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 - SMART

Study identifier:D1680L00018

ClinicalTrials.gov identifier:NCT02243176

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 4

Healthy volunteers

Study drug

Saxagliptin, Acarbose

Sex

All

Actual Enrollment

689

Study type

Interventional

Age

18 Years - 150 Years

Date

Study Start Date: 01 Sept 2014

Primary Completion Date: 01 Sept 2015

Study Completion Date: 01 Sept 2015

Study design

Allocation: Randomized
Endpoint Classification: Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2017 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Shanghai, China

Arms	Assigned Interventions
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 Name: 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 Name: Glucobay

Arms

Assigned Interventions

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 Name: 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 Name: Glucobay

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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 Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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

Reporting Groups

	Description
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.
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.

Description

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.

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.

Participant Flow: Overall Study

	Saxagliptin	Acarbose
STARTED	244^[1]	244
COMPLETED	230	229
NOT COMPLETED	14	15
Other reason	1	2
protocol specified withdrawal critera	1	3
Protocol Violation	2	1
Withdrawal by Subject	8	7
Adverse Event	2	2

[1]	3 of the randomized subjects withdrew before taking any medication

Baseline Characteristics

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

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

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Baseline Measures

	Saxagliptin	Acarbose	Total
Number of Participants [units: Participants]	238	243	481
Age Continuous [units: Years] Mean ± Standard Deviation	54.7 ± 10.51	56.5 ± 10.81	55.6 ± 10.69
Gender, Male/Female [units: Participants]
Female	91	105	196
Male	147	138	285
Race/Ethnicity, Customized [units: Participants] Asian (China Mainland)	238	243	481
Height [units: cm] Mean ± Standard Deviation	166.3 ± 8	165.9 ± 7.75	166.1 ± 7.87
Weight [units: kg] Mean ± Standard Deviation	73.3 ± 12.61	72.6 ± 12.27	72.9 ± 12.43
BMI ^[1] [units: kg/m^2] Mean ± Standard Deviation	26.4 ± 3.47	26.3 ± 3.49	26.3 ± 3.48
Duration of diabetes mellitus (years) [units: Years] Mean ± Standard Deviation	5.1 ± 4.4	5.3 ± 4.76	5.2 ± 4.58
Type of diabetes mellitus [units: Participants]
Type 2	238	243	481
Other	0	0	0
Currently taking antidiabetic medication [units: Participants]	238	243	481
Any diabetes mellitus complications [units: Participants]
No	214	221	435
Yes	24	22	46
Any relevant medical conditions [units: Participants]
Yes	119	125	244
No	65	64	129
Missing	54	54	108
Any current medication，excluding antidiabetic drugs [units: Participants]
Yes	59	73	132
No	179	170	349
HbA1c (%) ^[2] [units: %] Mean ± Standard Deviation	8.23 ± 0.85	8.16 ± 0.81	8.20 ± 0.83
FPG ^[3] [units: mmol/l] Mean ± Standard Deviation	9.01 ± 2.14	8.81 ± 1.95	8.90 ± 2.04
2hPPG ^[4] [units: mmol/l] Mean ± Standard Deviation	11.17 ± 2.82	10.25 ± 2.89	10.7 ± 2.89
Triglycerides [units: mmol/l] Mean ± Standard Deviation	1.99 ± 1.12	1.96 ± 1.38	1.97 ± 1.26
TC ^[5] [units: mmol/l] Mean ± Standard Deviation	4.78 ± 1.07	4.82 ± 0.94	4.80 ± 1.01
LDL ^[6] [units: mmol/l] Mean ± Standard Deviation	2.73 ± 0.89	2.77 ± 0.79	2.75 ± 0.84
HDL ^[7] [units: mmol/l] Mean ± Standard Deviation	1.16 ± 0.29	1.2 ± 0.3	1.18 ± 0.3

Outcome Measures

1. Primary Outcome Measure: Absolute change from baseline in HbA1c at Week 24 (DAO) [ Time Frame: From baseline to 24 week ]

Measure Type	Primary
Measure Name	Absolute change from baseline in HbA1c at Week 24 (DAO)
Measure 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
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.
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.

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	238	243
Absolute change from baseline in HbA1c at Week 24 (DAO) [units: % (HbA1c)] Least Squares Mean (Standard Error)	-0.82 (0.06)	-0.78 (0.06)

Statistical Analysis 1 for Absolute change from baseline in HbA1c at Week 24 (DAO)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	0.6236
Mean Difference (Final Values)^[5]	-0.04
Standard Error of the mean	± 0.09
95% Confidence Interval	( -0.22 to 0.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Additional details about a non-inferiority or equivalence analysis:
	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%.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	This p value is for the hypothesis of superiority
[5]	Other relevant estimation information:
	Mean difference=Saxagliptin - Acarbose

2. Primary Outcome Measure: Absolute change from baseline in HbA1c at Week 24 (DAO) [ Time Frame: From baseline to 24 week ]

Measure Type	Primary
Measure Name	Absolute change from baseline in HbA1c at Week 24 (DAO)
Measure Description	The primary endpoint was analyzed based on Per protocol analysis set as the supportive analysis.
Time Frame	From baseline to 24 week
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.
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.

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	219	204
Absolute change from baseline in HbA1c at Week 24 (DAO) [units: % (HbA1c)] Least Squares Mean (Standard Error)	-0.83 (0.06)	-0.80 (0.07)

Statistical Analysis 1 for Absolute change from baseline in HbA1c at Week 24 (DAO)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	0.7809
Mean Difference (Final Values)^[5]	-0.03
Standard Error of the mean	± 0.09
95% Confidence Interval	( -0.21 to 0.15 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Additional details about a non-inferiority or equivalence analysis:
	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%.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	This p value is for the hypothesis of superiority
[5]	Other relevant estimation information:
	Mean difference=Saxagliptin - Acarbose

3. Secondary Outcome Measure: Proportion (%) of patients with any GI adverse events [ Time Frame: 24 weeks ]

Measure Type	Secondary
Measure Name	Proportion (%) of patients with any GI adverse events
Measure 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
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.
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.

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	238	243
Proportion (%) of patients with any GI adverse events [units: percentage of participants]
NO	94.5	75.3
YES	5.5	24.7

Statistical Analysis 1 for Proportion (%) of patients with any GI adverse events

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	<0.0001
Risk Ratio (RR)^[5]	0.22
95% Confidence Interval	( 0.12 to 0.39 )

[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:
	Stratefied by the baseline disease severity (HbA1c < 8.0% and ≥ 8.0%)
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	RR = Saxagliptin/Acarbose

4. Secondary Outcome Measure: Proportion (%) of patients achieving a therapeutic glycemic response defined as HbA1c<7.0% [ Time Frame: 24 weeks ]

Measure Type	Secondary
Measure Name	Proportion (%) of patients achieving a therapeutic glycemic response defined as HbA1c<7.0%
Measure 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
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.
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.

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	230	229
Proportion (%) of patients achieving a therapeutic glycemic response defined as HbA1c<7.0% [units: percentage of participants]	38.3	41.5

Statistical Analysis 1 for Proportion (%) of patients achieving a therapeutic glycemic response defined as HbA1c<7.0%

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.5044
Risk Ratio (RR)^[5]	0.92
95% Confidence Interval	( 0.74 to 1.15 )

[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:
	stratefied by baseline disease severity (HbA1c<8%, >=8%)
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Proportion (%) of patients achieving HbA1c<7.0% without GI adverse events [ Time Frame: Whole study duration ]

Measure Type	Secondary
Measure Name	Proportion (%) of patients achieving HbA1c<7.0% without GI adverse events
Measure 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
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.
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.

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	230	229
Proportion (%) of patients achieving HbA1c<7.0% without GI adverse events [units: percentage of participants]	37.0	28.8

Statistical Analysis 1 for Proportion (%) of patients achieving HbA1c<7.0% without GI adverse events

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.0518
Risk Ratio (RR)^[5]	1.28
95% Confidence Interval	( 0.98 to 1.67 )

[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:
	Stratefied by the baseline disease severity (HbA1c < 8.0% and ≥ 8.0%)
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	RR = Saxagliptin/Acarbose

6. Secondary Outcome Measure: Change from baseline in Fasting Plasma Glucose (FPG) [ Time Frame: From baseline to 24 week ]

Measure Type	Secondary
Measure Name	Change from baseline in Fasting Plasma Glucose (FPG)
Measure 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
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.
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.

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	238	243
Change from baseline in Fasting Plasma Glucose (FPG) [units: mmol/l] Least Squares Mean (Standard Error)	-0.99 (0.13)	-1.01 (0.13)

Statistical Analysis 1 for Change from baseline in Fasting Plasma Glucose (FPG)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	0.8915
Mean Difference (Final Values)^[5]	0.02
Standard Error of the mean	± 0.18
95% Confidence Interval	( -0.33 to 0.38 )

[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:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Mean difference=Saxagliptin - Acarbose

7. Secondary Outcome Measure: Change from baseline in 2H postprandial glucose (2HPPG) [ Time Frame: From baseline to 24 week ]

Measure Type	Secondary
Measure Name	Change from baseline in 2H postprandial glucose (2HPPG)
Measure 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
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.
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.

Reporting Groups

	Description
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.
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.

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	227	232
Change from baseline in 2H postprandial glucose (2HPPG) [units: mmol/l] Least Squares Mean (Standard Error)	-0.77 (0.176)	-1.07 (0.174)

Statistical Analysis 1 for Change from baseline in 2H postprandial glucose (2HPPG)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.2248
Mean Difference (Final Values)^[5]	0.30
Standard Error of the mean	± 0.249
95% Confidence Interval	( -0.186 to 0.791 )

[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:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[5]	Other relevant estimation information:
	Mean difference=Saxagliptin - Acarbose

8. Secondary Outcome Measure: Change from baseline in HOMA-β [ Time Frame: From baseline to 24 week ]

Measure Type	Secondary
Measure Name	Change from baseline in HOMA-β
Measure 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
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.
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.

Reporting Groups

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	227	225
Change from baseline in HOMA-β [units: mU/mmol] Least Squares Mean (Standard Error)	20.56 (5.932)	13.08 (5.958)

Statistical Analysis 1 for Change from baseline in HOMA-β

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.3739
Mean Difference (Final Values)^[5]	7.48
Standard Error of the mean	± 8.407
95% Confidence Interval	( -9.039 to 24.005 )

[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:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Mean difference=Saxagliptin - Acarbose

9. Secondary Outcome Measure: Change from baseline in body weight [ Time Frame: From baseline to 24 week ]

Measure Type	Secondary
Measure Name	Change from baseline in body weight
Measure 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
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.
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.

Reporting Groups

Description

Saxagliptin

Acarbose

Measured Values

	Saxagliptin	Acarbose
Number of Participants Analyzed [units:participants]	238	243
Change from baseline in body weight [units: kg] Least Squares Mean (Standard Error)	-1.36 (0.18)	-2.05 (0.18)

Statistical Analysis 1 for Change from baseline in body weight

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	0.0078
Mean Difference (Final Values)^[5]	0.69
Standard Error of the mean	± 0.26
95% Confidence Interval	( 0.18 to 1.19 )

[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:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	Mean difference=Saxagliptin - Acarbose

Serious 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.
Additional 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.

Reporting Groups

Description

Saxagliptin

Acarbose

Serious Adverse Events

Saxagliptin

Acarbose

Total, serious adverse events

# participants affected / at risk

5/241 (2.07%)

2/244 (0.82%)

Infections and infestations

herpes zoster¹

# participants affected / at risk

1/241 (0.41%)

0/244 (0.00%)

# events

Hepatobiliary disorders

cholecystitis¹

# participants affected / at risk

0/241 (0.00%)

1/244 (0.41%)

# events

Hepatobiliary disorders

Cholelithiasis¹

# participants affected / at risk

0/241 (0.00%)

1/244 (0.41%)

# events

Renal and urinary disorders

Chronic kidney disease¹

# participants affected / at risk

0/241 (0.00%)

1/244 (0.41%)

# events

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

0/241 (0.00%)

1/244 (0.41%)

# events

Cardiac disorders

Coronary artery disease¹

# participants affected / at risk

1/241 (0.41%)

1/244 (0.41%)

# events

General disorders

Oedema peripheral¹
The SOC term was reported as "General disorders and administration site conditions" in study results.

# participants affected / at risk

1/241 (0.41%)

0/244 (0.00%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹

# participants affected / at risk

1/241 (0.41%)

0/244 (0.00%)

# events

Infections and infestations

Infection¹

# participants affected / at risk

1/241 (0.41%)

0/244 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDra 18.0

Other 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.
Additional 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.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

Description

Saxagliptin

Acarbose

Other Adverse Events

Saxagliptin

Acarbose

Total, other (not including serious) adverse events

# participants affected / at risk

27/241 (11.20%)

74/244 (30.33%)

Metabolism and nutrition disorders

Hyperlipidaemia¹

# participants affected / at risk

15/241 (6.22%)

14/244 (5.74%)

# events

Metabolism and nutrition disorders

Hyperlipidaemia¹

# participants affected / at risk

9/241 (3.73%)

17/244 (6.97%)

# events

Gastrointestinal disorders

Abdominal distension¹

# participants affected / at risk

3/241 (1.24%)

25/244 (10.25%)

# events

Gastrointestinal disorders

Flatulence¹

# participants affected / at risk

0/241 (0.00%)

18/244 (7.38%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDra 18.0

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: