Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from 13-April-2009 to 26-November-2009. Study completed 12-May-2010. Drug naive participants with Type 2 Diabetes Mellitus who had inadequate glycemic control with diet and exercise. Inadequate glycemic control was defined as a hemoglobin A1c (HbA1c) ≥ 7.5% and ≤ 12.0%.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Qualification: 660 completed: 28 administrative, 373 no longer met criteria, 1 lack of efficacy, 26 withdrew consent, 1 lost to follow up (LTF), 4 other. Lead-In: 649 entered; 641 completed/ randomized: 1 adverse event, 1 administrative, 4 no longer met criteria, 1 withdrew consent, 1 LTF. Treated 638: 1 LTF, 1 non-compliance, 1 withdrew consent.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks. Placebo: Metformin hydrochloride (HCl) Modified Release matching placebo tablets, once daily, 24 weeks.
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Participant Flow: Overall Study

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
STARTED	211	219	208
COMPLETED	183	188	181
NOT COMPLETED	28	31	27
Lack of Efficacy	0	1	1
Adverse Event	4	9	8
Withdrawal by Subject	11	8	11
Death	0	0	1
Lost to Follow-up	10	11	5
poor/non-compliance	2	0	0
No longer meets criteria	0	1	0
non-specified	1	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

All randomized participants who took at least one dose of double-blind study medication.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Baseline Measures

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR	Total
Number of Participants [units: Participants]	211	219	208	638
Age Continuous [units: years] Mean ± Standard Deviation	51.0 ± 10.13	51.1 ± 11.53	52.7 ± 10.38	51.6 ± 10.72
Age, Customized [units: participants]
Less than (<) 65 years	190	192	181	563
Greater than, equal to (>=) 65 and < 75 years	21	24	25	70
>= 75 years	0	3	2	5
Not Reported	0	0	0	0
Age, Customized ^[1] [units: participants]
Female <= 50 years	43	44	44	131
Female > 50 years	62	70	67	199
Gender, Male/Female [units: participants]
Female	105	114	111	330
Male	106	105	97	308
Race/Ethnicity, Customized [units: participants]
White	174	176	166	516
Black/African American	11	13	8	32
Asian	24	27	31	82
Other Race	2	3	3	8
Body Mass Index ^[2] [units: participants]
< 25 kg/m^2	20	25	21	66
>= 25 kg/m^2 - <27 kg/m^2	23	24	20	67
>= 27 kg/m^2 - <30 kg/m^2	45	39	49	133
>= 30 kg/m^2	123	131	118	372
Waist Circumference ^[3] [units: cm] Mean ± Standard Deviation	104.33 ± 13.678	103.86 ± 12.805	103.03 ± 13.224	103.75 ± 13.225
Hemoglobin A1c ^[4] [units: percent of hemoglobin] Mean ± Standard Deviation	9.09 ± 1.258	9.05 ± 1.279	9.05 ± 1.308	9.06 ± 1.280
Total Body Weight ^[5] [units: kg] Mean ± Standard Deviation	88.43 ± 19.668	88.53 ± 19.334	87.24 ± 19.423	88.08 ± 19.452
Ethnicity (NIH/OMB) ^[6] [units: Participants]
Hispanic or Latino	34	34	35	103
Not Hispanic or Latino	54	63	54	171
Unknown or Not Reported	123	122	119	364

Outcome Measures

1. Primary Outcome Measure: Adjusted Mean Change from Baseline in Hemoglobin A1c (HbA1c) at Week 24 (last observation carried forward) - Randomized Treated Participants [ Time Frame: Week 24 ]

Measure Type	Primary
Measure Name	Adjusted Mean Change from Baseline in Hemoglobin A1c (HbA1c) at Week 24 (last observation carried forward) - Randomized Treated Participants
Measure Description	Adjusted mean change in HbA1c from baseline at Week 24 (or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available, ie, last observation carried forward (LOCF) was determined. 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	Week 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
N= Number of randomized participants, who took at least 1 dose of double-blind study medication, with non-missing baseline and Week 24 (LOCF) values.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	202	216	203
Adjusted Mean Change from Baseline in Hemoglobin A1c (HbA1c) at Week 24 (last observation carried forward) - Randomized Treated Participants [units: Percent of hemoglobin] Mean (Standard Error)	-1.98 (0.0759)	-1.45 (0.0734)	-1.44 (0.0757)

Statistical Analysis 1 for Adjusted Mean Change from Baseline in Hemoglobin A1c (HbA1c) at Week 24 (last observation carried forward) - Randomized Treated Participants

Groups^[1]	Dapagliflozin + Metformin XR, Dapagliflozin
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.53
Standard Error of the mean	± 0.1056
95% Confidence Interval	( -0.74 to -0.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline HbA1c value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant. Two-sided significance level at α=0.05
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted Mean Change from Baseline in Hemoglobin A1c (HbA1c) at Week 24 (last observation carried forward) - Randomized Treated Participants

Groups^[1]	Dapagliflozin + Metformin XR, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.54
Standard Error of the mean	± 0.1072
95% Confidence Interval	( -0.75 to -0.33 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline HbA1c value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant. Two-sided significance level at α=0.05
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Adjusted Mean Change from Baseline in Hemoglobin A1c (HbA1c) at Week 24 (last observation carried forward) - Randomized Treated Participants

Groups^[1]	Dapagliflozin, Metformin XR
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
Mean Difference (Final Values)^[5]	-0.01
Standard Error of the mean	± 0.1054
95% Confidence Interval	( -0.22 to 0.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	The non-inferiority of dapagliflozin 10 mg versus metformin XR was demonstrated when the upper limit of the two-sided 95% confidence interval of the difference in change in HbA1c from baseline to Week 24 (LOCF) between dapagliflozin 10 mg and metformin XR was less than 0.35%.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline value as a covariate
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Adjusted Mean Change from Baseline in Hemoglobin A1c (HbA1c) at Week 24 (last observation carried forward) - Randomized Treated Participants

Groups^[1]	Dapagliflozin, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.9144
Mean Difference (Final Values)^[5]	-0.01
Standard Error of the mean	± 0.1054
95% Confidence Interval	( -0.22 to 0.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	When testing for superiority, significance is claimed only if dapagliflozin 10 mg is superior to metformin XR
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline HbA1c value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Adjusted Mean Change from Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted Mean Change from Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants
Measure Description	Data after rescue medication was excluded from this analysis. FPG 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. FPG 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	Week 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number analyzed = Number of randomized participants, who took at least 1 dose of double-blind study medication, with non missing baseline and Week 24 (LOCF) values.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	209	216	207
Adjusted Mean Change from Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants [units: mg/dL] Mean (Standard Error)	-60.4 (2.533)	-46.4 (2.494)	-34.8 (2.545)

Statistical Analysis 1 for Adjusted Mean Change from Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin + Metformin XR, Dapagliflozin
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-13.9
Standard Error of the mean	± 3.558
95% Confidence Interval	( -20.9 to -7.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	A hierarchical closed testing procedure was implemented to control the familywise type I error rate related to this endpoint at the two-sided 0.05 level. Statistical tests were only performed for a given secondary endpoint if all previous sequential tests versus that treatment group were also significant.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05. Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted Mean Change from Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin + Metformin XR, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-25.5
Standard Error of the mean	± 3.590
95% Confidence Interval	( -32.6 to -18.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	A hierarchical closed testing procedure was implemented to control the familywise type I error rate related to this endpoint at the two-sided 0.05 level. Statistical tests were only performed for a given secondary endpoint if all previous sequential tests versus that treatment group were also significant.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05. Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Adjusted Mean Change from Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin, Metformin XR
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	ANCOVA
Mean Difference (Final Values)^[5]	-11.6
Standard Error of the mean	± 3.566
95% Confidence Interval	( -18.6 to -4.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	The non-inferiority of dapagliflozin 10 mg versus metformin XR was demonstrated when the upper limit of the two-sided 95% confidence interval of the difference in change FPG from baseline to Week 24 (LOCF) between dapagliflozin 10 mg and metformin XR was less than 15 mg/dL.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline value as a covariate
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Adjusted Mean Change from Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0012
Mean Difference (Final Values)^[5]	-11.6
Standard Error of the mean	± 3.566
95% Confidence Interval	( -18.6 to -4.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	When testing for superiority, significance is claimed only if dapagliflozin 10 mg is superior to metformin XR
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants
Measure Description	Therapeutic glycemic response was defined as HbA1c less than 7.0%. n=Number of participants with HBA1c less than (<) 7 % at Week 24, last observation carried forward (LOCF) while N=number of randomized participants with non-missing baseline and Week 24 (LOCF) values. Percent=n/N and was adjusted for Baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Time Frame	Week 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
N=number of randomized participants with non-missing baseline and Week 24 (LOCF) values; N=202, 216, 203, respectively. n=number of responders: 92, 69, 72, respectively. n/N=percent. Percent is then adjusted for baseline HbA1c.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	202	216	203
Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants [units: Percent of participants] Number (95% Confidence Interval)	46.6 (40.1 to 53.0)	31.7 (25.7 to 37.7)	35.5 (28.8 to 41.7)

Statistical Analysis 1 for Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin + Metformin XR, Dapagliflozin
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.0012
Mean Difference (Final Values)^[5]	14.9
Standard Error of the mean	± 4.598
95% Confidence Interval	( 5.9 to 23.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The probability of response was modeled using a logistic regression model with baseline HbA1c as the covariate. Treatment group estimates of response rate were then obtained by integrating each group's modeled probability of response over the observed distribution of baseline covariate (combined across groups).
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Logistic regression based on the methodology of Zhang, Tsiatis and Davidian and Tsiatis, Davidian, Zhang and Lu, with adjustment for baseline HbA1c.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin + Metformin XR, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.0165
Mean Difference (Final Values)^[5]	11.3
Standard Error of the mean	± 4.730
95% Confidence Interval	( 2.1 to 20.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The probability of response was modeled using a logistic regression model with baseline HbA1c as the covariate. Treatment group estimates of response rate were then obtained by integrating each group's modeled probability of response over the observed distribution of baseline covariate (combined across groups).
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Logistic regression based on the methodology of Zhang, Tsiatis and Davidian and Tsiatis, Davidian, Zhang and Lu, with adjustment for baseline HbA1c.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Adjusted Mean Change from Baseline in HbA1C at Week 24 (LOCF) in Participants whose Baseline HbA1C category ≥9.0% [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted Mean Change from Baseline in HbA1C at Week 24 (LOCF) in Participants whose Baseline HbA1C category ≥9.0%
Measure Description	HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized, treated participants whose Baseline HbA1c was greater than, equal to (>=) 9.0%. 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.
Time Frame	Week 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
N= Number of randomized participants, who took at least 1 dose of double-blind study medication, with non missing baseline and Week 24 (LOCF) values, whose baseline HbA1c was >=9.0%.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	106	97	95
Adjusted Mean Change from Baseline in HbA1C at Week 24 (LOCF) in Participants whose Baseline HbA1C category ≥9.0% [units: Percent of Hemoglobin] Mean (Standard Error)	-2.59 (0.1249)	-2.14 (0.1305)	-2.05 (0.1318)

Statistical Analysis 1 for Adjusted Mean Change from Baseline in HbA1C at Week 24 (LOCF) in Participants whose Baseline HbA1C category ≥9.0%

Groups^[1]	Dapagliflozin + Metformin XR, Dapagliflozin
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0133
Mean Difference (Final Values)^[5]	-0.45
Standard Error of the mean	± 0.1807
95% Confidence Interval	( -0.81 to -0.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	A hierarchical closed testing procedure was implemented to control the familywise type I error rate related to this endpoint at the two-sided 0.05 level. Statistical testing was only performed if the dapagliflozin 10 mg plus metformin XR group was statistically significantly superior to both control groups for the primary efficacy endpoint. Tests were only performed for a given secondary endpoint if all previous sequential tests versus that treatment group were also significant.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	: treatment group as an effect and the baseline HbA1c value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05. Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Adjusted Mean Change from Baseline in HbA1C at Week 24 (LOCF) in Participants whose Baseline HbA1C category ≥9.0%

Groups^[1]	Dapagliflozin + Metformin XR, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0036
Mean Difference (Final Values)^[5]	-0.53
Standard Error of the mean	± 0.1817
95% Confidence Interval	( -0.89 to -0.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	A hierarchical closed testing procedure was implemented to control the familywise type I error rate related to this endpoint at the two-sided 0.05 level. Statistical testing was only performed if the dapagliflozin 10 mg plus metformin XR group was statistically significantly superior to both control groups for the primary efficacy endpoint. Tests were only performed for a given secondary endpoint if all previous sequential tests versus that treatment group were also significant.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline HbA1c value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05. Dapagliflozin 10 mg plus metformin XR treatment group had to be superior to both monotherapy treatment groups to be considered significant.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: The Adjusted Mean Change from Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	The Adjusted Mean Change from Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants
Measure Description	Adjusted mean change from baseline in total body weight at Week 24 (or the last post-baseline 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 was measured in kilograms (kg). 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	Week 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
N= Number of randomized participants, who took at least 1 dose of double-blind study medication, with non missing baseline and Week 24 (LOCF) values.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	209	219	208
The Adjusted Mean Change from Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants [units: kg] Mean (Standard Error)	-3.33 (0.2401)	-2.73 (0.2346)	-1.36 (0.2408)

Statistical Analysis 1 for The Adjusted Mean Change from Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin + Metformin XR, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-1.97
Standard Error of the mean	± 0.3401
95% Confidence Interval	( -2.64 to -1.30 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	A hierarchical closed testing procedure was implemented to control the familywise type I error rate related to this endpoint at the two-sided 0.05 level. Statistical testing was only performed if the dapagliflozin 10 mg plus metformin XR group was statistically significantly superior to both control groups for the primary efficacy endpoint. Tests were only performed for a given secondary endpoint if all previous sequential tests versus that treatment group were also significant.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline value as a covariate.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The Adjusted Mean Change from Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants

Groups^[1]	Dapagliflozin, Metformin XR
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-1.37
Standard Error of the mean	± 0.3362
95% Confidence Interval	( -2.03 to -0.71 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical tests were only performed for a given secondary endpoint if all previous sequential tests versus that treatment group were also significant.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	treatment group as an effect and the baseline value as a covariate
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	two-sided significance level at α=0.05
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants [ Time Frame: Day 1 of Double Blind Period to end of Week 24 Plus 30 days ]

Measure Type	Secondary
Measure Name	Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants
Measure Description	Medical Dictionary for Regulatory Activities (MedDRA), version 12.1 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. Treatment-related=having certain, probable, possible, or missing relationship to study drug as per the investigator. Events captured from baseline to last dose plus 4 days for AEs, plus 30 days for SAEs during the Double Blind 12 Week Period. Data after rescue included.
Time Frame	Day 1 of Double Blind Period to end of Week 24 Plus 30 days
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least 1 dose of double-blind study medication during the double-blind treatment period. Data after rescue were also included.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	211	219	208
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants [units: participants]
Adverse Event (AE)	126	132	118
Related Adverse Event	34	47	32
Serious Adverse Event (SAE)	3	5	4
Related SAE	0	1	1
Discontinued due to AE	4	9	8
Deaths	0	0	1
Discontinued due to SAE	0	1	1

No statistical analysis provided for Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants

7. Secondary Outcome Measure: Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants [ Time Frame: Baseline to last dose plus 4 days in 12 Week Double Blind Period ]

Measure Type	Secondary
Measure Name	Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants
Measure Description	Participants with AEs of hypoglycemia, cardiac/vascular disorders, renal impairment or failure, volume depletion (hypotension/dehydration/hypovolemia), fractures, urinary stones, and other reports suggestive of genital infection or urinary tract infection (UTI) were summarized using MedDRA version 13.0. Data after rescue included for all special AEs except hypoglycemia (excluded data after rescue). Major hypoglycemic episode: symptomatic requiring 3rd party assistance due to severe impairment in consciousness or behavior with a glucose value < 54 mg/dL and prompt recovery after glucose/glucagon; Minor: either symptomatic with glucose measurement < 63 mg/dL, regardless of need for 3rd party assistance, or asymptomatic with glucose < 63 mg/dL that does not qualify as major; Other: suggestive but not meeting criteria for major or minor.
Time Frame	Baseline to last dose plus 4 days in 12 Week Double Blind Period
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized participants who received at least one dose of study medication in the double-blind period. Data after rescue included for all AEs except hypoglycemia, which excluded data after rescue.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	211	219	208
Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants [units: participants]
Cardiac Disorder AEs	3	3	5
Vascular Disorder AEs	4	10	8
Hypoglycemia AEs (excluding data after rescue)	7	2	6
Hypoglycemia Major Episode	0	0	0
Hypoglycemia Minor Episode	1	0	1
Hypoglycemia Other Episode	6	2	5
AEs Suggestive of Genital Infection	18	28	5
AEs Suggestive of UTI	16	24	9
AEs of Renal Impairment or Failure	2	4	1
AEs of Hypotension	0	1	0
AEs of Syncope	0	1	0
AEs of Fracture	2	1	0
AEs of Urinary Stones	0	0	1

No statistical analysis provided for Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants

8. Secondary Outcome Measure: Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants
Measure Description	Measurements were taken during the Qualification and Lead-In Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 in the Double Blind Period. 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. Systolic and Diastolic pressures were measured in millimeters of mercury (mmHg). 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	Week 24
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
N=number of participants who took at least 1 dose of double-blind study medication, with non missing baseline and Week 24 values.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	182	185	179
Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants [units: mmHg] Mean (Standard Error)
Systolic (N=182, 185, 179)	-3.3 (0.947)	-4.0 (0.883)	-1.2 (1.010)
Diastolic (N=182, 185, 179)	-1.8 (0.579)	-1.9 (0.525)	0.0 (0.606)

No statistical analysis provided for Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants

9. Secondary Outcome Measure: Mean Change from Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Mean Change from Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants
Measure Description	Measurements were taken during the Qualification and Lead-In Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 in the Double Blind Period. Heart rate 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 throughout the study. Heart rate was measured in beats per minute (bpm). 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	Week 24
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
N=number of participants who took at least 1 dose of double-blind study medication, with non missing baseline and Week 24 values.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	182	185	179
Mean Change from Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants [units: bpm] Mean (Standard Error)	0.6 (0.607)	-0.1 (0.593)	0.5 (0.594)

No statistical analysis provided for Mean Change from Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants

10. Secondary Outcome Measure: Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants
Measure Description	12-Lead electrocardiograms (ECGs) were performed at entry into Lead-In Period Day -7 visit and Week 24/End of treatment visit (last observation carried forward) on participants who were supine. ECGs were assessed by the investigator. Baseline (BL) was Day -7 for this parameter. Data after rescue included.
Time Frame	Week 24
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	211	219	208
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants [units: participants]
Normal at BL, Normal at Week 24 (N=211, 219, 208)	101	107	94
Abnormal BL, Normal at Week 24 (N=211, 219, 208)	15	13	22
Normal BL, Abnormal at Week 24 (N=211, 219, 208)	18	8	9
Abnormal BL, Abnormal at Week 24 (N=211, 219, 208)	53	68	59
Normal at BL, Not Reported at Week 24	19	15	15
Abnormal at BL, Not Reported at Week 24	5	8	8
Not Reported at BL, Abnormal at Week 24	0	0	1

No statistical analysis provided for Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants

11. Secondary Outcome Measure: Number of Participants With Marked Laboratory Abnormalities (Not Including Liver Function) in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants [ Time Frame: Baseline to Week 24/end of treatment plus 4 days ]

Measure Type	Secondary
Measure Name	Number of Participants With Marked Laboratory Abnormalities (Not Including Liver Function) in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants
Measure Description	Laboratory samples: Qualification and Lead-In Periods, Day 1, Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of Double-Blind Period. Baseline (BL)=last assessment prior to start of first dose of double-blind study medication. Data after rescue included. Pretreatment (PreRX); grams per deciliter (g/dL); upper limit of normal (ULN); milliequivalent per liter (mEq/L); Units per liter (U/L), blood urea nitrogen (BUN). Marked abnormality Low (High) defined: hemoglobin <6 (>18 females or >20 males) g/dL; hematocrit <20% ( >55% females or >60% males); creatinine (>=1.5preRX, >=2.5 mg/dL); glucose <54 (>350) mg/dL; creatine kinase (>5ULN);calcium <7.5 (>=1 mg/dL from ULN and >= 0.5mg/dL from PreRX); sodium <130 or < 120 male/female (>150 mEq/L; potassium <=2.5 (>=6.0) mEq/L; bicarbonate <= 13 mEq/L; inorganic phosphorus: <=1.8 if age 17-65 or <=2.1 if age >=66, (>=5.6 if age 17-65 or >=5.1) mg/dL if age >=66; albumin <=2 (>6) g/dL; urine albumin(alb) / creatinine (creat) ratio (>1800 mg/g)
Time Frame	Baseline to Week 24/end of treatment plus 4 days
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
N=number of participants who took at least 1 dose of double-blind study medication, with non missing baseline and Week 24 values.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	209	218	207
Number of Participants With Marked Laboratory Abnormalities (Not Including Liver Function) in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants [units: participants]
Hematocrit High > 55% (N=209, 218, 206)	1	4	1
Hemoglobin High >18 g/dL(N=209, 218, 207)	5	4	1
*Creatinine >1.5PreRX (N=209, 218, 207)**	8	2	5
Glucose High > 350 mg/dL (N=209, 218, 207)	1	2	3
Albumin low or high (N=209, 218, 207)	0	0	0
Calcium Low <7.5mg/dL (N=209, 218, 207)	1	2	1
Calcium High >=1mg/dL+ULN (N=209, 218, 207)	0	2	0
Bicarbonate Low <=13mEq/L (N=209, 218, 207)	3	0	0
Potassium High >=6 mEq/L (N=209, 218, 207)	2	3	6
Sodium Low <130 mEq/L (N=209, 218, 207)	2	2	2
Sodium High >150 mEq/L (N=209, 218, 207)	5	5	2
Sodium Low <120 mEq/L (N=209, 218, 207)	0	1	0
inorganic phosphorus (high)(N=209, 218, 207)	7	13	3
Urine albumin/creat ratio (high)(N=209, 218, 206)	0	3	1

No statistical analysis provided for Number of Participants With Marked Laboratory Abnormalities (Not Including Liver Function) in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants

12. Secondary Outcome Measure: Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants [ Time Frame: Baseline to Week 24/end of treatment plus 30 days ]

Measure Type	Secondary
Measure Name	Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants
Measure Description	Safety laboratory measurements were obtained during the Qualification and Lead-In Periods and on Day 1 of the Double-Blind Period and at Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. BL was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from BL up to and including the last day of treatment plus 30 days. Liver function abnormality criteria: FDA Guidance for Industry: Premarketing Clinical Evaluation (July 2009). Data after rescue was also included. Abbreviations: Pretreatment (PreRX), upper limit of normal (ULN); greater than (>) less than (<); Units per liter (U/L), alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). Marked abnormality Low (High) defined: ALP, AST and ALT (>3ULN); bilirubin (>2ULN if PreRX <= ULN; >3ULN if PreRX > ULN); AST or ALT plus (+) bilirubin elevation: AST or ALT >3ULN and bilirubin >1.5*ULN within 14 days on or after ALT elevation.
Time Frame	Baseline to Week 24/end of treatment plus 30 days
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Measured Values

	Dapagliflozin + Metformin XR	Dapagliflozin	Metformin XR
Number of Participants Analyzed [units:participants]	210	219	208
Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants [units: participants]
*AST >3ULN (N=210, 219, 208)**	2	3	2
*AST >5ULN (N=210, 219, 208)**	0	1	1
*ALT >3ULN (N=210, 219, 208)**	2	4	7
*ALT >5ULN (N=210, 219, 208)**	0	1	2
*ALT >10ULN (N=210, 219, 208)**	0	0	1
*AST or ALT > 3ULN (N=210, 219, 208)**	3	5	7
*AST or ALT > 5ULN (N=210, 219, 208)**	0	1	2
*AST or ALT > 10ULN (N=210, 219, 208)**	0	0	1
*Total bilirubin >1.5ULN (N=210, 219, 207)**	0	2	1
AST or ALT + Bilirubin (High) (N=210, 219, 208)	0	0	1
*ALP >1.5ULN (N=210, 219, 208)**	5	4	3
*ALP >3ULN (N=210, 219, 208)**	0	0	1

No statistical analysis provided for Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants

Serious Adverse Events

Time Frame	24 Weeks plus 30 days; Day 1 of double blind treatment to last patient, last visit.
Additional Description	No text entered.

Reporting Groups

	Description
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Serious Adverse Events

Dapagliflozin

Dapagliflozin + Metformin XR

Metformin XR

Total, serious adverse events

# participants affected / at risk

5/219 (2.28%)

3/211 (1.42%)

4/208 (1.92%)

Infections and infestations

Lung abscess¹,^†

# participants affected / at risk

1/219 (0.46%)

0/211 (0.00%)

0/208 (0.00%)

Musculoskeletal and connective tissue disorders

Osteoarthritis¹,^†

# participants affected / at risk

1/219 (0.46%)

0/211 (0.00%)

0/208 (0.00%)

Cardiac disorders

Angina unstable¹,^†

# participants affected / at risk

0/219 (0.00%)

1/211 (0.47%)

0/208 (0.00%)

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

0/219 (0.00%)

1/211 (0.47%)

1/208 (0.48%)

Injury, poisoning and procedural complications

Overdose¹,^†

# participants affected / at risk

1/219 (0.46%)

0/211 (0.00%)

2/208 (0.96%)

Reproductive system and breast disorders

Rectocele¹,^†

# participants affected / at risk

1/219 (0.46%)

0/211 (0.00%)

0/208 (0.00%)

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/219 (0.00%)

0/211 (0.00%)

1/208 (0.48%)

Injury, poisoning and procedural complications

Facial bones fracture¹,^†

# participants affected / at risk

0/219 (0.00%)

1/211 (0.47%)

0/208 (0.00%)

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

0/219 (0.00%)

0/211 (0.00%)

1/208 (0.48%)

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

1/219 (0.46%)

0/211 (0.00%)

0/208 (0.00%)

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

1/219 (0.46%)

0/211 (0.00%)

0/208 (0.00%)

Gastrointestinal disorders

Proctalgia¹,^†

# participants affected / at risk

1/219 (0.46%)

0/211 (0.00%)

0/208 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary, MedDRA (12.1)

Other Adverse Events

Time Frame	24 Weeks plus 30 days; Day 1 of double blind treatment to last patient, last visit.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Dapagliflozin	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Dapagliflozin + Metformin XR	Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Metformin XR	Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks

Other Adverse Events

Dapagliflozin

Dapagliflozin + Metformin XR

Metformin XR

Total, other (not including serious) adverse events

# participants affected / at risk

32/219 (14.61%)

26/211 (12.32%)

24/208 (11.54%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

6/219 (2.74%)

15/211 (7.11%)

20/208 (9.62%)

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

17/219 (7.76%)

6/211 (2.84%)

4/208 (1.92%)

Infections and infestations

Vulvovaginal mycotic infection¹,^†

# participants affected / at risk

11/219 (5.02%)

7/211 (3.32%)

1/208 (0.48%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary, MedDRA (12.1)

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	AstraZeneca
Organization:	Clinical Trial Transparency
E-mail:	[email protected]