52-week add-on to Metformin Comparison of Saxagliptin and Sulphonylurea, With a 52-week Extension Period

This study has been completed.

Sponsor:

Collaborator:

Bristol-Myers Squibb

Information provided by (Responsible Party):

AstraZeneca

ClinicalTrials.gov Identifier:

NCT00575588

First received: December 14, 2007

Last updated: March 20, 2012

Last verified: March 2012

History of Changes

Results First Received: August 10, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Type 2 Diabetes
Interventions:	Drug: Metformin Drug: Sulphonylurea Drug: Saxagliptin

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
891 participants were enrolled in the study; 33 participants did not enter the treatment period; 858 participants were randomized and treated.

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Participant Flow: Overall Study

	Saxagliptin + Metformin	Glipizide + Metformin
STARTED	428 ^[1]	430 ^[1]
COMPLETED	165 ^[2]	147 ^[2]
NOT COMPLETED	263	283
Adverse Event	11	13
Withdrawal by Subject	27	31
Lost to Follow-up	1	3
Death	4	2
Incorrect enrollment	8	4
Study specific discontinuation criteria	203	218
Severe non-compliance to protocol	5	7
Safety reasons	2	1
Elevated triglyceride	1	0
Patient moved	1	3
Impossible to determine HbA1c	0	1

[1]	Randomized and treated
[2]	Completed 104 weeks of treatment

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Total	Total of all reporting groups

Baseline Measures

	Saxagliptin + Metformin	Glipizide + Metformin	Total
Number of Participants [units: participants]	428	430	858
Age [units: years] Mean ± Standard Deviation	57.50 ± 10.26	57.59 ± 10.37	57.55 ± 10.31
Gender [units: Participants]
Female	216	198	414
Male	212	232	444

Outcome Measures

Hide All Outcome Measures

1. Primary:

Hemoglobin A1c (HbA1c) Change From Baseline to Week 52 [ Time Frame: Baseline to 52 Weeks ]

Measure Type	Primary
Measure Title	Hemoglobin A1c (HbA1c) Change From Baseline to Week 52
Measure Description	Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 52 value minus the baseline value.
Time Frame	Baseline to 52 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.
Randomized participants who completed the 52 weeks of treatment had both baseline and week 52 HbA1c measurement and had no significant protocol deviations

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	293	293
Hemoglobin A1c (HbA1c) Change From Baseline to Week 52 [units: Percent] Mean ± Standard Error
Baseline	7.46 ± 0.045	7.53 ± 0.045
Week 52	6.74 ± 0.042	6.71 ± 0.042
Adjusted Change from Baseline to Week 52	-0.74 ± 0.038	-0.80 ± 0.038

Statistical Analysis 1 for Hemoglobin A1c (HbA1c) Change From Baseline to Week 52

Groups ^[1]	All groups
Mean Difference (Net) ^[2]	0.06
Standard Error of the mean	± 0.053
95% Confidence Interval	( -0.05 to 0.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

2. Secondary:

Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks [ Time Frame: From Baseline to Week 52 ]

Measure Type	Secondary
Measure Title	Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks
Measure Description	Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 52 weeks (Safety Analysis Set)
Time Frame	From Baseline to Week 52
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.
No text entered.

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	428	430
Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks [units: Percentage of Participants]	3	36.3

Statistical Analysis 1 for Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks

Groups ^[1]	All groups
Method ^[2]	Fisher Exact
P Value ^[3]	<0.0001
Mean Difference (Net) ^[4]	-33.2
95% Confidence Interval	( -38.1 to -28.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Between group comparison significant after controlling overall alpha of the study
[4]	Other relevant estimation information:
	No text entered.

3. Secondary:

Body Weight Change From Baseline to Week 52 [ Time Frame: Baseline, Week 52 (Last Observation Carried Forward) ]

Measure Type	Secondary
Measure Title	Body Weight Change From Baseline to Week 52
Measure Description	Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Safety Analysis Set). Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 52 (LOCF) value minus the baseline value.
Time Frame	Baseline, Week 52 (Last Observation Carried Forward)
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized participants who took at least 1 dose of double-blind treatment. To be included in the LOCF analysis, participants must have had a baseline and at least 1 post-baseline measurement

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	424	426
Body Weight Change From Baseline to Week 52 [units: kilogram] Mean ± Standard Error
Baseline	88.7 ± 0.91	88.6 ± 0.95
Week 52	87.6 ± 0.90	89.7 ± 0.99
Adjusted Change from Baseline to Week 52	-1.1 ± 0.17	1.1 ± 0.17

Statistical Analysis 1 for Body Weight Change From Baseline to Week 52

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.0001
Mean Difference (Net) ^[4]	-2.2
Standard Error of the mean	± 0.24
95% Confidence Interval	( -2.7 to -1.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Between group comparison significant after controlling overall alpha of the study
[4]	Other relevant estimation information:
	No text entered.

4. Secondary:

Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c [ Time Frame: Week 24 to Week 52 ]

Measure Type	Secondary
Measure Title	Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c
Measure Description	Mean slopes of regression of change from Week 24 to Week 52 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Per Protocol Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect.
Time Frame	Week 24 to Week 52
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.
Randomized participants who completed the 52 weeks of treatment had both baseline and week 52 HbA1c measurement and had no significant protocol deviations

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	289	293
Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c [units: Percent] Mean ± Standard Error	0.001 ± 0.001	0.004 ± 0.001

Statistical Analysis 1 for Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c

Groups ^[1]	All groups
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.040
Mean Difference (Net) ^[4]	-0.002
Standard Error of the mean	± 0.001
95% Confidence Interval	( -0.0046 to -0.0001 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Between group comparison significant after controlling overall alpha of the study
[4]	Other relevant estimation information:
	No text entered.

5. Other Pre-specified:

Hemoglobin A1c (HbA1c) Change From Baseline to Week 104 [ Time Frame: Baseline, Week 104 ]

Measure Type	Other Pre-specified
Measure Title	Hemoglobin A1c (HbA1c) Change From Baseline to Week 104
Measure Description	Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value.
Time Frame	Baseline, Week 104
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of subjects with observed values at Week 104 was n=184 for saxagliptin + metformin and n=160 for glipizide + metformin

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	423	423
Hemoglobin A1c (HbA1c) Change From Baseline to Week 104 [units: Percent] Mean ± Standard Error
Baseline	7.65 ± 0.044	7.65 ± 0.041
Week 104	7.27 ± 0.050	7.27 ± 0.046
Adjusted Change from Baseline to Week 104	-0.41 ± 0.041	-0.35 ± 0.043

Statistical Analysis 1 for Hemoglobin A1c (HbA1c) Change From Baseline to Week 104

Groups ^[1]	All groups
Mean Difference (Net) ^[2]	-0.05
Standard Error of the mean	± 0.059
95% Confidence Interval	( -0.17 to 0.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

6. Other Pre-specified:

Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks [ Time Frame: Baseline, Week 104 ]

Measure Type	Other Pre-specified
Measure Title	Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks
Measure Description	Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 104 weeks (Safety Analysis Set)
Time Frame	Baseline, Week 104
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.
No text entered.

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	428	430
Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks [units: Percentage of Participants]	3.5	38.4

Statistical Analysis 1 for Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks

Groups ^[1]	All groups
Mean Difference (Net) ^[2]	-34.9
95% Confidence Interval	( -39.8 to -30.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

7. Other Pre-specified:

Body Weight Change From Baseline to Week 104 [ Time Frame: Baseline, Week 104 ]

Measure Type	Other Pre-specified
Measure Title	Body Weight Change From Baseline to Week 104
Measure Description	Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104. Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value.
Time Frame	Baseline, Week 104
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.
Number of subjects with observed values at Week 104 was n=186 for saxagliptin + metformin and n=165 for glipizide + metformin

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	424	426
Body Weight Change From Baseline to Week 104 [units: kilograms] Mean ± Standard Error
Baseline	88.69 ± 0.905	88.57 ± 0.955
Week 104	87.47 ± 0.898	89.80 ± 0.987
Adjusted Change from Baseline to Week 104	-1.47 ± 0.200	1.29 ± 0.205

Statistical Analysis 1 for Body Weight Change From Baseline to Week 104

Groups ^[1]	All groups
Mean Difference (Net) ^[2]	-2.76
Standard Error of the mean	± 0.286
95% Confidence Interval	( -3.32 to -2.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

8. Other Pre-specified:

Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c [ Time Frame: Week 24 to Week 104 ]

Measure Type	Other Pre-specified
Measure Title	Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c
Measure Description	Mean slopes of regression of change from Week 24 to Week 104 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Full Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect.
Time Frame	Week 24 to Week 104
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.
No text entered.

Reporting Groups

	Description
Saxagliptin + Metformin	Saxagliptin 5 mg tablets added on to open-label metformin
Glipizide + Metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin

Measured Values

	Saxagliptin + Metformin	Glipizide + Metformin
Number of Participants Analyzed [units: participants]	373	377
Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c [units: Percent] Mean ± Standard Error	0.0041 ± 0.0005	0.0076 ± 0.0005

Statistical Analysis 1 for Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c

Groups ^[1]	All groups
Mean Difference (Net) ^[2]	-0.0035
Standard Error of the mean	± 0.0007
95% Confidence Interval	( -0.0048 to -0.0022 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

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

There is NOT 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: aztrial_results_posting@astrazeneca.com

No publications provided by AstraZeneca

Publications automatically indexed to this study:

Göke B, Gallwitz B, Eriksson JG, Hellqvist Å, Gause-Nilsson I. Saxagliptin vs. glipizide as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: long-term (52-week) extension of a 52-week randomised controlled trial. Int J Clin Pract. 2013 Apr;67(4):307-16.

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00575588 History of Changes
Other Study ID Numbers:	D1680C00001, EudraCT number 2007-003998-55
Study First Received:	December 14, 2007
Results First Received:	August 10, 2010
Last Updated:	March 20, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

To Top