval -1.51 to -1.17
|
-1.39 Percent
Interval -1.55 to -1.22
|
-1.66 Percent
Interval -1.81 to -1.5
|
-1.39 Percent
Interval -1.63 to -1.15
|
SECONDARY outcome
Timeframe: Week 104Population: The Extension Full Analysis Set (EFAS) included all patients with a baseline value and ≥1 value in the extension (post-Week 54) for this outcome. Data following glycemic rescue were treated as missing. For EFAS patients with no data at Week 104, the last observed measurement was carried forward.
Change from baseline at Week 104 is defined as Week 104 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=50 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
n=63 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
n=87 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=96 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=105 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=41 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104
|
-26.8 mg/dL
Interval -36.2 to -17.4
|
-41.4 mg/dL
Interval -49.8 to -33.0
|
-43.2 mg/dL
Interval -50.3 to -36.2
|
-47.5 mg/dL
Interval -54.3 to -40.7
|
-57.3 mg/dL
Interval -63.7 to -50.8
|
-45.2 mg/dL
Interval -55.7 to -34.8
|
SECONDARY outcome
Timeframe: Week 104Population: The Extension Full Analysis Set (EFAS) included all patients with a baseline value and ≥1 value in the extension (post-Week 54) for this outcome. Data following glycemic rescue were treated as missing. For EFAS patients with no data at Week 104, the last observed measurement was carried forward.
Change from baseline at Week 104 is defined as Week 104 minus Week 0.
Outcome measures
| Measure |
Sitagliptin 100 mg q.d.
n=40 Participants
The Sitagliptin 100 mg q.d. (q.d. = once daily) group includes data from patients randomized to receive treatment with two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
n=49 Participants
The Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
n=69 Participants
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
n=78 Participants
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily)and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
n=88 Participants
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily.) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
n=31 Participants
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily.) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104
|
-74.1 mg/dL
Interval -90.3 to -57.9
|
-72.7 mg/dL
Interval -87.4 to -58.1
|
-86.7 mg/dL
Interval -99.0 to -74.5
|
-96.2 mg/dL
Interval -107.8 to -84.6
|
-110.0 mg/dL
Interval -120.9 to -99.1
|
-93.3 mg/dL
Interval -111.8 to -74.9
|
Adverse Events
Sitagliptin 100 mg q.d.
Serious events: 15 serious events
Other events: 71 other events
Deaths: 0 deaths
Metformin 500 mg b.i.d.
Serious events: 10 serious events
Other events: 74 other events
Deaths: 0 deaths
Metformin 1000 mg b.i.d.
Serious events: 14 serious events
Other events: 99 other events
Deaths: 0 deaths
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
Serious events: 17 serious events
Other events: 87 other events
Deaths: 0 deaths
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
Serious events: 13 serious events
Other events: 94 other events
Deaths: 0 deaths
Placebo/Metformin 1000 mg b.i.d.
Serious events: 23 serious events
Other events: 73 other events
Deaths: 0 deaths
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC
Serious events: 3 serious events
Other events: 40 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
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 two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
The Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) OLC (Open-label Cohort) includes data from non-randomized patients assigned to receive treatment with open-label, oral tablets of sitagliptin and metformin. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning on Day 1. The dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients continued to take open-label sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the Phase A treatment period of up to 24 weeks. Results presented for the OLC are through Week 24. Patients in the OLC completed the study at Week 24.
|
|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Any Blood And Lymphatic System Disorders
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Blood and lymphatic system disorders
Lymphadenopathy Mediastinal
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Cardiac disorders
Any Cardiac Disorders
|
1.1%
2/179
|
0.55%
1/182
|
1.6%
3/182
|
1.6%
3/190
|
1.6%
3/182
|
2.3%
4/176
|
0.00%
0/117
|
|
Cardiac disorders
Acute Coronary Syndrome
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Cardiac disorders
Angina Unstable
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Cardiac disorders
Cardiac Failure
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Cardiac disorders
Coronary Artery Disease
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
1.7%
3/176
|
0.00%
0/117
|
|
Cardiac disorders
Myocardial Infarction
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
1.1%
2/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Cardiac disorders
Myocardial Ischaemia
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Cardiac disorders
Palpitations
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Congenital, familial and genetic disorders
Any Congenital, Familial And Genetic Disorders
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Congenital, familial and genetic disorders
Exomphalos
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Ear and labyrinth disorders
Any Ear And Labyrinth Disorders
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Ear and labyrinth disorders
Vertigo Positional
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Gastrointestinal disorders
Any Gastrointestinal Disorders
|
0.56%
1/179
|
0.00%
0/182
|
0.55%
1/182
|
0.53%
1/190
|
1.1%
2/182
|
1.1%
2/176
|
0.00%
0/117
|
|
Gastrointestinal disorders
Abdominal Hernia
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Gastrointestinal disorders
Pancreatitis Acute
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Gastrointestinal disorders
Swollen Tongue
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Gastrointestinal disorders
Umbilical Hernia, Obstructive
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
General disorders
Any General Disorders And Administration Site Conditions
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
1.6%
3/190
|
0.00%
0/182
|
1.7%
3/176
|
0.00%
0/117
|
|
General disorders
Death
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
General disorders
Hernia Obstructive
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
General disorders
Non-Cardiac Chest Pain
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
1.1%
2/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
General disorders
Sudden Cardiac Death
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Hepatobiliary disorders
Any Hepatobiliary Disorders
|
0.00%
0/179
|
0.55%
1/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
1.7%
3/176
|
0.00%
0/117
|
|
Hepatobiliary disorders
Cholangitis Acute
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
1.1%
2/176
|
0.00%
0/117
|
|
Immune system disorders
Any Immune System Disorders
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Immune system disorders
Anaphylactic Reaction
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Infections and infestations
Any Infections And Infestations
|
1.7%
3/179
|
1.1%
2/182
|
0.55%
1/182
|
0.53%
1/190
|
1.6%
3/182
|
2.3%
4/176
|
0.85%
1/117
|
|
Infections and infestations
Arthritis Infective
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Infections and infestations
Bronchitis
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Infections and infestations
Cellulitis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Infections and infestations
Diabetic Foot Infection
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Infections and infestations
Erysipelas
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Infections and infestations
Perineal Abscess
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Infections and infestations
Peritonsillar Abscess
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Infections and infestations
Pneumonia
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
1.1%
2/182
|
0.00%
0/176
|
0.85%
1/117
|
|
Infections and infestations
Scrotal Abscess
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Infections and infestations
Sepsis
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Any Injury, Poisoning And Procedural Complications
|
0.56%
1/179
|
0.55%
1/182
|
2.2%
4/182
|
0.53%
1/190
|
1.1%
2/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Acetabulum Fracture
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Electric Shock
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Hand Fracture
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Meniscus Lesion
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Multiple Injuries
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Postoperative Thoracic Procedure Complication
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Tendon Injury
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Tendon Rupture
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Injury, poisoning and procedural complications
Upper Limb Fracture
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Investigations
Any Investigations
|
0.00%
0/178
|
0.00%
0/181
|
0.00%
0/181
|
0.00%
0/188
|
0.55%
1/181
|
0.00%
0/172
|
0.00%
0/115
|
|
Investigations
Blood triglycerides increased
|
0.00%
0/163
|
0.00%
0/171
|
0.00%
0/170
|
0.00%
0/182
|
0.58%
1/171
|
0.00%
0/158
|
0.00%
0/107
|
|
Metabolism and nutrition disorders
Any Metabolism And Nutrition Disorders
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Metabolism and nutrition disorders
Gestational Diabetes
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Musculoskeletal and connective tissue disorders
Any Musculoskeletal And Connective Tissue Disorders
|
0.00%
0/179
|
0.55%
1/182
|
0.55%
1/182
|
0.53%
1/190
|
1.1%
2/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Any Neoplasms Benign, Malignant And Unspecified
|
2.2%
4/179
|
1.6%
3/182
|
1.1%
2/182
|
1.1%
2/190
|
0.55%
1/182
|
2.3%
4/176
|
0.85%
1/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.55%
1/182
|
0.57%
1/176
|
0.85%
1/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Neoplasm
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
0.00%
