Trial Outcomes & Findings for A Phase 3 Study of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise (NCT NCT00327015)
NCT ID: NCT00327015
Last Updated: 2015-04-29
Results Overview
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1306 participants
Primary outcome timeframe
Baseline, Week 24
Results posted on
2015-04-29
Participant Flow
Participant milestones
| Measure |
Saxagliptin 5 mg + Metformin
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin Immediate Release (IR) was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
Metformin
The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
320
|
323
|
335
|
328
|
|
Overall Study
Completed Study Without Being Rescued
|
179
|
177
|
113
|
144
|
|
Overall Study
COMPLETED
|
229
|
231
|
209
|
219
|
|
Overall Study
NOT COMPLETED
|
91
|
92
|
126
|
109
|
Reasons for withdrawal
| Measure |
Saxagliptin 5 mg + Metformin
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin Immediate Release (IR) was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
Metformin
The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.
|
|---|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
18
|
18
|
35
|
29
|
|
Overall Study
Withdrawal of Consent by Subject
|
20
|
24
|
28
|
25
|
|
Overall Study
Lost to Follow-up
|
22
|
23
|
29
|
22
|
|
Overall Study
Adverse Event
|
14
|
10
|
14
|
14
|
|
Overall Study
Subject no longer meets study criteria
|
4
|
2
|
8
|
7
|
|
Overall Study
Poor/Noncompliance
|
11
|
8
|
4
|
5
|
|
Overall Study
Physician Decision
|
0
|
1
|
3
|
2
|
|
Overall Study
Death
|
1
|
2
|
2
|
3
|
|
Overall Study
Pregnancy
|
0
|
2
|
1
|
1
|
|
Overall Study
Administrative Reason by Sponsor
|
1
|
2
|
2
|
1
|
Baseline Characteristics
A Phase 3 Study of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise
Baseline characteristics by cohort
| Measure |
Saxagliptin 5 mg + Metformin
n=320 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin Immediate Release (IR) was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=323 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=335 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
Metformin
n=328 Participants
The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.
|
Total
n=1306 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
51.95 years
STANDARD_DEVIATION 10.43 • n=5 Participants
|
52.08 years
STANDARD_DEVIATION 11.59 • n=7 Participants
|
52.09 years
STANDARD_DEVIATION 10.17 • n=5 Participants
|
51.83 years
STANDARD_DEVIATION 10.74 • n=4 Participants
|
51.99 years
STANDARD_DEVIATION 10.73 • n=21 Participants
|
|
Sex: Female, Male
Female
|
155 Participants
n=5 Participants
|
177 Participants
n=7 Participants
|
166 Participants
n=5 Participants
|
165 Participants
n=4 Participants
|
663 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
165 Participants
n=5 Participants
|
146 Participants
n=7 Participants
|
169 Participants
n=5 Participants
|
163 Participants
n=4 Participants
|
643 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 Last Observation Carried Forward (LOCF), subjects must have had a baseline and at least 1 post-baseline measurement. If participant received rescue medication, that measurement must have been taken before rescue.
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=306 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=315 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=317 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Baseline Mean
|
9.41 percent
Standard Error 0.072
|
9.53 percent
Standard Error 0.069
|
9.61 percent
Standard Error 0.075
|
|
Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Week 24 Mean
|
6.93 percent
Standard Error 0.066
|
7.02 percent
Standard Error 0.067
|
7.86 percent
Standard Error 0.085
|
|
Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Adjusted Mean Change from Baseline
|
-2.53 percent
Standard Error 0.070
|
-2.49 percent
Standard Error 0.069
|
-1.69 percent
Standard Error 0.069
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=306 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=315 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=313 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Baseline Mean
|
9.41 percent
Standard Error 0.072
|
9.53 percent
Standard Error 0.069
|
9.43 percent
Standard Error 0.073
|
|
Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Week 24 Mean
|
6.93 percent
Standard Error 0.066
|
7.02 percent
Standard Error 0.067
|
7.48 percent
Standard Error 0.084
|
|
Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Adjusted Mean Change from Baseline
|
-2.53 percent
Standard Error 0.070
|
-2.49 percent
Standard Error 0.069
|
-1.99 percent
Standard Error 0.069
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=315 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=317 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=327 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Baseline Mean
|
198.9 mg/dL
Standard Error 3.17
|
204.3 mg/dL
Standard Error 3.35
|
200.9 mg/dL
Standard Error 3.03
|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Week 24 Mean
|
140.2 mg/dL
Standard Error 2.39
|
140.1 mg/dL
Standard Error 2.34
|
169.9 mg/dL
Standard Error 3.20
|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Adjusted Mean Change from Baseline
|
-59.8 mg/dL
Standard Error 2.34
|
-62.2 mg/dL
Standard Error 2.34
|
-30.9 mg/dL
Standard Error 2.30
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=315 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=317 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=320 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Baseline Mean
|
198.9 mg/dL
Standard Error 3.17
|
204.3 mg/dL
Standard Error 3.35
|
199.1 mg/dL
Standard Error 3.28
|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Week 24 Mean
|
140.2 mg/dL
Standard Error 2.39
|
140.1 mg/dL
Standard Error 2.34
|
152.7 mg/dL
Standard Error 2.80
|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Adjusted Mean Change from Baseline
|
-59.8 mg/dL
Standard Error 2.34
|
-62.2 mg/dL
Standard Error 2.34
|
-47.3 mg/dL
Standard Error 2.33
|
SECONDARY outcome
Timeframe: Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Percentage of participants achieving A1C \< 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=307 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=315 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=320 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
|
60.3 Percentage of participants
|
59.7 Percentage of participants
|
32.2 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Percentage of participants achieving A1C \< 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus metformin alone at Week 24.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=307 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=315 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=314 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
|
60.3 Percentage of participants
|
59.7 Percentage of participants
|
41.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline value.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=142 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=131 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=145 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Baseline Mean
|
55531 mg*min/dL
Standard Error 1116.5
|
57219 mg*min/dL
Standard Error 1169.6
|
57584 mg*min/dL
Standard Error 1143.4
|
|
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Week 24 Mean
|
35324 mg*min/dL
Standard Error 890.0
|
35790 mg*min/dL
Standard Error 888.9
|
41229 mg*min/dL
Standard Error 1050.9
|
|
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
Adjusted Mean Change from Baseline
|
-21080 mg*min/dL
Standard Error 836.5
|
-21336 mg*min/dL
Standard Error 869.6
|
-16054 mg*min/dL
Standard Error 826.7
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjsuted for baseline value.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=142 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=131 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=135 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Baseline Mean
|
55531 mg*min/dL
Standard Error 1116.5
|
57219 mg*min/dL
Standard Error 1169.6
|
57937 mg*min/dL
Standard Error 1281.7
|
|
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Week 24 Mean
|
35324 mg*min/dL
Standard Error 890.0
|
35790 mg*min/dL
Standard Error 888.9
|
42428 mg*min/dL
Standard Error 1082.1
|
|
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
Adjusted Mean Change from Baseline
|
-21080 mg*min/dL
Standard Error 836.5
|
-21336 mg*min/dL
Standard Error 869.6
|
-15005 mg*min/dL
Standard Error 857.0
|
SECONDARY outcome
Timeframe: Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=307 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=315 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=320 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
|
45.3 Percentage of Participants
|
40.6 Percentage of Participants
|
20.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.
Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus metformin alone at Week 24.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=307 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=315 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=314 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
|
45.3 Percentage of participants
|
40.6 Percentage of participants
|
29.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment were included in the Week 24 LOCF analysis.
Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus saxagliptin alone.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=320 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=323 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=335 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
|
7.5 Percentage of participants
|
5.9 Percentage of participants
|
21.2 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: Randomized participants who took at least 1 dose of double-blind treatment were included in the Week 24 LOCF analysis.
Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus metformin alone.
Outcome measures
| Measure |
Saxagliptin 5 mg + Metformin
n=320 Participants
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg + Metformin
n=323 Participants
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 10 mg
n=328 Participants
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
|---|---|---|---|
|
Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
|
7.5 Percentage of participants
|
5.9 Percentage of participants
|
10.1 Percentage of participants
|
Adverse Events
Metformin
Serious events: 15 serious events
Other events: 106 other events
Deaths: 0 deaths
Saxagliptin 10 mg
Serious events: 16 serious events
Other events: 106 other events
Deaths: 0 deaths
Saxagliptin 10 mg + Metformin
Serious events: 22 serious events
Other events: 122 other events
Deaths: 0 deaths
Saxagliptin 5 mg + Metformin
Serious events: 16 serious events
Other events: 116 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Metformin
n=328 participants at risk
The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.
|
Saxagliptin 10 mg
n=335 participants at risk
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
Saxagliptin 10 mg + Metformin
n=323 participants at risk
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 5 mg + Metformin
n=320 participants at risk
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
|---|---|---|---|---|
|
Eye disorders
DIABETIC RETINOPATHY
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Cardiac disorders
CARDIAC ARREST
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.61%
2/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.61%
2/328
|
0.00%
0/335
|
0.31%
1/323
|
0.31%
1/320
|
|
Cardiac disorders
CARDIAC FAILURE ACUTE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.00%
0/328
|
0.00%
0/335
|
0.62%
2/323
|
0.00%
0/320
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.61%
2/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Cardiac disorders
ARTERIOSCLEROSIS CORONARY ARTERY
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Cardiac disorders
ATRIOVENTRICULAR BLOCK SECOND DEGREE
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Vascular disorders
EXTREMITY NECROSIS
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Vascular disorders
DIABETIC MACROANGIOPATHY
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.30%
1/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Nervous system disorders
SCIATICA
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Nervous system disorders
ISCHAEMIC STROKE
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Nervous system disorders
SYNCOPE VASOVAGAL
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Nervous system disorders
CEREBRAL INFARCTION
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Nervous system disorders
HAEMORRHAGIC STROKE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Nervous system disorders
FACIAL NERVE DISORDER
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Gastrointestinal disorders
GASTRITIS
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.31%
1/320
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Gastrointestinal disorders
HIATUS HERNIA
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Gastrointestinal disorders
FOOD POISONING
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Gastrointestinal disorders
GASTRIC POLYPS
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Gastrointestinal disorders
UMBILICAL HERNIA
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Gastrointestinal disorders
GASTRITIS EROSIVE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Gastrointestinal disorders
PANCREATITIS ACUTE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Ear and labyrinth disorders
DEAFNESS
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Infections and infestations
SEPSIS
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Infections and infestations
TETANUS
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Infections and infestations
ERYSIPELAS
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Infections and infestations
APPENDICITIS
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Infections and infestations
SCROTAL ABSCESS
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Infections and infestations
PHARYNGOTONSILLITIS
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.30%
1/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Blood and lymphatic system disorders
LYMPHOPENIA
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Blood and lymphatic system disorders
LYMPHADENITIS
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Skin and subcutaneous tissue disorders
ROSACEA
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Skin and subcutaneous tissue disorders
INGROWING NAIL
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Skin and subcutaneous tissue disorders
DERMATITIS ALLERGIC
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Reproductive system and breast disorders
MENOMETRORRHAGIA
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Reproductive system and breast disorders
ACQUIRED PHIMOSIS
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Reproductive system and breast disorders
UTERINE HAEMORRHAGE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Injury, poisoning and procedural complications
ACCIDENT
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Injury, poisoning and procedural complications
OVERDOSE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.31%
1/320
|
|
Injury, poisoning and procedural complications
WRIST FRACTURE
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Musculoskeletal and connective tissue disorders
OSTEOCHONDROSIS
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Respiratory, thoracic and mediastinal disorders
LUNG CONSOLIDATION
|
0.00%
0/328
|
0.30%
1/335
|
0.00%
0/323
|
0.00%
0/320
|
|
General disorders
PYREXIA
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
General disorders
SUDDEN DEATH
|
0.30%
1/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PAPILLOMA
|
0.00%
0/328
|
0.00%
0/335
|
0.31%
1/323
|
0.00%
0/320
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BILE DUCT CANCER
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PANCREATIC NEOPLASM
|
0.30%
1/328
|
0.00%
0/335
|
0.00%
0/323
|
0.00%
0/320
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LYMPHOPROLIFERATIVE DISORDER
|
0.00%
0/328
|
0.00%
0/335
|
0.00%
0/323
|
0.31%
1/320
|
Other adverse events
| Measure |
Metformin
n=328 participants at risk
The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.
|
Saxagliptin 10 mg
n=335 participants at risk
The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
|
Saxagliptin 10 mg + Metformin
n=323 participants at risk
The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
Saxagliptin 5 mg + Metformin
n=320 participants at risk
The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
|
|---|---|---|---|---|
|
Vascular disorders
HYPERTENSION
|
5.2%
17/328
|
5.7%
19/335
|
6.5%
21/323
|
8.4%
27/320
|
|
Nervous system disorders
HEADACHE
|
5.5%
18/328
|
9.3%
31/335
|
11.1%
36/323
|
9.7%
31/320
|
|
Gastrointestinal disorders
DIARRHOEA
|
9.1%
30/328
|
3.6%
12/335
|
12.7%
41/323
|
8.1%
26/320
|
|
Infections and infestations
INFLUENZA
|
5.8%
19/328
|
5.1%
17/335
|
4.0%
13/323
|
6.2%
20/320
|
|
Infections and infestations
NASOPHARYNGITIS
|
5.8%
19/328
|
7.2%
24/335
|
5.9%
19/323
|
9.1%
29/320
|
|
Infections and infestations
URINARY TRACT INFECTION
|
7.6%
25/328
|
6.9%
23/335
|
6.8%
22/323
|
4.1%
13/320
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
3.0%
10/328
|
4.2%
14/335
|
5.9%
19/323
|
4.7%
15/320
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER