SMART: 24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy, Safety and Tolerability of Saxagliptin Compared With Acarbose When in Combination With Metformin in Patients With T2D Inadequately Controlled With Metformin Monotherapy

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02243176
• Collaborator: (none)
• Enrollment: 689
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 57.5

Study Details

Study Description

Brief Summary

SMART Study - A 24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy, Safety and Tolerability of Saxagliptin Compared with Acarbose when in Combination with Metformin in Patients with Type 2 Diabetes Mellitus (T2D) Inadequately Controlled with Metformin Monotherapy

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Saxagliptin; Drug: Acarbose	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 689 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: SMART Study - A 24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy, Safety and Tolerability of Saxagliptin Compared With Acarbose When in Combination With Metformin in Patients With Type 2 Diabetes Mellitus (T2D) Inadequately Controlled With Metformin Monotherapy
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Saxagliptin The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Drug: Saxagliptin; The dose of saxaglitpin will be 5mg oral qd.; Other Names: Onglyza
Active Comparator: Acarbose Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.	Drug: Acarbose; Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose.; Other Names: Glucobay

Outcome Measures

Primary Outcome Measures

1. Absolute Change From Baseline in HbA1c at Week 24 (DAO) [From baseline to 24 week]

   Primary Objective: Efficacy of saxagliptin plus metformin on glycemic control compared with acarbose plus metformin in patients with T2D inadequately controlled with metformin. By Measure absolute change from baseline in HbA1c at Week 24

2. Absolute Change From Baseline in HbA1c at Week 24 (DAO) [From baseline to 24 week]

   The primary endpoint was analyzed based on Per protocol analysis set as the supportive analysis.

Secondary Outcome Measures

1. Proportion (%) of Patients With Any GI Adverse Events [24 weeks]

   Secondary Objective: Assessment of any gastrointestinal adverse events of saxagliptin versus acarbose. by measure proportion (%) of patients with any gastrointestinal adverse events.

2. Proportion (%) of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c<7.0% [24 weeks]

   Secondary Objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure proportion (%) of patients achieving a therapeutic glycemic response defined as HbA1c<7.0%

3. Proportion (%) of Patients Achieving HbA1c<7.0% Without GI Adverse Events [Whole study duration]

   Secondary Objective: Assessment of any gastrointestinal adverse events of saxagliptin versus acarbose. by measure proportion (%) of patients achieving HbA1c<7.0% without GI adverse events.

4. Change From Baseline in Fasting Plasma Glucose (FPG) [From baseline to 24 week]

   Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24

5. Change From Baseline in 2H Postprandial Glucose (2HPPG) [From baseline to 24 week]

   Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24

6. Change From Baseline in HOMA-β [From baseline to 24 week]

   Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function was estimated by the Homeostasis model assessment-β (HOMA-β), which was defined as fasting insulin (mU/mL) x 20 / (fasting glucose (mmol/mL) - 3.5, body weight at week 24

7. Change From Baseline in Body Weight [From baseline to 24 week]

   Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 150 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosed with type 2 diabetes mellitus

2. Men and women (non-pregnant and using a medically approved birth-control method) aged at least 18 years at screening.

3. T2D patients treated with stable metformin monotherapy for at least 8 weeks prior to screening. Metformin dose should be ≥ 1500 mg/day (or individual maximally tolerated dose), but not more than the maximum dose specified in the label

4. HbA1c ≥ 7.5% and ≤ 11.0% at screening or within 4 weeks prior to screening (by local laboratory) and HbA1c ≥ 7.0% and ≤ 11.0% at pre-randomization visit (by central laboratory)

5. FPG ≤ 13.3 mmol/L (≤ 240 mg/dL) at pre-randomization visit (by central laboratory)

6. Able and willing to provide written informed consent and to comply with the study protocol

Exclusion Criteria:

1. Women who are pregnant, intending to become pregnant during the study period, lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.

2. Diagnosis or history of:

3. Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, eg, acromegaly or Cushing's syndrome.

4. Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.

5. Previous treatment with any dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past one year.

6. History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to dipeptidyl peptidase-4 inhibitor (DPP4) or Acarbose.

7. Treatment with any anti-diabetic medication for more than 7 consecutive days other than metformin in the last 8 weeks prior to screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Shanghai		China

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02243176
• Other Study ID Numbers: D1680L00018
• First Posted: Sep 17, 2014
• Last Update Posted: Apr 14, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by AstraZeneca: Saxagliptin; Acarbose; Type 2 Diabetes; Metformin
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Saxagliptin; Acarbose

Study Results

Participant Flow

Recruitment Details	A total of 689 patients were enrolled into this study from 35 sites in China. The enrolled patient number ranged from 10 to 58 among 24 centers, and 2 to 9 patients from eight centers, none was enrolled in 3 centers. The enrolment period was from 24 Sep 2014 to 29 Sep 2015.
Pre-assignment Detail	A total of 201 patients were enrolled but not randomized: 171 patients did not meet eligibility criteria, and 24 patients were voluntary discontinuations, two patients developed study-specific withdrawal criteria, one patient lost follow-up, and three patient failed due to other reasons

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Period Title: Overall Study
STARTED	244	244
COMPLETED	230	229
NOT COMPLETED	14	15

Baseline Characteristics

Arm/Group Title	Saxagliptin	Acarbose	Total
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.	Total of all reporting groups
Overall Participants	238	243	481
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.7 (10.51)	56.5 (10.81)	55.6 (10.69)
Sex: Female, Male (Count of Participants)
Female	91 38.2%	105 43.2%	196 40.7%
Male	147 61.8%	138 56.8%	285 59.3%
Race/Ethnicity, Customized (Number) [Number]
Asian (China Mainland)	238 100%	243 100%	481 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	166.3 (8)	165.9 (7.75)	166.1 (7.87)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	73.3 (12.61)	72.6 (12.27)	72.9 (12.43)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.4 (3.47)	26.3 (3.49)	26.3 (3.48)
Duration of diabetes mellitus (years) (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	5.1 (4.4)	5.3 (4.76)	5.2 (4.58)
Type of diabetes mellitus (Number) [Number]
Type 2	238 100%	243 100%	481 100%
Other	0 0%	0 0%	0 0%
Currently taking antidiabetic medication (Number) [Number]
Number [Participants]	238 100%	243 100%	481 100%
Any diabetes mellitus complications (Number) [Number]
No	214 89.9%	221 90.9%	435 90.4%
Yes	24 10.1%	22 9.1%	46 9.6%
Any relevant medical conditions (Number) [Number]
Yes	119 50%	125 51.4%	244 50.7%
No	65 27.3%	64 26.3%	129 26.8%
Missing	54 22.7%	54 22.2%	108 22.5%
Any current medication，excluding antidiabetic drugs (Number) [Number]
Yes	59 24.8%	73 30%	132 27.4%
No	179 75.2%	170 70%	349 72.6%
HbA1c (%) (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	8.23 (0.85)	8.16 (0.81)	8.20 (0.83)
FPG (mmol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/l]	9.01 (2.14)	8.81 (1.95)	8.90 (2.04)
2hPPG (mmol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/l]	11.17 (2.82)	10.25 (2.89)	10.7 (2.89)
Triglycerides (mmol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/l]	1.99 (1.12)	1.96 (1.38)	1.97 (1.26)
TC (mmol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/l]	4.78 (1.07)	4.82 (0.94)	4.80 (1.01)
LDL (mmol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/l]	2.73 (0.89)	2.77 (0.79)	2.75 (0.84)
HDL (mmol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/l]	1.16 (0.29)	1.2 (0.3)	1.18 (0.3)

Outcome Measures

1. Primary Outcome

Title	Absolute Change From Baseline in HbA1c at Week 24 (DAO)
Description	Primary Objective: Efficacy of saxagliptin plus metformin on glycemic control compared with acarbose plus metformin in patients with T2D inadequately controlled with metformin. By Measure absolute change from baseline in HbA1c at Week 24
Time Frame	From baseline to 24 week

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	238	243
Least Squares Mean (Standard Error) [% (HbA1c)]	-0.82 (0.06)	-0.78 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments	H01: μS-μA≥ 0.4% vs Ha1: μS-μA< 0.4%. Null hypothesis will be rejected if the upper limit of 2-sided 95% CI is below 0.4%.If the null hypothesis above (H01) is rejected, the following hypothesis will be tested to further establish superiority: H02: μS-μA≥ 0 vs Ha2: μS-μA< 0. This null hypothesis (H02) will be rejected if the upper limit of 2-sided 95% CI is below 0.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	With a total sample size of 480 patients randomized and an expected drop-out rate of 20%, the trial will be powered at 90% to establish non-inferiority for the primary endpoint, at a one-sided alpha level of 0.025, with the non-inferiority margin of 0.4%, assuming the true effects are the same between treatments. The calculation is also based on the assumption that the standard deviation for the change in HbA1c is 1.2%.
Statistical Test of Hypothesis	p-Value	0.6236
	Comments	This p value is for the hypothesis of superiority
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Mean difference=Saxagliptin - Acarbose

2. Primary Outcome

Title	Absolute Change From Baseline in HbA1c at Week 24 (DAO)
Description	The primary endpoint was analyzed based on Per protocol analysis set as the supportive analysis.
Time Frame	From baseline to 24 week

Outcome Measure Data

Analysis Population Description

The Per Protocol analysis set was a subset of the Full analysis set that included subjects who did not have significant protocol deviations that affect the study outcome. The exclusions from the PP analysis set was determined prior to database lock.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	219	204
Least Squares Mean (Standard Error) [% (HbA1c)]	-0.83 (0.06)	-0.80 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments	H01: μS-μA≥ 0.4% vs Ha1: μS-μA< 0.4%. Null hypothesis will be rejected if the upper limit of 2-sided 95% CI is below 0.4%.If the null hypothesis above (H01) is rejected, the following hypothesis will be tested to further establish superiority: H02: μS-μA≥ 0 vs Ha2: μS-μA< 0. This null hypothesis (H02) will be rejected if the upper limit of 2-sided 95% CI is below 0.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	With a total sample size of 480 patients randomized and an expected drop-out rate of 20%, the trial will be powered at 90% to establish non-inferiority for the primary endpoint, at a one-sided alpha level of 0.025, with the non-inferiority margin of 0.4%, assuming the true effects are the same between treatments. The calculation is also based on the assumption that the standard deviation for the change in HbA1c is 1.2%.
Statistical Test of Hypothesis	p-Value	0.7809
	Comments	This p value is for the hypothesis of superiority
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments	Mean difference=Saxagliptin - Acarbose

3. Secondary Outcome

Title	Proportion (%) of Patients With Any GI Adverse Events
Description	Secondary Objective: Assessment of any gastrointestinal adverse events of saxagliptin versus acarbose. by measure proportion (%) of patients with any gastrointestinal adverse events.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	238	243
NO	94.5 39.7%	75.3 31%
YES	5.5 2.3%	24.7 10.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratefied by the baseline disease severity (HbA1c < 8.0% and ≥ 8.0%)
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	RR = Saxagliptin/Acarbose

4. Secondary Outcome

Title	Proportion (%) of Patients Achieving a Therapeutic Glycemic Response Defined as HbA1c<7.0%
Description	Secondary Objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure proportion (%) of patients achieving a therapeutic glycemic response defined as HbA1c<7.0%
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	230	229
Number [percentage of participants]	38.3 16.1%	41.5 17.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5044
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	stratefied by baseline disease severity (HbA1c<8%, >=8%)
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Proportion (%) of Patients Achieving HbA1c<7.0% Without GI Adverse Events
Description	Secondary Objective: Assessment of any gastrointestinal adverse events of saxagliptin versus acarbose. by measure proportion (%) of patients achieving HbA1c<7.0% without GI adverse events.
Time Frame	Whole study duration

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	230	229
Number [percentage of participants]	37.0 15.5%	28.8 11.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0518
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratefied by the baseline disease severity (HbA1c < 8.0% and ≥ 8.0%)
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	RR = Saxagliptin/Acarbose

6. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG)
Description	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24
Time Frame	From baseline to 24 week

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	238	243
Least Squares Mean (Standard Error) [mmol/l]	-0.99 (0.13)	-1.01 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8915
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments	Mean difference=Saxagliptin - Acarbose

7. Secondary Outcome

Title	Change From Baseline in 2H Postprandial Glucose (2HPPG)
Description	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24
Time Frame	From baseline to 24 week

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	227	232
Least Squares Mean (Standard Error) [mmol/l]	-0.77 (0.176)	-1.07 (0.174)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2248
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; -0.186 to 0.791
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.249
	Estimation Comments	Mean difference=Saxagliptin - Acarbose

8. Secondary Outcome

Title	Change From Baseline in HOMA-β
Description	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function was estimated by the Homeostasis model assessment-β (HOMA-β), which was defined as fasting insulin (mU/mL) x 20 / (fasting glucose (mmol/mL) - 3.5, body weight at week 24
Time Frame	From baseline to 24 week

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	227	225
Least Squares Mean (Standard Error) [mU/mmol]	20.56 (5.932)	13.08 (5.958)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3739
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.48
	Confidence Interval	(2-Sided) 95%; -9.039 to 24.005
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.407
	Estimation Comments	Mean difference=Saxagliptin - Acarbose

9. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	Secondary objective: Effects of saxagliptin versus acarbose on the additional parameters, by measure change from baseline in fasting plasma glucose, 2h postprandial glucose, β-cell function, body weight at week 24
Time Frame	From baseline to 24 week

Outcome Measure Data

Analysis Population Description

The Full analysis set included all randomized subjects who took at least 1 randomized IP dose, and had at least 1 non-missing baseline and 1 post-baseline efficacy data assessments.

Arm/Group Title	Saxagliptin	Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.	Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
Measure Participants	238	243
Least Squares Mean (Standard Error) [kg]	-1.36 (0.18)	-2.05 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin, Acarbose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.18 to 1.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments	Mean difference=Saxagliptin - Acarbose

Adverse Events

Time Frame	Adverse Events were collected from time of signature of informed consent, throughout the treatment period. That was about 28 weeks for every subject.
Adverse Event Reporting Description	Unresolved AEs unresolved at the subject's last visit were followed up by the Investigator for as long as medically indicated, but without furtherrecording in the CRF. Below reported AEs were Treatment Emergent Adverse Events which were AEs from the first dose of investigational product to the end of follow-up.
Arm/Group Title	Saxagliptin		Acarbose
Arm/Group Description	The dose of saxaglitpin will be 5mg oral qd. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocated to this arm.		Patients who take acarbose will begin with 50mg tid for 7 days then be titrated to 100mg tid till the end of the study. A call visit (V5) will be performed at Week 1 for adverse event and reminding patients the dose titration of acrabose. An estimated total of 480 patients (240 per treatment arm) will be randomized in a 1:1 ratio to the active treatment arm and the active comparator arm. So estimated 240 patients will be allocalted to this arm.
All Cause Mortality
	Saxagliptin		Acarbose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Saxagliptin		Acarbose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/241 (2.1%)		2/244 (0.8%)
Cardiac disorders
Coronary artery disease	1/241 (0.4%)	1	1/244 (0.4%)	1
General disorders
Oedema peripheral	1/241 (0.4%)	1	0/244 (0%)	0
Hepatobiliary disorders
cholecystitis	0/241 (0%)	0	1/244 (0.4%)	1
Cholelithiasis	0/241 (0%)	0	1/244 (0.4%)	1
Hepatic function abnormal	1/241 (0.4%)	1	0/244 (0%)	0
Infections and infestations
herpes zoster	1/241 (0.4%)	1	0/244 (0%)	0
Urinary tract infection	0/241 (0%)	0	1/244 (0.4%)	1
Infection	1/241 (0.4%)	1	0/244 (0%)	0
Renal and urinary disorders
Chronic kidney disease	0/241 (0%)	0	1/244 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Saxagliptin		Acarbose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/241 (11.2%)		74/244 (30.3%)
Gastrointestinal disorders
Abdominal distension	3/241 (1.2%)	3	25/244 (10.2%)	25
Flatulence	0/241 (0%)	0	18/244 (7.4%)	18
Metabolism and nutrition disorders
Hyperlipidaemia	15/241 (6.2%)	15	14/244 (5.7%)	14
Hyperlipidaemia	9/241 (3.7%)	9	17/244 (7%)	17

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.