Trial Outcomes & Findings for A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone (NCT NCT00528879)
NCT ID: NCT00528879
Last Updated: 2015-10-20
Results Overview
HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.
COMPLETED
PHASE3
915 participants
From Baseline to Week 24
2015-10-20
Participant Flow
Of 915 participants enrolled, 562 completed a qualification period. Of these 562 participants, 546 were randomized and received treatment and 16 were excluded due to adverse events (1), no longer meeting study criteria (7), poor compliance or noncompliance (3), withdrawn consent (4), and lost to follow-up (1).
Participant milestones
| Measure |
Placebo + Metformin
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Short-term Period (Day 1 to Week 24)
STARTED
|
137
|
137
|
137
|
135
|
|
Short-term Period (Day 1 to Week 24)
Completed the Period
|
119
|
121
|
122
|
121
|
|
Short-term Period (Day 1 to Week 24)
COMPLETED
|
115
|
120
|
122
|
119
|
|
Short-term Period (Day 1 to Week 24)
NOT COMPLETED
|
22
|
17
|
15
|
16
|
|
Long-term Period (Weeks 24 to 102)
STARTED
|
115
|
120
|
122
|
119
|
|
Long-term Period (Weeks 24 to 102)
COMPLETED
|
73
|
82
|
89
|
95
|
|
Long-term Period (Weeks 24 to 102)
NOT COMPLETED
|
42
|
38
|
33
|
24
|
Reasons for withdrawal
| Measure |
Placebo + Metformin
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Short-term Period (Day 1 to Week 24)
Lack of Efficacy
|
3
|
0
|
1
|
0
|
|
Short-term Period (Day 1 to Week 24)
Adverse Event
|
4
|
4
|
2
|
4
|
|
Short-term Period (Day 1 to Week 24)
Withdrawal by Subject
|
7
|
5
|
5
|
3
|
|
Short-term Period (Day 1 to Week 24)
Lost to Follow-up
|
5
|
4
|
4
|
5
|
|
Short-term Period (Day 1 to Week 24)
Poor compliance/noncompliance
|
0
|
0
|
2
|
0
|
|
Short-term Period (Day 1 to Week 24)
No longer meets study criteria
|
2
|
3
|
0
|
2
|
|
Short-term Period (Day 1 to Week 24)
Administrative reason by author
|
1
|
1
|
0
|
1
|
|
Short-term Period (Day 1 to Week 24)
Other
|
0
|
0
|
1
|
1
|
|
Long-term Period (Weeks 24 to 102)
Lack of Efficacy
|
27
|
16
|
17
|
9
|
|
Long-term Period (Weeks 24 to 102)
Adverse Event
|
5
|
4
|
3
|
2
|
|
Long-term Period (Weeks 24 to 102)
Withdrawal by Subject
|
4
|
6
|
8
|
4
|
|
Long-term Period (Weeks 24 to 102)
Death
|
0
|
1
|
0
|
0
|
|
Long-term Period (Weeks 24 to 102)
Lost to Follow-up
|
4
|
5
|
3
|
7
|
|
Long-term Period (Weeks 24 to 102)
Poor compliance/noncompliance
|
0
|
5
|
1
|
2
|
|
Long-term Period (Weeks 24 to 102)
Pregnancy
|
1
|
0
|
0
|
0
|
|
Long-term Period (Weeks 24 to 102)
No longer meets study criteria
|
1
|
1
|
1
|
0
|
Baseline Characteristics
A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone
Baseline characteristics by cohort
| Measure |
Placebo + Metformin
n=137 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Total
n=546 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
53.7 Years
n=5 Participants
|
55.0 Years
n=7 Participants
|
54.3 Years
n=5 Participants
|
52.7 Years
n=4 Participants
|
53.9 Years
n=21 Participants
|
|
Age, Customized
Younger than 65 years
|
114 Participants
n=5 Participants
|
116 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
118 Participants
n=4 Participants
|
467 Participants
n=21 Participants
|
|
Age, Customized
65 to younger than 75 years
|
23 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
75 Participants
n=21 Participants
|
|
Age, Customized
75 years and older
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
254 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
77 Participants
n=4 Participants
|
292 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
124 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
118 Participants
n=5 Participants
|
121 Participants
n=4 Participants
|
480 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian/Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
American Indian/Alaskan Native
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Female Age
50 Years and younger
|
25 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
87 Participants
n=21 Participants
|
|
Female Age
Older than 50 years
|
36 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
167 Participants
n=21 Participants
|
|
Body Mass Index
<25 kg/m^2
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
37 Participants
n=21 Participants
|
|
Body Mass Index
≥25 kg/m^2
|
128 Participants
n=5 Participants
|
133 Participants
n=7 Participants
|
125 Participants
n=5 Participants
|
123 Participants
n=4 Participants
|
509 Participants
n=21 Participants
|
|
Body Mass Index
≥27 kg/m^2
|
115 Participants
n=5 Participants
|
120 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
106 Participants
n=4 Participants
|
452 Participants
n=21 Participants
|
|
Body Mass Index
≥30 kg/m^2
|
79 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
75 Participants
n=4 Participants
|
312 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF)
HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.
Outcome measures
| Measure |
Placebo + Metformin
n=134 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=133 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=132 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])
|
-0.30 Percent
Standard Error 0.0718
|
-0.67 Percent
Standard Error 0.0715
|
-0.70 Percent
Standard Error 0.0722
|
-0.84 Percent
Standard Error 0.0724
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication and who had nonmissing fasting plasma glucose values at baseline and Week 24 (LOCF)
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured as milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Outcome measures
| Measure |
Placebo + Metformin
n=136 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=136 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=132 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF])
|
-6.0 mg/dL
Standard Error 2.673
|
-17.8 mg/dL
Standard Error 2.663
|
-21.5 mg/dL
Standard Error 2.679
|
-23.5 mg/dL
Standard Error 2.721
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication and had nonmissing total body weights at baseline and Week 24 (LOCF)
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.
Outcome measures
| Measure |
Placebo + Metformin
n=136 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=133 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF])
|
-0.89 Kilograms
Standard Error 0.2368
|
-2.21 Kilograms
Standard Error 0.2357
|
-3.04 Kilograms
Standard Error 0.2358
|
-2.86 Kilograms
Standard Error 0.2392
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication and were not missing baseline and Week 24 (LOCF) values
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c \<7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Outcome measures
| Measure |
Placebo + Metformin
n=134 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=133 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=132 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
|
25.9 Percentage of participants
|
33.0 Percentage of participants
|
37.5 Percentage of participants
|
40.6 Percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication, who had baseline HbA1c ≥9.0%, and who had nonmissing HbA1c values at Week 24 (LOCF)
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized participants who received treatment and had a baseline HbA1c \> 9.0%. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Outcome measures
| Measure |
Placebo + Metformin
n=22 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=17 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=34 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=18 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF])
|
-0.53 Percent
Standard Error 0.2345
|
-1.21 Percent
Standard Error 0.2660
|
-1.37 Percent
Standard Error 0.1875
|
-1.32 Percent
Standard Error 0.2595
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication, who had baseline BMI ≥27 kg/m\^2, and who had nonmissing total body weight measurements at Week 24 (LOCF)
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined.) Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.
Outcome measures
| Measure |
Placebo + Metformin
n=114 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=120 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=111 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=108 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Mean Change From Baseline in Total Body Weight at Week 24 in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])
|
-1.01 Kilograms
Standard Error 0.2630
|
-2.39 Kilograms
Standard Error 0.2564
|
-3.21 Kilograms
Standard Error 0.2661
|
-3.09 Kilograms
Standard Error 0.2737
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication, who had a BMI ≥27 kg/m\^2 at baseline, and who had nonmissing HbA1c values at Week 24 (LOCF)
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted for baseline HbA1c. HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Outcome measures
| Measure |
Placebo + Metformin
n=113 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=118 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=109 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=104 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])
|
-0.31 Percent
Standard Error 0.0792
|
-0.69 Percent
Standard Error 0.0774
|
-0.71 Percent
Standard Error 0.0806
|
-0.88 Percent
Standard Error 0.0826
|
SECONDARY outcome
Timeframe: From Baseline to Week 1Population: All randomized participants who received study medication and who had nonmissing fasting plasma glucose values at baseline and Week 1 (LOCF)
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Outcome measures
| Measure |
Placebo + Metformin
n=126 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=120 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=121 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=115 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF])
|
1.2 mg/dL
Standard Error 1.934
|
-6.0 mg/dL
Standard Error 1.981
|
-12.0 mg/dL
Standard Error 1.976
|
-16.5 mg/dL
Standard Error 2.030
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication and who had HbA1c values at Baseline and Week 24 (LOCF)
Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Outcome measures
| Measure |
Placebo + Metformin
n=18 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=29 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=18 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=36 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF])
|
13.8 Percentage of participants
|
20.7 Percentage of participants
|
14.5 Percentage of participants
|
25.2 Percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From Baseline to end of Long-term Period (Week 102)Population: All randomized participants who received at least 1 dose of blinded study medication
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug. Events captured from baseline to last dose plus 4 days for AEs and plus 30 days for SAEs during the double-blind 12-week period. Data after rescue included.
Outcome measures
| Measure |
Placebo + Metformin
n=137 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
At least 1 AE
|
111 Participants
|
111 Participants
|
111 Participants
|
111 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
At least 1 hypoglycemia event
|
8 Participants
|
5 Participants
|
7 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
At least 1 related AE
|
28 Participants
|
36 Participants
|
33 Participants
|
45 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
Deaths
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
At least 1 SAE
|
14 Participants
|
15 Participants
|
9 Participants
|
14 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
At least 1 related SAE
|
3 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
SAEs leading to discontinuation
|
6 Participants
|
3 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
AEs leading to discontinuation
|
9 Participants
|
7 Participants
|
5 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
Hypoglycemia events leading to discontinuation
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Week 102Population: All randomized participants who received at least 1 dose of study medication and who had nonmissing laboratory values at baseline and Week 102.
BUN=blood urea nitrogen; preRX=pretreatment; ULN=upper limit of normal; AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Phosphorus, inorganic (low): ages 17-65 years, ≤1.8 mg/dL; ages≥66 years, ≤2.1 mg/dL. Phosphorus, inorganic (high): ages 17-65 years, ≥5.6 mg/dL; ages≥66 years, ≥5.6 mg/dL. Phosphorus, inorganic (low) ≤1.8 mg/dL if age 17-65 or ≤2.1 mg/dL if age ≥66. Calcium, total (high): ≥1 mg/dL from ULN and ≥0.5 mg/dL from preRx value.
Outcome measures
| Measure |
Placebo + Metformin
n=136 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=136 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=132 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Phosphorus, inorganic (high)
|
1 Participants
|
1 Participants
|
2 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Phosphorus, inorganic (low)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Albumin/creatinine ratio >1800 mg/g
|
2 Participants
|
0 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
AST elevation 3*ULN
|
0 Participants
|
0 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Hematocrit >55%
|
1 Participants
|
2 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Hemoglobin >18 g/dL
|
1 Participants
|
4 Participants
|
1 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
BUN ≥60 mg/d or Urea>21.4 mmol/L
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Creatinine ≥1.5 preRX creatinine
|
2 Participants
|
3 Participants
|
4 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Creatinine ≥2.5 mg/dL
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Glucose >350 mg/dL
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Creatine kinase >5*ULN
|
2 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Creatine kinase >10*ULN
|
1 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Calcium, total <7.5 mg/dL
|
4 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Calcium, total (high)
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Potassium, serum ≥6 MEQ/L
|
6 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Magnesium, serum <1 mEq/L
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Sodium, serum <130 mEq/L
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Sodium, serum >150 mEq/L
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
ALT elevation 3*ULN
|
1 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
ALT elevation 5*ULN
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Total bilirubin elevation >1.5*ULN
|
2 Participants
|
1 Participants
|
1 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
Total bilirubin elevation >2*ULN
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
ALP elevation >1.5*ULN
|
5 Participants
|
5 Participants
|
0 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 102Population: All randomized participants who received at least 1 dose of study medication and who had nonmissing baseline and Week 102 (LOCF) values
12-Lead electrocardiograms (ECGs) were performed at entry into lead-in period Day -7 visit and Week 24/dnd of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter. Data after rescue included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available.
Outcome measures
| Measure |
Placebo + Metformin
n=137 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline normal/Week 102 normal
|
74 Participants
|
80 Participants
|
79 Participants
|
82 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline normal/Week 102 abnormal
|
7 Participants
|
14 Participants
|
9 Participants
|
8 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline normal/Week 102 not reported
|
9 Participants
|
6 Participants
|
5 Participants
|
9 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline abnormal/Week 102 normal
|
17 Participants
|
11 Participants
|
20 Participants
|
10 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline abnormal/Week 102 abnormal
|
26 Participants
|
24 Participants
|
20 Participants
|
25 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline abnormal/Week 102 not reported
|
3 Participants
|
2 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline not reported/Week 102 normal
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline not reportedl/Week 102 abnormal
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
Baseline not reported/Week 102 not reported
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From Baseline to Week 102Population: All randomized participants who received study medication. n=the number of participants not missing baseline and Week t values.
Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Outcome measures
| Measure |
Placebo + Metformin
n=137 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Mean Changes From Baseline in Seated Systolic Blood Pressure
Week 12 (n=125, 129, 129, 126)
|
-0.1 mm Hg
Standard Error 1.216
|
-1.6 mm Hg
Standard Error 1.380
|
-4.0 mm Hg
Standard Error 1.206
|
-3.0 mm Hg
Standard Error 1.230
|
|
Mean Changes From Baseline in Seated Systolic Blood Pressure
Week 24 (n=119, 119, 122, 122)
|
-0.2 mm Hg
Standard Error 1.229
|
-2.1 mm Hg
Standard Error 1.126
|
-4.3 mm Hg
Standard Error 1.270
|
-5.1 mm Hg
Standard Error 1.329
|
|
Mean Changes From Baseline in Seated Systolic Blood Pressure
Week 50 (n=105, 116, 111, 113)
|
1.0 mm Hg
Standard Error 1.440
|
-0.1 mm Hg
Standard Error 1.281
|
-2.1 mm Hg
Standard Error 1.314
|
-1.9 mm Hg
Standard Error 1.472
|
|
Mean Changes From Baseline in Seated Systolic Blood Pressure
Week 102 (n=72, 78, 88, 94)
|
1.5 mm Hg
Standard Error 1.610
|
0.7 mm Hg
Standard Error 1.825
|
-1.1 mm Hg
Standard Error 1.412
|
-0.3 mm Hg
Standard Error 1.544
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From Baseline to Week 102Population: All randomized participants who received study medication. n=the number of participants not missing baseline and Week t values.
Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication.
Outcome measures
| Measure |
Placebo + Metformin
n=137 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Mean Changes From Baseline in Seated Diastolic Blood Pressure
Week 12 (n=125, 129, 129, 126)
|
-0.9 mm Hg
Standard Error 0.763
|
-1.3 mm Hg
Standard Error 0.794
|
-2.3 mm Hg
Standard Error 0.714
|
-1.0 mm Hg
Standard Error 0.758
|
|
Mean Changes From Baseline in Seated Diastolic Blood Pressure
Week 24 (n=119, 119, 122, 122)
|
-0.1 mm Hg
Standard Error 0.744
|
-1.8 mm Hg
Standard Error 0.863
|
-2.5 mm Hg
Standard Error 0.769
|
-1.8 mm Hg
Standard Error 0.842
|
|
Mean Changes From Baseline in Seated Diastolic Blood Pressure
Week 50 (n=105, 116, 111, 113)
|
0.1 mm Hg
Standard Error 0.861
|
-0.2 mm Hg
Standard Error 0.714
|
-2.4 mm Hg
Standard Error 0.840
|
-1.2 mm Hg
Standard Error 0.921
|
|
Mean Changes From Baseline in Seated Diastolic Blood Pressure
Week 102 (n=72, 78, 88, 94)
|
-1.0 mm Hg
Standard Error 0.929
|
-0.1 mm Hg
Standard Error 0.914
|
-1.5 mm Hg
Standard Error 0.861
|
-1.2 mm Hg
Standard Error 1.041
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From Baseline to Week 102Population: All randomized participants who received treatment; n=the number of participants who were not missing blood pressure measurements.
Orthostatic hypotension was defined as a decrease from supine to standing blood pressure of \>20 mm Hg in systolic blood pressure or \>10 mm Hg in diastolic blood pressure.
Outcome measures
| Measure |
Placebo + Metformin
n=137 Participants
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5 mg + Metformin
n=137 Participants
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 Participants
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Number of Participants With Orthostatic Hypotension
Week 24 (n=116, 114, 118, 121)
|
10 Participants
|
6 Participants
|
5 Participants
|
3 Participants
|
|
Number of Participants With Orthostatic Hypotension
Baseline (n=121, 127, 124, 126)
|
3 Participants
|
4 Participants
|
4 Participants
|
4 Participants
|
|
Number of Participants With Orthostatic Hypotension
Week 1 (n=126, 121, 119, 114)
|
28 Participants
|
26 Participants
|
21 Participants
|
19 Participants
|
|
Number of Participants With Orthostatic Hypotension
Week 12 (n=123, 128, 127, 125)
|
6 Participants
|
8 Participants
|
4 Participants
|
5 Participants
|
|
Number of Participants With Orthostatic Hypotension
Week 50 (n=103, 115, 109,112)
|
10 Participants
|
6 Participants
|
7 Participants
|
6 Participants
|
|
Number of Participants With Orthostatic Hypotension
Week 102 (n=71, 76, 87, 94)
|
1 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
Adverse Events
Placebo + Metformin
Dapagliflozin, 2.5 mg + Metformin
Dapagliflozin, 5.0 mg + Metformin
Dapagliflozin, 10 mg + Metformin
Serious adverse events
| Measure |
Placebo + Metformin
n=137 participants at risk
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 participants at risk
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5.0 mg + Metformin
n=137 participants at risk
Participants received dapagliflozin, 5.0 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 participants at risk
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Nervous system disorders
Cervical cord compression
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Infections and infestations
Dengue fever
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Injury, poisoning and procedural complications
Face injury
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/137
|
0.73%
1/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
General disorders
Necrobiosis
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Injury, poisoning and procedural complications
Spinal cord injury cervical
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Nervous system disorders
Transient ischaemic attack
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Cardiac disorders
Angina pectoris
|
0.73%
1/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Injury, poisoning and procedural complications
Fall
|
0.73%
1/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphocytic leukaemia
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/137
|
1.5%
2/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Cardiac disorders
Angina unstable
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Injury, poisoning and procedural complications
Urethral injury
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Infections and infestations
Appendicitis
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Cardiac disorders
Coronary artery stenosis
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Gastrointestinal disorders
Inguinal hernia, obstructive
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Cardiac disorders
Myocardial ischaemia
|
0.73%
1/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Injury, poisoning and procedural complications
Open fracture
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectosigmoid cancer
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.74%
1/135
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Cardiac disorders
Cardiac arrest
|
1.5%
2/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Gastrointestinal disorders
Diabetic gastroparesis
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Nervous system disorders
Ischaemic stroke
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/137
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/135
|
|
Nervous system disorders
Syncope
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Cardiac disorders
Acute myocardial infarction
|
2.2%
3/137
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Cardiac disorders
Atrioventricular block second degree
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
Reproductive system and breast disorders
Breast mass
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
0.74%
1/135
|
|
General disorders
Chest pain
|
0.00%
0/137
|
0.00%
0/137
|
0.00%
0/137
|
1.5%
2/135
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/137
|
0.73%
1/137
|
0.00%
0/137
|
0.00%
0/135
|
Other adverse events
| Measure |
Placebo + Metformin
n=137 participants at risk
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 2.5 mg + Metformin
n=137 participants at risk
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 5.0 mg + Metformin
n=137 participants at risk
Participants received dapagliflozin, 5.0 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
Dapagliflozin, 10 mg + Metformin
n=135 participants at risk
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
5.8%
8/137
|
7.3%
10/137
|
9.5%
13/137
|
11.1%
15/135
|
|
Vascular disorders
Hypertension
|
9.5%
13/137
|
8.0%
11/137
|
5.8%
8/137
|
5.2%
7/135
|
|
Infections and infestations
Influenza
|
10.9%
15/137
|
13.9%
19/137
|
14.6%
20/137
|
12.6%
17/135
|
|
Gastrointestinal disorders
Vomiting
|
1.5%
2/137
|
4.4%
6/137
|
5.1%
7/137
|
3.0%
4/135
|
|
Infections and infestations
Bronchitis
|
2.9%
4/137
|
4.4%
6/137
|
3.6%
5/137
|
7.4%
10/135
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.8%
12/137
|
3.6%
5/137
|
3.6%
5/137
|
4.4%
6/135
|
|
Gastrointestinal disorders
Diarrhoea
|
7.3%
10/137
|
5.1%
7/137
|
6.6%
9/137
|
11.9%
16/135
|
|
Nervous system disorders
Dizziness
|
5.1%
7/137
|
3.6%
5/137
|
4.4%
6/137
|
0.74%
1/135
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.0%
11/137
|
8.0%
11/137
|
5.1%
7/137
|
13.3%
18/135
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
3.6%
5/137
|
3.6%
5/137
|
3.6%
5/137
|
5.2%
7/135
|
|
Infections and infestations
Gastroenteritis
|
5.1%
7/137
|
3.6%
5/137
|
5.1%
7/137
|
3.0%
4/135
|
|
Infections and infestations
Nasopharyngitis
|
8.8%
12/137
|
11.7%
16/137
|
5.8%
8/137
|
8.9%
12/135
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.0%
11/137
|
5.8%
8/137
|
2.2%
3/137
|
1.5%
2/135
|
|
Infections and infestations
Upper respiratory tract infection
|
10.2%
14/137
|
6.6%
9/137
|
3.6%
5/137
|
3.7%
5/135
|
|
Infections and infestations
Urinary tract infection
|
5.8%
8/137
|
3.6%
5/137
|
5.8%
8/137
|
11.9%
16/135
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.1%
7/137
|
5.8%
8/137
|
7.3%
10/137
|
3.0%
4/135
|
|
Infections and infestations
Pharyngitis
|
2.2%
3/137
|
5.1%
7/137
|
3.6%
5/137
|
5.9%
8/135
|
|
Psychiatric disorders
Depression
|
1.5%
2/137
|
5.8%
8/137
|
0.73%
1/137
|
2.2%
3/135
|
|
Gastrointestinal disorders
Nausea
|
2.9%
4/137
|
4.4%
6/137
|
2.9%
4/137
|
5.2%
7/135
|
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