Evaluation of the Effect of Dapagliflozin in Combination with Metformin on Body Weight in Subjects with Type 2 Diabetes

Study identifier:D1690C00012

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 24-week,Multi-centre,Int.,Double-blind,Rand.,Parallel-group,Plac.-controlled,Phase III Study with a 78-week Ext.Per. to Evaluate the Effect of Dapagliflozin in Combination with Metformin on Body Weight in Subjects with Type2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Alone

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 3

Healthy volunteers

Study drug

Dapagliflozin, Metformin, Sitagliptin, Placebo

Sex

All

Actual Enrollment

182

Study type

Interventional

Age

30 Years - 75 Years

Date

Study Start Date: 01 Feb 2009

Primary Completion Date: 01 Jun 2010

Study Completion Date: 01 Dec 2011

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2013 by AstraZeneca

Collaborators

Bristol-Myers Squibb

Inclusion and exclusion criteria

Location

Research Site

BLAGOEVGRAD, Bulgaria

Location

Research Site

SOFIA, Bulgaria

Location

Research Site

BEROUN, Czech Republic

Location

Research Site

BRNO, Czech Republic

Location

Research Site

PRAHA, Czech Republic

Location

Research Site

SEMILY, Czech Republic

Location

Research Site

SLANY, Czech Republic

Location

Research Site

BALATONFURED, Hungary

Arms	Assigned Interventions
Experimental: A Dapagliflozin 10 mg plus Metformin	Drug: Dapagliflozin Tablet oral 10 mg total daily dose once daily 102 weeks Drug: Metformin Tablet oral 1500 - 2500 mg total daily dose 1-3 times a day104 weeks Drug: Sitagliptin Tablet oral 100 mg total daily dose once daily rescue medication
Placebo Comparator: B Placebo plus Metformin	Drug: Metformin Tablet oral 1500 - 2500 mg total daily dose 1-3 times a day104 weeks Drug: Sitagliptin Tablet oral 100 mg total daily dose once daily rescue medication Drug: Placebo Matching placebo for dapagliflozin, tablet, oral, once daily, 102 weeks

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First participant enrolled: 13 Feb 2009. Last participant completed 24 week period: 03 Jun 2010. 314 participants were enrolled, 182 were randomized in 40 centers in 5 European countries. Men aged 30-75 years and women aged 55-75 years with inadequate glycemic control (HbA1c 6.5% to 8.5%), BMI of at least 25 kg/sqm and body weight <= 120 kg.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
During a placebo lead-in period, participants were counselled on dietary and life-style modifications. The metformin dose was adjusted to open label 1500 mg/day, 2000 mg/day or 2500 mg/day. Neither gender should exceed 60% of the total number of randomized participants.

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Participant Flow: Overall Study

	Placebo plus metformin	Dapagliflozin plus metformin
STARTED	91	91^[1]
COMPLETED	86	83
NOT COMPLETED	5	8
Adverse Event	0	2
Death	0	1
Withdrawal by Subject	1	4
Poor/non-compliance	2	0
Administrative reasons by sponsor	1	0
Subject no longer meets study criteria	1	1

[1]	Of the 91 randomized participants only 89 were included in the full analysis set.

Baseline Characteristics

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

Full Analysis Set defined as all randomized participants (as randomized) who received at least one dose of double-blind study medication, who have a non-missing baseline value and at least one post-baseline efficacy value for at least one efficacy variable during double-blind treatment period.

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Baseline Measures

	Placebo plus metformin	Dapagliflozin plus metformin	Total
Number of Participants [units: Participants]	91	89	180
Age Continuous [units: Years] Mean ± Standard Deviation	60.8 ± 6.82	60.6 ± 8.16	60.7 ± 7.49
Gender, Male/Female [units: Participants]
Female	40	40	80
Male	51	49	100
Race, Customized ^[1] [units: Participants]	91	89	180
Body Weight [units: Kilogram] Mean ± Standard Deviation	90.91 ± 13.716	92.06 ± 14.128	91.48 ± 13.894
Body Mass Index [units: kg/m2] Mean ± Standard Deviation	31.68 ± 3.890	32.06 ± 3.887	31.87 ± 3.882
Glycosylated hemoglobin A1c (HbA1c) [units: Percent] Mean ± Standard Deviation	7.16 ± 0.531	7.19 ± 0.443	7.17 ± 0.489
Fasting Plasma Glucose [units: Milligram per deciliter] Mean ± Standard Deviation	149.60 ± 25.086	148.01 ± 24.650	148.82 ± 24.815

Outcome Measures

1. Primary Outcome Measure: Adjusted mean change in total body weight [ Time Frame: Baseline to Week 24 ]

Measure Type	Primary
Measure Name	Adjusted mean change in total body weight
Measure Description	To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.
Time Frame	Baseline to 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.
Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Measured Values

	Placebo plus metformin	Dapagliflozin plus metformin
Number of Participants Analyzed [units:participants]	91	89
Adjusted mean change in total body weight [units: kg] Least Squares Mean (95% Confidence Interval)	-0.88 (-1.43 to -0.34)	-2.96 (-3.51 to -2.41)

Statistical Analysis 1 for Adjusted mean change in total body weight

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-2.08
Standard Error of the mean	± 0.3885
95% Confidence Interval	( -2.84 to -1.31 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group and stratum (gender) as effects and baseline value as 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:
	Significant at alpha=0.05 (2-sided)
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Adjusted mean change in waist circumference [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted mean change in waist circumference
Measure Description	To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on waist circumference.
Time Frame	Baseline to 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.
Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Measured Values

	Placebo plus metformin	Dapagliflozin plus metformin
Number of Participants Analyzed [units:participants]	91	89
Adjusted mean change in waist circumference [units: cm] Least Squares Mean (95% Confidence Interval)	-0.99 (-1.84 to -0.13)	-2.51 (-3.38 to -1.64)

Statistical Analysis 1 for Adjusted mean change in waist circumference

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0143
Mean Difference (Final Values)^[5]	-1.52
Standard Error of the mean	± 0.6162
95% Confidence Interval	( -2.74 to -0.31 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group and stratum (gender) as effects and baseline value as 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:
	Significant at alpha=0.05 (2-sided). Results of key secondary endpoints are interpreted using Hochberg's method
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Adjusted mean change in body fat mass [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Adjusted mean change in body fat mass
Measure Description	To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on total body fat mass measured by dual energy X-ray absorptiometry.
Time Frame	Baseline to 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.
Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Measured Values

	Placebo plus metformin	Dapagliflozin plus metformin
Number of Participants Analyzed [units:participants]	79	82
Adjusted mean change in body fat mass [units: kg] Least Squares Mean (95% Confidence Interval)	-0.74 (-1.27 to -0.22)	-2.22 (-2.74 to -1.70)

Statistical Analysis 1 for Adjusted mean change in body fat mass

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0001
Mean Difference (Final Values)^[5]	-1.48
Standard Error of the mean	± 0.3731
95% Confidence Interval	( -2.22 to -0.74 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	with treatment group and stratum (gender) as effects and baseline value as 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:
	Significant at alpha=0.05 (2-sided). Results of key secondary endpoints are interpreted using Hochberg's method
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Proportion of participants with body weight decrease ≥5% [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Proportion of participants with body weight decrease ≥5%
Measure Description	To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on body weight decrease ≥5%. Least Squares Mean represents the percent of participants adjusted for body weight baseline value.
Time Frame	Baseline to 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.
Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Measured Values

	Placebo plus metformin	Dapagliflozin plus metformin
Number of Participants Analyzed [units:participants]	91	89
Proportion of participants with body weight decrease ≥5% [units: Percentage of participants] Least Squares Mean (95% Confidence Interval)	4.3 (0.1 to 8.6)	30.6 (21.1 to 40.2)

Statistical Analysis 1 for Proportion of participants with body weight decrease ≥5%

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	<0.0001
Risk Difference (RD)^[5]	26.3
Standard Error of the mean	± 5.309
95% Confidence Interval	( 15.9 to 36.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Based on methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, with adjustment for baseline value and stratum (gender).
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Significant at alpha=0.05 (2-sided). Results of key secondary endpoints are interpreted using Hochberg's method
[5]	Other relevant estimation information:
	No text entered.

5. Other Pre-specified Outcome Measure: Adjusted percent change in bone mineral density (BMD) at lumbar spine (L1-4) [ Time Frame: Baseline to Week 102 ]

Measure Type	Other Pre-specified
Measure Name	Adjusted percent change in bone mineral density (BMD) at lumbar spine (L1-4)
Measure Description	To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at lumbar spine (L1-4) as measured by Dual Energy X-ray Absorptiometry.
Time Frame	Baseline to Week 102
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.
Safety Analysis Set (all participants who received at least one dose of double-blind study medication)

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 102 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 102 weeks

Measured Values

	Placebo plus metformin	Dapagliflozin plus metformin
Number of Participants Analyzed [units:participants]	71	68
Adjusted percent change in bone mineral density (BMD) at lumbar spine (L1-4) [units: Percent] Least Squares Mean (95% Confidence Interval)	0.47 (-0.32 to 1.27)	0.69 (-0.19 to 1.57)

Statistical Analysis 1 for Adjusted percent change in bone mineral density (BMD) at lumbar spine (L1-4)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.7013
Mean Difference (Final Values)^[5]	0.22
Standard Error of the mean	± 0.5652
95% Confidence Interval	( -0.89 to 1.34 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Percent change in BMD from baseline to week 102 evaluated via longitudinal repeated measures analysis using direct likelihood.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Exploratory. Model including fixed categorical effects of treatment, week, treatment-by-week interaction, gender and rescue medication as well as continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.
[5]	Other relevant estimation information:
	Natural logarithms of baseline and week 102 values were used.

6. Other Pre-specified Outcome Measure: Adjusted percent change in bone mineral density (BMD) at femoral neck [ Time Frame: Baseline to Week 102 ]

Measure Type	Other Pre-specified
Measure Name	Adjusted percent change in bone mineral density (BMD) at femoral neck
Measure Description	To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at femoral neck as measured by Dual Energy X-ray Absorptiometry.
Time Frame	Baseline to Week 102
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.
Safety Analysis Set (all participants who received at least one dose of double-blind study medication)

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 102 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 102 weeks

Measured Values

	Placebo plus metformin	Dapagliflozin plus metformin
Number of Participants Analyzed [units:participants]	71	68
Adjusted percent change in bone mineral density (BMD) at femoral neck [units: Percent] Least Squares Mean (95% Confidence Interval)	0.09 (-0.83 to 1.01)	-0.85 (-1.85 to 0.16)

Statistical Analysis 1 for Adjusted percent change in bone mineral density (BMD) at femoral neck

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.1521
Mean Difference (Final Values)^[5]	-0.94
Standard Error of the mean	± 0.6473
95% Confidence Interval	( -2.21 to 0.35 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Percent change in BMD from baseline to week 102 evaluated via longitudinal repeated measures analysis using direct likelihood.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Exploratory. Model including fixed categorical effects of treatment, week, treatment-by-week interaction, gender and rescue medication as well as continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.
[5]	Other relevant estimation information:
	Natural logarithms of baseline and week 102 values were used.

7. Other Pre-specified Outcome Measure: Adjusted percent change in bone mineral density (BMD) at total hip [ Time Frame: Baseline to Week 102 ]

Measure Type	Other Pre-specified
Measure Name	Adjusted percent change in bone mineral density (BMD) at total hip
Measure Description	To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at total hip as measured by Dual Energy X-ray Absorptiometry.
Time Frame	Baseline to Week 102
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.
Safety Analysis Set (all participants who received at least one dose of double-blind study medication)

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 102 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 102 weeks

Measured Values

	Placebo plus metformin	Dapagliflozin plus metformin
Number of Participants Analyzed [units:participants]	71	68
Adjusted percent change in bone mineral density (BMD) at total hip [units: Percent] Least Squares Mean (95% Confidence Interval)	-0.37 (-1.00 to 0.26)	-0.82 (-1.52 to -0.12)

Statistical Analysis 1 for Adjusted percent change in bone mineral density (BMD) at total hip

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.3105
Mean Difference (Final Values)^[5]	-0.45
Standard Error of the mean	± 0.4428
95% Confidence Interval	( -1.32 to 0.43 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Percent change in BMD from baseline to week 102 evaluated via longitudinal repeated measures analysis using direct likelihood.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Exploratory. Model including fixed categorical effects of treatment, week, treatment-by-week interaction, gender and rescue medication as well as continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.
[5]	Other relevant estimation information:
	Natural logarithms of baseline and week 102 values were used.

Serious Adverse Events

Time Frame	Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Additional Description	Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Serious Adverse Events

Placebo plus metformin

Dapagliflozin plus metformin

Total, serious adverse events

# participants affected / at risk

1/91 (1.10%)

6/91 (6.59%)

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/91 (0.00%)

2/91 (2.20%)

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

0/91 (0.00%)

1/91 (1.10%)

Gastrointestinal disorders

Oesophageal varices hemorrhage¹,^†

# participants affected / at risk

0/91 (0.00%)

1/91 (1.10%)

Musculoskeletal and connective tissue disorders

Spinal osteoarthritis¹,^†

# participants affected / at risk

0/91 (0.00%)

1/91 (1.10%)

Nervous system disorders

Transient ischemic attack¹,^†

# participants affected / at risk

0/91 (0.00%)

1/91 (1.10%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/91 (0.00%)

1/91 (1.10%)

Eye disorders

Ulcerative keratitis¹,^†

# participants affected / at risk

1/91 (1.10%)

0/91 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0

Other Adverse Events

Time Frame	Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Additional Description	Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Placebo plus metformin	Placebo oral once daily plus metformin over 24 weeks
Dapagliflozin plus metformin	Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks

Other Adverse Events

Placebo plus metformin

Dapagliflozin plus metformin

Total, other (not including serious) adverse events

# participants affected / at risk

9/91 (9.89%)

7/91 (7.69%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

5/91 (5.49%)

6/91 (6.59%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

5/91 (5.49%)

1/91 (1.10%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0

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: If an Investigator requests permission to publish data from this study any such publication is to be agreed with AstraZeneca (AZ) in advance. The investigator agrees to provide AZ as soon as possible with drafts of proposed publications. Unless otherwise agreed, AZ shall have a period of 60 days from receipt of the proposed final manuscript to review it and may within such time require that submission for publication of the manuscript be delayed in order for AZ to file patent applications.

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
For participants who did not complete 24 weeks, last observation carried forward (LOCF) was used.

Results Point of Contact

Name/Title:	Eva Johnsson
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

D1690C00012 Clinical Study Report Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Contact Backup

AstraZeneca (Outside US)

001-800-236-9933

Investigators

Principal Investigator

Jan Bolinder

Dept of Endocrinology, Metabolism and Diabetes Karolinska University Hospital Huddinge Karolinska Institutet 141 86 Stockholm Sweden

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D1690C00012 Clinical Study Report Synopsis

Trial Results Summaries