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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00575588
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 891
• Locations: 95
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to assess the efficacy and tolerability of saxagliptin in addition to metformin and compare to sulphonylurea in addition with metformin.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Metformin; Drug: Sulphonylurea; Drug: Saxagliptin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 891 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 52-Week International, Multi-centre, Randomized, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination With Metformin Compared With Sulphonylurea in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy Alone.
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Saxagliptin	Drug: Metformin; open-label metformin; Drug: Saxagliptin; Saxagliptin 5 mg tablets; Other Names: Onglyza
Experimental: Glipizide	Drug: Metformin; open-label metformin; Drug: Sulphonylurea; Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks)

Outcome Measures

Primary Outcome Measures

1. Hemoglobin A1c (HbA1c) Change From Baseline to Week 52 [Baseline to 52 Weeks]

   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.

Secondary Outcome Measures

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

   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)

2. Body Weight Change From Baseline to Week 52 [Baseline, Week 52 (Last Observation Carried Forward)]

   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.

3. Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c [Week 24 to Week 52]

   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.

Other Outcome Measures

1. Hemoglobin A1c (HbA1c) Change From Baseline to Week 104 [Baseline, Week 104]

   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.

2. Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks [Baseline, Week 104]

   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)

3. Body Weight Change From Baseline to Week 104 [Baseline, Week 104]

   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.

4. Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c [Week 24 to Week 104]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with type 2 diabetes,

• Treatment with metformin alone on stable doses of 1500 mg or higher per day for at least 8 weeks prior to Visit 1,

• HbA1c >6.5% and ≤10.0%

Exclusion Criteria:

• Type 1 diabetes,

• history of diabetic ketoacidosis or hyperosmolar non-ketonic coma,

• Insulin therapy within one year of enrolment (with the exception of insulin therapy during a hospitalization or use in gestational diabetes)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Hanko		Finland
2	Research Site	Helsinki		Finland
3	Research Site	Kuopio		Finland
4	Research Site	Kuusankoski		Finland
5	Research Site	Mikkeli		Finland
6	Research Site	Oulu		Finland
7	Research Site	Tampere		Finland
8	Research Site	Aschaffenburg		Germany
9	Research Site	Berlin		Germany
10	Research Site	Dortmund		Germany
11	Research Site	Frankfurt		Germany
12	Research Site	Hamburg		Germany
13	Research Site	Hannover		Germany
14	Research Site	Mainz		Germany
15	Research Site	Mannheim		Germany
16	Research Site	Mulheim		Germany
17	Research Site	Pirna		Germany
18	Research Site	Ratzeburg		Germany
19	Research Site	Reinfeld		Germany
20	Research Site	Rhaunen		Germany
21	Research Site	Schmiedeberg		Germany
22	Research Site	Tubingen		Germany
23	Research Site	Wahlstedt		Germany
24	Research Site	Weinheim		Germany
25	Research Site	Balatonfured		Hungary
26	Research Site	Bekescsaba		Hungary
27	Research Site	Budapest		Hungary
28	Research Site	Debrecen		Hungary
29	Research Site	Gyula		Hungary
30	Research Site	Kalocsa		Hungary
31	Research Site	Kaposvar		Hungary
32	Research Site	Kecskemet		Hungary
33	Research Site	Miskolc		Hungary
34	Research Site	Mosonmagyarovar		Hungary
35	Research Site	Nyiregyhaza		Hungary
36	Research Site	Szekesfehervar		Hungary
37	Research Site	Bangalore	Karnataka	India
38	Research Site	Indore	Madhya Pradesh	India
39	Research Site	Mumbai	Mashatra	India
40	Research Site	Jaipur	Rajasthan	India
41	Research Site	Guri	Gyeonggi-do	Korea, Republic of
42	Research Site	Seongnam	Gyeonggi-do	Korea, Republic of
43	Research Site	Wonju	Kangwon-do	Korea, Republic of
44	Research Site	Incheon		Korea, Republic of
45	Research Site	Seoul		Korea, Republic of
46	Research Site	Uijeongbu-si		Korea, Republic of
47	Research Site	Beek En Donk		Netherlands
48	Research Site	Den Bosch		Netherlands
49	Research Site	Den Haag		Netherlands
50	Research Site	Deurne		Netherlands
51	Research Site	Dordrecht		Netherlands
52	Research Site	Losser		Netherlands
53	Research Site	Nijverdal		Netherlands
54	Research Site	Rijswijk		Netherlands
55	Research Site	Roelofarendsveen		Netherlands
56	Research Site	Rotterdam		Netherlands
57	Research Site	Volendam		Netherlands
58	Research Site	Bergen		Norway
59	Research Site	Elverum		Norway
60	Research Site	Flatasen		Norway
61	Research Site	Hamar		Norway
62	Research Site	Honefoss		Norway
63	Research Site	Inderoy		Norway
64	Research Site	Oslo		Norway
65	Research Site	Radal		Norway
66	Research Site	Skedsmokorset		Norway
67	Research Site	Sogndal		Norway
68	Research Site	Spikkestad		Norway
69	Research Site	Trollasen		Norway
70	Research Site	Kazan		Russian Federation
71	Research Site	Moscow		Russian Federation
72	Research Site	Nizhnii Novgorod		Russian Federation
73	Research Site	St. Petersburg		Russian Federation
74	Research Site	Yaroslavl		Russian Federation
75	Research Site	Dolny Kubin		Slovakia
76	Research Site	Kosice - Tahanovce		Slovakia
77	Research Site	Moldava Nad Bodvou		Slovakia
78	Research Site	Ruzomberok		Slovakia
79	Research Site	Trnava		Slovakia
80	Research Site	Zilina		Slovakia
81	Research Site	Annan	Dumfries and Galloway	United Kingdom
82	Research Site	Whitstable	Kent	United Kingdom
83	Research Site	Hamilton	Lanarkshire	United Kingdom
84	Research Site	Salford	Manchester	United Kingdom
85	Research Site	Crawley	West Sussex	United Kingdom
86	Research Site	Bradford-on-avon	Wiltshire	United Kingdom
87	Research Site	Blackpool		United Kingdom
88	Research Site	Coatbridge		United Kingdom
89	Research Site	Coventry		United Kingdom
90	Research Site	Glasgow		United Kingdom
91	Research Site	Motherwell		United Kingdom
92	Research Site	Newcastle		United Kingdom
93	Research Site	Sheffield		United Kingdom
94	Research Site	Ho Chi Minh City		Vietnam
95	Research Site	Ho Chi Minh		Vietnam

