BEYOND: Foxiga Korea Local Phase 4 Study

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02564926
• Collaborator: (none)
• Enrollment: 125
• Locations: 14
• Arms: 2
• Actual Duration (Months): 24.3
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To evaluate the effect of dapagliflozin on body composition in Korean T2DM subjects.12-month, randomised, open-label, parallel-group, multi-centre phase IV study.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Dapagliflozin; Drug: Glimepiride	Phase 4

Detailed Description

This is a 52 weeks, randomized, open-label, parallel-group, multi-centres phase IV study.

Participants will be randomized 1:1 to receive dapagliflozin 10 mg qd or glimepiride 1~2 mgqd in an open-label manner for 12 months as add-on to metformin 1000 mg.

Parallel group study design was chosen. In order maintain the practicality of the phase IV study, open label design of study drug delivery was chosen. The reading of the DXA scans will be conducted by one expert in blinded manner. Glimepiride is the most frequently used SUs in Korea and therefore this was chosen as comparator.Dapagliflozin treatment will be associated with reduction of total body FM, BW, abdominal VAT and SAT volume compared with glimepiride.

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Dapagliflozin Compared With Glimepiride on Body Composition in Patients With Type 2 Diabetes Inadequately Controlled With Metformin
• Actual Study Start Date: Jan 5, 2016
• Actual Primary Completion Date: Jan 15, 2018
• Actual Study Completion Date: Jan 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dapagliflozin Dapagliflozin 10mg + Metformin 1000mg	Drug: Dapagliflozin; Subject who will be randomized to the 'Dapagliflozin arm' will be treated with dapagliflozin 10mg + Metformin 1000 mg as Diabetes Treatment
Active Comparator: Glimepiride Glimepiriide 1-2mg + Metformin 1000mg	Drug: Glimepiride; Subject who will be randomized to the 'Glimepiride arm' will be treated with glimepiride 1-2mg + Metformin 1000 mg as Diabetes Treatment

Outcome Measures

Primary Outcome Measures

1. Adjusted Mean Changes From Baseline in Total Body Fat Mass by DXA Scan [From baseline to Week 52]

   Adjusted mean changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment

2. Adjusted Mean Changes From Baseline in Percentage of Total Body Fat Assessed by DXA Scan [From baseline to Week 52]

   Adjusted mean percent changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment

Secondary Outcome Measures

1. Adjusted Mean Change in HbA1c at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in HbA1c at Week 52

2. HbA1c <7.0% at Week 52 [52 weeks]

   HbA1c <7.0% at Week 52

3. Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52

4. Adjusted Mean Change in Total Body Weight at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in Total Body Weight at Week 52

5. Adjusted Mean Change in Waist Circumference at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in Waist Circumference at Week 52

6. Adjusted Mean Change in Body Mass Index (BMI) at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in Body Mass Index (BMI) at Week 52

7. Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52

8. Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52

9. Adjusted Mean Change in Visceral Adipose Tissue (VAT) Area at Week 52 [From baseline to Week 52]

   Adjusted Mean Change in Visceral Adipose Tissue (VAT) area at Week 52

10. Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) Area at Week 52 [From baseline to Week 52]

    Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) area at Week 52

11. Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52 [From baseline to Week 52]

    Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52

12. Adjusted Mean Change in Lean Body Mass at Week 52 [From baseline to Week 52]

    Adjusted Mean Change in Lean Body Mass at Week 52

13. Adjusted Mean Change in Adinopectin at Week 52 [From baseline to Week 52]

    Adjusted Mean Change in Adinopectin at Week 52

14. Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52 [From baseline to Week 52]

    Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adults with T2DM (Male or female, ≥ 19 and ≤ 75 yrs)

2. Patients in insufficient glycemic control (HbA1c > 7.5% and < 9.5% in recent 4 weeks)

3. Patients with an unchanged dose of metformin (≥ 1,000 mg/day) for > 8 weeks prior to randomization

4. Written informed consent

5. WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose.

• WOCBP must have a negative urine pregnancy test at screening visit WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal.

• WOCBP must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator.

Exclusion Criteria:

1. Type 1 diabetes or history of diabetic ketoacidosis

2. Pregnant or breast-feeding patients

3. eGFR < 60 mL/min/1.73 m2 (MDRD) on visit 1.

4. Indication of active liver disease (AST/ALT/total bilirubin > 3 X upper limits of normal) on visit 1.

5. Acute coronary syndrome, stroke or TIA within 3 months prior to randomization

6. Bariatric surgery within 2 years; treatment of anti-obesity drugs 3 months prior to randomization; any treatment leading to unstable body weight. (Unstable body weight is considered reliable in the judgment of the Investigator.)

7. History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time

8. History of any other malignancy within 5 years (with the exception of successfully treated non-melanoma skin cancers)

9. History of alcohol or drug abuse judged by physician within 3 months prior to randomization

10. Concomitant participation in any other clinical study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Ansan-si		Korea, Republic of	15355
2	Research Site	Changwon-si		Korea, Republic of	51353
3	Research Site	Daegu		Korea, Republic of	41931
4	Research Site	Daejeon-si		Korea, Republic of	35233
5	Research Site	Goyang-si		Korea, Republic of	10326
6	Research Site	Incheon		Korea, Republic of	21565
7	Research Site	Seongnam-si		Korea, Republic of	13620
8	Research Site	Seoul		Korea, Republic of	01830
9	Research Site	Seoul		Korea, Republic of	04401
10	Research Site	Seoul		Korea, Republic of	05278
11	Research Site	Seoul		Korea, Republic of	06273
12	Research Site	Suwon-si		Korea, Republic of	16499
13	Research Site	Uijeongbu-si		Korea, Republic of	11765
14	Research Site	Wonju-si		Korea, Republic of	220-701

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - Feb 8, 2018
• Study Protocol - Jun 7, 2016

More Information

Additional Information:

• D1690l00067_CSP_Redacted
• D1690l00067_SAP_Redacted

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02564926
• Other Study ID Numbers: D1690L00067
• First Posted: Oct 1, 2015
• Last Update Posted: Aug 20, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by AstraZeneca: DM
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Dapagliflozin; Glimepiride

Study Results

Participant Flow

Recruitment Details	First patient enrolled: 05 January 2016 Last patient last visit: 15 January 2018
Pre-assignment Detail	178 patients provided informed consent. 121 patients received study treatment and were included in the SAF population. 112 patients received study treatment and had at least one post-baseline primary efficacy assessment and were included in the FAS population (56 patients in each treatment group).

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Period Title: Overall Study
STARTED	60	61
COMPLETED	52	54
NOT COMPLETED	8	7

Baseline Characteristics

Arm/Group Title	Dapagliflozin	Glimepiride	Total
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg	Total of all reporting groups
Overall Participants	60	61	121
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (9.09)	55.7 (10.24)	55.2 (9.66)
Sex: Female, Male (Count of Participants)
Female	23 38.3%	34 55.7%	57 47.1%
Male	37 61.7%	27 44.3%	64 52.9%
Race/Ethnicity, Customized (Number) [Number]
Korean	60 100%	61 100%	121 100%

Outcome Measures

1. Primary Outcome

Title	Adjusted Mean Changes From Baseline in Total Body Fat Mass by DXA Scan
Description	Adjusted mean changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [grams]	-1485.69	1096.34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (kg)
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -3.346 to -1.819
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Adjusted Mean Change in HbA1c at Week 52
Description	Adjusted Mean Change in HbA1c at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [percentages]	-1.00	-0.54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (%)
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -0.821 to -0.094
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	HbA1c <7.0% at Week 52
Description	HbA1c <7.0% at Week 52
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Count of participants that achieved the response	27 45%	22 36.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 0.673 to 3.113
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52
Description	Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [mg/dL]	-30.94	-12.70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (mg/dL)
	Estimated Value	-18.25
	Confidence Interval	(2-Sided) 95%; -31.140 to -5.351
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Adjusted Mean Change in Total Body Weight at Week 52
Description	Adjusted Mean Change in Total Body Weight at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [kg]	-2.4	1.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (kg)
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -4.667 to -2.631
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Adjusted Mean Change in Waist Circumference at Week 52
Description	Adjusted Mean Change in Waist Circumference at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [cm]	-2.37	-0.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (cm)
	Estimated Value	-2.21
	Confidence Interval	(2-Sided) 95%; -3.785 to -0.635
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Adjusted Mean Change in Body Mass Index (BMI) at Week 52
Description	Adjusted Mean Change in Body Mass Index (BMI) at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [kg/m^2]	-0.91	0.46

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (kg/m2)
	Estimated Value	-1.37
	Confidence Interval	(2-Sided) 95%; -1.742 to -0.990
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52
Description	Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [mmHg]	-2.18	4.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (mmHg)
	Estimated Value	-6.81
	Confidence Interval	(2-Sided) 95%; -10.969 to -2.641
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52
Description	Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [mmHg]	-0.25	2.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (mmHg)
	Estimated Value	-2.61
	Confidence Interval	(2-Sided) 95%; -5.829 to 0.600
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Adjusted Mean Change in Visceral Adipose Tissue (VAT) Area at Week 52
Description	Adjusted Mean Change in Visceral Adipose Tissue (VAT) area at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [cm^2]	-16.06	1.48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (cm2)
	Estimated Value	-17.55
	Confidence Interval	(2-Sided) 95%; -28.603 to -6.489
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) Area at Week 52
Description	Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) area at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [cm^2]	-5.41	12.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (cm2)
	Estimated Value	-18.39
	Confidence Interval	(2-Sided) 95%; -27.561 to -9.218
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52
Description	Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [ratio]	-0.05	-0.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.503
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.127 to 0.063
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Adjusted Mean Change in Lean Body Mass at Week 52
Description	Adjusted Mean Change in Lean Body Mass at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [Kg]	-1.1	0.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -1.992 to -0.540
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Adjusted Mean Change in Adinopectin at Week 52
Description	Adjusted Mean Change in Adinopectin at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [ng/mL]	1746.66	1088.95

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (ng/mL)
	Estimated Value	657.71
	Confidence Interval	(2-Sided) 95%; 18.325 to 1297.101
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52
Description	Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [mg/L]	-0.51	-0.39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.756
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (mg/L)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.858 to 0.625
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Primary Outcome

Title	Adjusted Mean Changes From Baseline in Percentage of Total Body Fat Assessed by DXA Scan
Description	Adjusted mean percent changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment
Time Frame	From baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg	Glimepiriide 1-2mg + Metformin 1000mg
Measure Participants	56	56
Least Squares Mean (95% Confidence Interval) [percent change]	-1.21	0.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference (%)
	Estimated Value	-1.94
	Confidence Interval	(2-Sided) 95%; -2.807 to -1.082
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	52 weeks
Arm/Group Title	Dapagliflozin		Glimepiride
Arm/Group Description	Dapagliflozin 10mg + Metformin 1000mg		Glimepiriide 1-2mg + Metformin 1000mg
All Cause Mortality
	Dapagliflozin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/61 (0%)
Serious Adverse Events
	Dapagliflozin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/60 (10%)		6/61 (9.8%)
General disorders
Chest pain	0/60 (0%)	0	1/61 (1.6%)	1
Infections and infestations
Pyelonephritis acute	0/60 (0%)	0	1/61 (1.6%)	1
Injury, poisoning and procedural complications
Ankle fracture	0/60 (0%)	0	1/61 (1.6%)	1
Joint dislocation	0/60 (0%)	0	1/61 (1.6%)	1
Rib fracture	1/60 (1.7%)	1	0/61 (0%)	0
Splenic injury	1/60 (1.7%)	1	0/61 (0%)	0
Subdural haemorrhage	1/60 (1.7%)	1	0/61 (0%)	0
Tibia fracture	1/60 (1.7%)	1	0/61 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/60 (1.7%)	1	0/61 (0%)	0
Nervous system disorders
Migraine	0/60 (0%)	0	1/61 (1.6%)	1
Transient ischaemic attack	1/60 (1.7%)	1	0/61 (0%)	0
Trigeminal neuralgia	0/60 (0%)	0	1/61 (1.6%)	1
Psychiatric disorders
Conversion disorder	1/60 (1.7%)	2	0/61 (0%)	0
Other (Not Including Serious) Adverse Events
	Dapagliflozin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/60 (18.3%)		10/61 (16.4%)
Gastrointestinal disorders
Toothache	4/60 (6.7%)	5	1/61 (1.6%)	1
Infections and infestations
Nasopharyngitis	4/60 (6.7%)	4	2/61 (3.3%)	2
Metabolism and nutrition disorders
Hypoglycaemia	3/60 (5%)	3	7/61 (11.5%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Institution and PI shall provide the Company with copies of any materials relating to the Study that either intends to publish (or submit for publication) or make any presentations relating to, at least 30 days in advance of publication At the request of the Company, the Institution and PI shall withhold publication for a period of 90 days from the date on which the Company receives the material.