0/179
|
0.00%
0/182
|
0.55%
1/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glomus Tumour
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal Adenocarcinoma
|
0.00%
0/179
|
0.55%
1/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic Carcinoma
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pyogenic Granuloma
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Cell Carcinoma Stage Unspecified
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Retroperitoneal Neoplasm
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Nervous system disorders
Any Nervous System Disorders
|
1.1%
2/179
|
0.00%
0/182
|
0.00%
0/182
|
1.1%
2/190
|
0.00%
0/182
|
2.3%
4/176
|
0.00%
0/117
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Nervous system disorders
Cervicobrachial Syndrome
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Nervous system disorders
Syncope
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Nervous system disorders
Thalamic Infarction
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Nervous system disorders
Transient Ischaemic Attack
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.57%
1/176
|
0.00%
0/117
|
|
Renal and urinary disorders
Any Renal And Urinary Disorders
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Renal and urinary disorders
Micturition Urgency
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Reproductive system and breast disorders
Any Reproductive System And Breast Disorders
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Reproductive system and breast disorders
Adenomyosis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.55%
1/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Reproductive system and breast disorders
Endometrial Hyperplasia
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Respiratory, thoracic and mediastinal disorders
Any Respiratory, Thoracic And Mediastinal Disorders
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.53%
1/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
|
Vascular disorders
Any Vascular Disorders
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.85%
1/117
|
|
Vascular disorders
Peripheral Vascular Disorder
|
0.00%
0/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.85%
1/117
|
|
Vascular disorders
Varicose Vein
|
0.56%
1/179
|
0.00%
0/182
|
0.00%
0/182
|
0.00%
0/190
|
0.00%
0/182
|
0.00%
0/176
|
0.00%
0/117
|
Other adverse events
| Measure |
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 two 50 mg oral tablets of sitagliptin once daily for up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study). Note: In this double-blind, double-dummy study, randomized patients in the base study received a total of 7 tablets (active or placebo) per day administered in the specified tablet images as follows: sitagliptin 50 mg 2 tablets in the morning and 1 tablet in the evening, metformin 500 mg 2 tablets b.i.d. (b.i.d. = twice daily). In the extension study, patients received a total of 7 tablets (active or placebo) per day. Tablets in the image of sitagliptin (active or placebo) were administered as sitagliptin 100 mg 1 tablet in the morning and sitagliptin 50 mg 1 tablet b.i.d. Metformin administration occurred in the same manner as specified in the base study.
|
Metformin 500 mg b.i.d.
The Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 500 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased after 1 week to a stable dose of 500 mg b.i.d. Patients in this group continued to take metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Metformin 1000 mg b.i.d.
The Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of metformin 1000 mg b.i.d. Treatment was administered as 500 mg q.d. (q.d. = once daily) beginning at randomization/Day 1 and increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d.
The Sitagliptin 50 mg b.i.d. + Metformin 500 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 500 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; after 1-week, the dose of sitagliptin was increased to 50 mg b.i.d. and the dose of metformin was increased to 500 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 500 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d.
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) group includes data from patients randomized to receive treatment with oral tablets of sitagliptin 50 mg b.i.d + metformin 1000 mg b.i.d. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning at randomization/Day 1; the dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients in this group continued to take sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the treatment period of up to 104 weeks (including the 54-week base study \[24-week, placebo-controlled Phase A and 30-week, active-controlled Phase B\] and 50-week extension study).
|
Placebo/Metformin 1000 mg b.i.d.
The Placebo/Metformin 1000 mg b.i.d. group (b.i.d. = twice daily) includes data from patients randomized to receive the sequence of treatment with oral tablets of placebo (randomization/Day 1 through Week 24) followed by metformin. Beginning at Week 24, patients were switched in a blinded manner to active treatment with metformin administered as 500 mg q.d. (q.d. = once daily) increased over 4 weeks by increments of 500 mg per week to a stable dose of 1000 mg b.i.d. Patients in this group continued to take metformin 1000 mg b.i.d for the remainder of the up to 30-week Phase B base study treatment period and during the extension study of up to 50 weeks.
|
Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. OLC
The Sitagliptin 50 mg b.i.d + Metformin 1000 mg b.i.d. (b.i.d. = twice daily) OLC (Open-label Cohort) includes data from non-randomized patients assigned to receive treatment with open-label, oral tablets of sitagliptin and metformin. Treatment was co-administered as sitagliptin 50 mg q.d. (q.d. = once daily) and metformin 500 mg q.d. beginning on Day 1. The dose of sitagliptin was increased after 1-week to 50 mg b.i.d and the dose of metformin was increased over 4 weeks by increments of 500 mg per week to 1000 mg b.i.d. Patients continued to take open-label sitagliptin 50 mg b.i.d. and metformin 1000 mg b.i.d for the remainder of the Phase A treatment period of up to 24 weeks. Results presented for the OLC are through Week 24. Patients in the OLC completed the study at Week 24.
|
|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Any Gastrointestinal Disorders
|
10.6%
19/179
|
12.6%
23/182
|
23.1%
42/182
|
16.3%
31/190
|
19.2%
35/182
|
9.7%
17/176
|
15.4%
18/117
|
|
Gastrointestinal disorders
Constipation
|
5.0%
9/179
|
3.3%
6/182
|
3.3%
6/182
|
3.7%
7/190
|
1.6%
3/182
|
1.7%
3/176
|
4.3%
5/117
|
|
Gastrointestinal disorders
Diarrhoea
|
4.5%
8/179
|
7.7%
14/182
|
12.6%
23/182
|
10.0%
19/190
|
13.7%
25/182
|
6.8%
12/176
|
8.5%
10/117
|
|
Gastrointestinal disorders
Nausea
|
1.1%
2/179
|
3.3%
6/182
|
10.4%
19/182
|
5.3%
10/190
|
6.6%
12/182
|
2.3%
4/176
|
6.0%
7/117
|
|
Infections and infestations
Any Infections And Infestations
|
22.3%
40/179
|
24.2%
44/182
|
29.1%
53/182
|
28.4%
54/190
|
33.0%
60/182
|
21.0%
37/176
|
16.2%
19/117
|
|
Infections and infestations
Bronchitis
|
1.7%
3/179
|
1.6%
3/182
|
5.5%
10/182
|
3.7%
7/190
|
11.0%
20/182
|
4.5%
8/176
|
2.6%
3/117
|
|
Infections and infestations
Gastroenteritis
|
5.0%
9/179
|
0.55%
1/182
|
1.6%
3/182
|
1.6%
3/190
|
3.8%
7/182
|
1.7%
3/176
|
0.85%
1/117
|
|
Infections and infestations
Influenza
|
4.5%
8/179
|
6.0%
11/182
|
7.7%
14/182
|
5.8%
11/190
|
4.9%
9/182
|
2.8%
5/176
|
2.6%
3/117
|
|
Infections and infestations
Nasopharyngitis
|
6.1%
11/179
|
4.9%
9/182
|
6.0%
11/182
|
5.3%
10/190
|
4.9%
9/182
|
6.2%
11/176
|
5.1%
6/117
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
6.7%
12/179
|
9.3%
17/182
|
11.0%
20/182
|
11.1%
21/190
|
13.2%
24/182
|
7.4%
13/176
|
3.4%
4/117
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/179
|
4.4%
8/182
|
7.1%
13/182
|
5.8%
11/190
|
4.4%
8/182
|
2.3%
4/176
|
2.6%
3/117
|
|
Investigations
Fasting blood glucose increased
|
4.5%
8/178
|
1.7%
3/180
|
0.55%
1/181
|
0.00%
0/186
|
0.55%
1/181
|
6.4%
11/171
|
0.00%
0/115
|
|
Musculoskeletal and connective tissue disorders
Any Musculoskeletal And Connective Tissue Disorders
|
8.9%
16/179
|
11.0%
20/182
|
11.5%
21/182
|
10.0%
19/190
|
13.7%
25/182
|
7.4%
13/176
|
5.1%
6/117
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.9%
7/179
|
3.8%
7/182
|
6.0%
11/182
|
3.7%
7/190
|
7.1%
13/182
|
1.7%
3/176
|
2.6%
3/117
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
5.0%
9/179
|
4.9%
9/182
|
3.8%
7/182
|
5.8%
11/190
|
7.1%
13/182
|
5.1%
9/176
|
0.85%
1/117
|
|
Nervous system disorders
Any Nervous System Disorders
|
5.0%
9/179
|
7.1%
13/182
|
11.0%
20/182
|
8.9%
17/190
|
10.4%
19/182
|
5.7%
10/176
|
3.4%
4/117
|
|
Nervous system disorders
Dizziness
|
1.7%
3/179
|
2.7%
5/182
|
6.0%
11/182
|
1.1%
2/190
|
4.4%
8/182
|
1.7%
3/176
|
0.85%
1/117
|
|
Nervous system disorders
Headache
|
3.4%
6/179
|
4.9%
9/182
|
6.6%
12/182
|
7.9%
15/190
|
6.6%
12/182
|
4.0%
7/176
|
2.6%
3/117
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER