Type 2 Diabetes
Conditions
Keywords
Diabetes Mellitus, Type 2, Diabetes Mellitus, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Diseases, Metformin, Hypoglycemic Agents, Pharmacologic Actions, Physiological Effects of Drugs
Brief summary
The purpose of this clinical research study is to learn whether dapagliflozin can help reduce blood sugar levels in participants with Type 2 diabetes that is not well controlled on metformin alone. The safety of this treatment will also be studied.
Interventions
DRUGDapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
DRUGPlacebo
Dapagliflozin-matching placebo administered as tablets orally once daily for up to 102 weeks
DRUGMetformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 77 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Males and females, 18 to 77 years old, with type 2 diabetes and inadequate glycemic control * Participants who have been receiving metformin at a total daily dose ≥1500 mg per day for at least 8 weeks * C-peptide ≥1.0 ng/mL * Body mass index ≤45.0 kg/m\^2 * Serum creatinine level \<1.50 mg/dL for men or \<1.40 mg/dL for women. Key
Exclusion criteria
* Aspartate aminotransferase and/or alanine aminotransferase level \>3.0 times the upper limit of normal * Serum total bilirubin level \>2 mg/dL * Creatinine kinase level \>3 times upper limit of normal * Symptoms of severely uncontrolled diabetes * Serum creatinine level ≥1.50 mg/dL for men or ≥1.40 mg/dL for women * Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, endocrine, psychiatric, or rheumatic diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 24 | 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. |
| Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 24 | 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. |
| Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 24 | 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. |
| 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]) | From Baseline to Week 24 | 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. |
| 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]) | From Baseline to Week 24 | 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. |
| Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 1 | 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. |
| Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 24 | 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. |
| Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF]) | From Baseline to Week 24 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline to Week 102 | 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. |
| Mean Changes From Baseline in Seated Systolic Blood Pressure | From Baseline to Week 102 | 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. |
| Mean Changes From Baseline in Seated Diastolic Blood Pressure | From Baseline to Week 102 | 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. |
| Number of Participants With Orthostatic Hypotension | From Baseline to Week 102 | 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. |
| Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Day 1 to 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. |
| 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 | From Baseline to end of Long-term Period (Week 102) | 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. |
Countries
Argentina, Brazil, Canada, Mexico, United States
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Metformin Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks | 137 |
| 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 | 137 |
| Dapagliflozin, 5 mg + Metformin Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks | 137 |
| Dapagliflozin, 10 mg + Metformin Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks | 135 |
| Total | 546 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Long-term Period (Weeks 24 to 102) | Adverse Event | 5 | 4 | 3 | 2 |
| Long-term Period (Weeks 24 to 102) | Death | 0 | 1 | 0 | 0 |
| Long-term Period (Weeks 24 to 102) | Lack of Efficacy | 27 | 16 | 17 | 9 |
| Long-term Period (Weeks 24 to 102) | Lost to Follow-up | 4 | 5 | 3 | 7 |
| Long-term Period (Weeks 24 to 102) | No longer meets study criteria | 1 | 1 | 1 | 0 |
| 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) | Withdrawal by Subject | 4 | 6 | 8 | 4 |
| Short-term Period (Day 1 to Week 24) | Administrative reason by author | 1 | 1 | 0 | 1 |
| Short-term Period (Day 1 to Week 24) | Adverse Event | 4 | 4 | 2 | 4 |
| Short-term Period (Day 1 to Week 24) | Lack of Efficacy | 3 | 0 | 1 | 0 |
| Short-term Period (Day 1 to Week 24) | Lost to Follow-up | 5 | 4 | 4 | 5 |
| 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) | Other | 0 | 0 | 1 | 1 |
| Short-term Period (Day 1 to Week 24) | Poor compliance/noncompliance | 0 | 0 | 2 | 0 |
| Short-term Period (Day 1 to Week 24) | Withdrawal by Subject | 7 | 5 | 5 | 3 |
Baseline characteristics
| Characteristic | Dapagliflozin, 2.5 mg + Metformin | Dapagliflozin, 5 mg + Metformin | Dapagliflozin, 10 mg + Metformin | Total | Placebo + Metformin |
|---|---|---|---|---|---|
| Age, Continuous | 55.0 Years | 54.3 Years | 52.7 Years | 53.9 Years | 53.7 Years |
| Age, Customized 65 to younger than 75 years | 19 Participants | 17 Participants | 16 Participants | 75 Participants | 23 Participants |
| Age, Customized 75 years and older | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants |
| Age, Customized Younger than 65 years | 116 Participants | 119 Participants | 118 Participants | 467 Participants | 114 Participants |
| Body Mass Index <25 kg/m^2 | 4 Participants | 12 Participants | 12 Participants | 37 Participants | 9 Participants |
| Body Mass Index ≥25 kg/m^2 | 133 Participants | 125 Participants | 123 Participants | 509 Participants | 128 Participants |
| Body Mass Index ≥27 kg/m^2 | 120 Participants | 111 Participants | 106 Participants | 452 Participants | 115 Participants |
| Body Mass Index ≥30 kg/m^2 | 77 Participants | 81 Participants | 75 Participants | 312 Participants | 79 Participants |
| Female Age 50 Years and younger | 18 Participants | 22 Participants | 22 Participants | 87 Participants | 25 Participants |
| Female Age Older than 50 years | 49 Participants | 46 Participants | 36 Participants | 167 Participants | 36 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 2 Participants | 2 Participants | 4 Participants | 9 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 1 Participants | 11 Participants | 3 Participants |
| Race/Ethnicity, Customized Black/African American | 5 Participants | 6 Participants | 4 Participants | 17 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 6 Participants | 5 Participants | 28 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 117 Participants | 118 Participants | 121 Participants | 480 Participants | 124 Participants |
| Sex: Female, Male Female | 67 Participants | 68 Participants | 58 Participants | 254 Participants | 61 Participants |
| Sex: Female, Male Male | 70 Participants | 69 Participants | 77 Participants | 292 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 84 / 137 | 87 / 137 | 77 / 137 | 83 / 135 |
| serious Total, serious adverse events | 14 / 137 | 15 / 137 | 9 / 137 | 14 / 135 |
Outcome results
Primary
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [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.
Time frame: From Baseline to Week 24
Population: All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin | Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) | -0.30 Percent | Standard Error 0.0718 |
| Dapagliflozin, 2.5 mg + Metformin | Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) | -0.67 Percent | Standard Error 0.0715 |
| Dapagliflozin, 5 mg + Metformin | Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) | -0.70 Percent | Standard Error 0.0722 |
| Dapagliflozin, 10 mg + Metformin | Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) | -0.84 Percent | Standard Error 0.0724 |
p-value: <0.0001ANCOVA
p-value: 0.0002ANCOVA
p-value: <0.0001ANCOVA
Secondary
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [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.
Time frame: From Baseline to Week 1
Population: All randomized participants who received study medication and who had nonmissing fasting plasma glucose values at baseline and Week 1 (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF]) | -6.0 mg/dL | Standard Error 1.981 |
| Dapagliflozin, 5 mg + Metformin | Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF]) | -12.0 mg/dL | Standard Error 1.976 |
| Dapagliflozin, 10 mg + Metformin | Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF]) | -16.5 mg/dL | Standard Error 2.03 |
ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [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.
Time frame: From Baseline to Week 24
Population: All randomized participants who received study medication and who had nonmissing fasting plasma glucose values at baseline and Week 24 (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF]) | -17.8 mg/dL | Standard Error 2.663 |
| Dapagliflozin, 5 mg + Metformin | Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF]) | -21.5 mg/dL | Standard Error 2.679 |
| Dapagliflozin, 10 mg + Metformin | Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF]) | -23.5 mg/dL | Standard Error 2.721 |
p-value: <0.0019ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
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])
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.
Time frame: From Baseline to Week 24
Population: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | 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]) | -0.69 Percent | Standard Error 0.0774 |
| Dapagliflozin, 5 mg + Metformin | 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]) | -0.71 Percent | Standard Error 0.0806 |
| Dapagliflozin, 10 mg + Metformin | 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]) | -0.88 Percent | Standard Error 0.0826 |
ANCOVA
p-value: 0.0004ANCOVA
p-value: <0.0001ANCOVA
Secondary
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [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.
Time frame: From Baseline to Week 24
Population: All randomized participants who received study medication, who had baseline HbA1c ≥9.0%, and who had nonmissing HbA1c values at Week 24 (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF]) | -1.21 Percent | Standard Error 0.266 |
| Dapagliflozin, 5 mg + Metformin | Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF]) | -1.37 Percent | Standard Error 0.1875 |
| Dapagliflozin, 10 mg + Metformin | Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF]) | -1.32 Percent | Standard Error 0.2595 |
ANCOVA
p-value: 0.0068ANCOVA
p-value: 0.029ANCOVA
Secondary
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])
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.
Time frame: From Baseline to Week 24
Population: 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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin | 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 0.263 |
| Dapagliflozin, 2.5 mg + Metformin | 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]) | -2.39 Kilograms | Standard Error 0.2564 |
| Dapagliflozin, 5 mg + Metformin | 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]) | -3.21 Kilograms | Standard Error 0.2661 |
| Dapagliflozin, 10 mg + Metformin | 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]) | -3.09 Kilograms | Standard Error 0.2737 |
ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [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.
Time frame: From Baseline to Week 24
Population: All randomized participants who received study medication and had nonmissing total body weights at baseline and Week 24 (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin | Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) | -0.89 Kilograms | Standard Error 0.2368 |
| Dapagliflozin, 2.5 mg + Metformin | Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) | -2.21 Kilograms | Standard Error 0.2357 |
| Dapagliflozin, 5 mg + Metformin | Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) | -3.04 Kilograms | Standard Error 0.2358 |
| Dapagliflozin, 10 mg + Metformin | Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) | -2.86 Kilograms | Standard Error 0.2392 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [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.
Time frame: From Baseline to Week 24
Population: All randomized participants who received study medication and who had HbA1c values at Baseline and Week 24 (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Metformin | Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) | 13.8 Percentage of participants |
| Dapagliflozin, 2.5 mg + Metformin | Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) | 20.7 Percentage of participants |
| Dapagliflozin, 5 mg + Metformin | Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) | 14.5 Percentage of participants |
| Dapagliflozin, 10 mg + Metformin | Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) | 25.2 Percentage of participants |
Modified logistic regression
p-value: 0.8627Modified logistic regression
p-value: 0.0149Modified logistic regression
Secondary
Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
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.
Time frame: From Baseline to Week 24
Population: All randomized participants who received study medication and were not missing baseline and Week 24 (LOCF) values
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) | 33.0 Percentage of participants |
| Dapagliflozin, 5 mg + Metformin | Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) | 37.5 Percentage of participants |
| Dapagliflozin, 10 mg + Metformin | Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) | 40.6 Percentage of participants |
p-value: 0.1775Modified logistic regression
p-value: 0.0275Modified logistic regression
p-value: 0.0062Modified logistic regression
Other Pre-specified
Mean Changes From Baseline in Seated Diastolic Blood Pressure
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.
Time frame: From Baseline to Week 102
Population: All randomized participants who received study medication. n=the number of participants not missing baseline and Week t values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | -1.0 mm Hg | Standard Error 0.929 |
| Placebo + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -0.1 mm Hg | Standard Error 0.744 |
| Placebo + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | 0.1 mm Hg | Standard Error 0.861 |
| Placebo + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -0.9 mm Hg | Standard Error 0.763 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -1.8 mm Hg | Standard Error 0.863 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -1.3 mm Hg | Standard Error 0.794 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | -0.2 mm Hg | Standard Error 0.714 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | -0.1 mm Hg | Standard Error 0.914 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -2.3 mm Hg | Standard Error 0.714 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | -1.5 mm Hg | Standard Error 0.861 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | -2.4 mm Hg | Standard Error 0.84 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -2.5 mm Hg | Standard Error 0.769 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -1.8 mm Hg | Standard Error 0.842 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | -1.2 mm Hg | Standard Error 1.041 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -1.0 mm Hg | Standard Error 0.758 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Diastolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | -1.2 mm Hg | Standard Error 0.921 |
Other Pre-specified
Mean Changes From Baseline in Seated Systolic Blood Pressure
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.
Time frame: From Baseline to Week 102
Population: All randomized participants who received study medication. n=the number of participants not missing baseline and Week t values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | 1.5 mm Hg | Standard Error 1.61 |
| Placebo + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -0.1 mm Hg | Standard Error 1.216 |
| Placebo + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -0.2 mm Hg | Standard Error 1.229 |
| Placebo + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | 1.0 mm Hg | Standard Error 1.44 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -1.6 mm Hg | Standard Error 1.38 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -2.1 mm Hg | Standard Error 1.126 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | 0.7 mm Hg | Standard Error 1.825 |
| Dapagliflozin, 2.5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | -0.1 mm Hg | Standard Error 1.281 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | -2.1 mm Hg | Standard Error 1.314 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -4.0 mm Hg | Standard Error 1.206 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | -1.1 mm Hg | Standard Error 1.412 |
| Dapagliflozin, 5 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -4.3 mm Hg | Standard Error 1.27 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 102 (n=72, 78, 88, 94) | -0.3 mm Hg | Standard Error 1.544 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 24 (n=119, 119, 122, 122) | -5.1 mm Hg | Standard Error 1.329 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 50 (n=105, 116, 111, 113) | -1.9 mm Hg | Standard Error 1.472 |
| Dapagliflozin, 10 mg + Metformin | Mean Changes From Baseline in Seated Systolic Blood Pressure | Week 12 (n=125, 129, 129, 126) | -3.0 mm Hg | Standard Error 1.23 |
Other Pre-specified
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
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.
Time frame: From Baseline to end of Long-term Period (Week 102)
Population: All randomized participants who received at least 1 dose of blinded study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | 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 | 15 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | 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 | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | 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 | 36 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 | 3 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 | 7 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 | 5 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 | 2 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 | 5 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 | 9 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | 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 | 7 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 | 33 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 | 2 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | 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 | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 | 6 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 |
| Dapagliflozin, 10 mg + Metformin | 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 |
| Dapagliflozin, 10 mg + Metformin | 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 |
| Dapagliflozin, 10 mg + Metformin | 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 | 2 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 | 45 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 | 7 Participants |
Other Pre-specified
Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
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.
Time frame: Baseline to Week 102
Population: All randomized participants who received at least 1 dose of study medication and who had nonmissing baseline and Week 102 (LOCF) values
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Placebo + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline not reported/Week 102 normal | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 abnormal | 24 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | 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 |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 normal | 11 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 not reported | 2 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 normal | 80 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 abnormal | 14 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 not reported | 6 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 normal | 20 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 not reported | 5 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 normal | 79 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 abnormal | 20 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 abnormal | 9 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 normal | 82 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 normal | 10 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 abnormal | 25 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline normal/Week 102 abnormal | 8 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline abnormal/Week 102 not reported | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) | Baseline not reported/Week 102 normal | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | 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 |
Other Pre-specified
Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
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.
Time frame: Day 1 to Week 102
Population: All randomized participants who received at least 1 dose of study medication and who had nonmissing laboratory values at baseline and Week 102.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥2.5 mg/dL | 0 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (high) | 1 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Glucose >350 mg/dL | 2 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >5*ULN | 2 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >10*ULN | 1 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 5*ULN | 0 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total <7.5 mg/dL | 4 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Magnesium, serum <1 mEq/L | 1 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total (high) | 2 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Potassium, serum ≥6 MEQ/L | 6 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum <130 mEq/L | 1 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALP elevation >1.5*ULN | 5 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum >150 mEq/L | 0 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥1.5 preRX creatinine | 2 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 3*ULN | 1 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Albumin/creatinine ratio >1800 mg/g | 2 Participants |
| Placebo + Metformin | 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 |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | AST elevation 3*ULN | 0 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >1.5*ULN | 2 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >2*ULN | 0 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (low) | 1 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hematocrit >55% | 1 Participants |
| Placebo + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hemoglobin >18 g/dL | 1 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (low) | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALP elevation >1.5*ULN | 5 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (high) | 1 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Glucose >350 mg/dL | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Albumin/creatinine ratio >1800 mg/g | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum >150 mEq/L | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >5*ULN | 2 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Magnesium, serum <1 mEq/L | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥1.5 preRX creatinine | 3 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >10*ULN | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | AST elevation 3*ULN | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥2.5 mg/dL | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hemoglobin >18 g/dL | 4 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 5*ULN | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total (high) | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total <7.5 mg/dL | 1 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >2*ULN | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Potassium, serum ≥6 MEQ/L | 3 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hematocrit >55% | 2 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum <130 mEq/L | 0 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >1.5*ULN | 1 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 3*ULN | 3 Participants |
| Dapagliflozin, 2.5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥2.5 mg/dL | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | 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 |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥1.5 preRX creatinine | 4 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hemoglobin >18 g/dL | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum <130 mEq/L | 3 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (low) | 0 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Albumin/creatinine ratio >1800 mg/g | 3 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 3*ULN | 2 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 5*ULN | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >1.5*ULN | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALP elevation >1.5*ULN | 0 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hematocrit >55% | 2 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Glucose >350 mg/dL | 0 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >5*ULN | 3 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >10*ULN | 2 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total <7.5 mg/dL | 2 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total (high) | 0 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Potassium, serum ≥6 MEQ/L | 3 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Magnesium, serum <1 mEq/L | 0 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum >150 mEq/L | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (high) | 2 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | AST elevation 3*ULN | 3 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >2*ULN | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Magnesium, serum <1 mEq/L | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Glucose >350 mg/dL | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALP elevation >1.5*ULN | 2 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum >150 mEq/L | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥2.5 mg/dL | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hematocrit >55% | 3 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | BUN ≥60 mg/d or Urea>21.4 mmol/L | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (high) | 5 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >2*ULN | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Total bilirubin elevation >1.5*ULN | 4 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Albumin/creatinine ratio >1800 mg/g | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 3*ULN | 2 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | AST elevation 3*ULN | 2 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Hemoglobin >18 g/dL | 5 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Phosphorus, inorganic (low) | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Sodium, serum <130 mEq/L | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >10*ULN | 1 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total (high) | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | ALT elevation 5*ULN | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Potassium, serum ≥6 MEQ/L | 2 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Calcium, total <7.5 mg/dL | 0 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatine kinase >5*ULN | 3 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality | Creatinine ≥1.5 preRX creatinine | 2 Participants |
Other Pre-specified
Number of Participants With Orthostatic Hypotension
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.
Time frame: From Baseline to Week 102
Population: All randomized participants who received treatment; n=the number of participants who were not missing blood pressure measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Metformin | Number of Participants With Orthostatic Hypotension | Week 12 (n=123, 128, 127, 125) | 6 Participants |
| Placebo + Metformin | Number of Participants With Orthostatic Hypotension | Baseline (n=121, 127, 124, 126) | 3 Participants |
| Placebo + Metformin | Number of Participants With Orthostatic Hypotension | Week 50 (n=103, 115, 109,112) | 10 Participants |
| Placebo + Metformin | Number of Participants With Orthostatic Hypotension | Week 102 (n=71, 76, 87, 94) | 1 Participants |
| Placebo + Metformin | Number of Participants With Orthostatic Hypotension | Week 1 (n=126, 121, 119, 114) | 28 Participants |
| Placebo + Metformin | Number of Participants With Orthostatic Hypotension | Week 24 (n=116, 114, 118, 121) | 10 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 1 (n=126, 121, 119, 114) | 26 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 24 (n=116, 114, 118, 121) | 6 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 50 (n=103, 115, 109,112) | 6 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 12 (n=123, 128, 127, 125) | 8 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Baseline (n=121, 127, 124, 126) | 4 Participants |
| Dapagliflozin, 2.5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 102 (n=71, 76, 87, 94) | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Baseline (n=121, 127, 124, 126) | 4 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 102 (n=71, 76, 87, 94) | 1 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 50 (n=103, 115, 109,112) | 7 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 12 (n=123, 128, 127, 125) | 4 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 24 (n=116, 114, 118, 121) | 5 Participants |
| Dapagliflozin, 5 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 1 (n=126, 121, 119, 114) | 21 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 102 (n=71, 76, 87, 94) | 3 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 1 (n=126, 121, 119, 114) | 19 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 12 (n=123, 128, 127, 125) | 5 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 24 (n=116, 114, 118, 121) | 3 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Orthostatic Hypotension | Week 50 (n=103, 115, 109,112) | 6 Participants |
| Dapagliflozin, 10 mg + Metformin | Number of Participants With Orthostatic Hypotension | Baseline (n=121, 127, 124, 126) | 4 Participants |