Sponsors and Collaborators

• AstraZeneca
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Burkhard Goke, University of Munich, Germany
• Study Director: Peter Ohman, MD, AstraZeneca
• Study Chair: Deborah Price, MSc, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00575588
• Other Study ID Numbers: D1680C00001; EudraCT number 2007-003998-55
• First Posted: Dec 18, 2007
• Last Update Posted: Mar 21, 2012
• Last Verified: Mar 1, 2012

• Keywords provided by AstraZeneca: DPP-4 Inhibitors; HbA1c; incretins
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Metformin; Saxagliptin

Study Results

Participant Flow

Pre-assignment Detail	891 participants were enrolled in the study; 33 participants did not enter the treatment period; 858 participants were randomized and treated.

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Period Title: Overall Study
STARTED	428	430
COMPLETED	165	147
NOT COMPLETED	263	283

Baseline Characteristics

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin	Total
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin	Total of all reporting groups
Overall Participants	428	430	858
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.50 (10.26)	57.59 (10.37)	57.55 (10.31)
Sex: Female, Male (Count of Participants)
Female	216 50.5%	198 46%	414 48.3%
Male	212 49.5%	232 54%	444 51.7%

Outcome Measures

1. Primary Outcome

Title	Hemoglobin A1c (HbA1c) Change From Baseline to Week 52
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

Outcome Measure Data

Analysis Population Description

Randomized participants who completed the 52 weeks of treatment had both baseline and week 52 HbA1c measurement and had no significant protocol deviations

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	293	293
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

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.053
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	428	430
Number [Percentage of Participants]	3 0.7%	36.3 8.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Between group comparison significant after controlling overall alpha of the study
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-33.2
	Confidence Interval	(2-Sided) 95%; -38.1 to -28.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Body Weight Change From Baseline to Week 52
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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	424	426
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

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Between group comparison significant after controlling overall alpha of the study
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.2
	Confidence Interval	() 95%; -2.7 to -1.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments

4. Secondary Outcome

Title	Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c
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

Outcome Measure Data

Analysis Population Description

Randomized participants who completed the 52 weeks of treatment had both baseline and week 52 HbA1c measurement and had no significant protocol deviations

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	289	293
Mean (Standard Error) [Percent]	0.001 (0.001)	0.004 (0.001)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.040
	Comments	Between group comparison significant after controlling overall alpha of the study
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.002
	Confidence Interval	(2-Sided) 95%; -0.0046 to -0.0001
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.001
	Estimation Comments

5. Other Pre-specified Outcome

Title	Hemoglobin A1c (HbA1c) Change From Baseline to Week 104
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

Outcome Measure Data

Analysis Population Description

Number of subjects with observed values at Week 104 was n=184 for saxagliptin + metformin and n=160 for glipizide + metformin

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	423	423
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

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.059
	Estimation Comments

6. Other Pre-specified Outcome

Title	Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	428	430
Number [Percentage of Participants]	3.5 0.8%	38.4 8.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-34.9
	Confidence Interval	(2-Sided) 95%; -39.8 to -30.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Other Pre-specified Outcome

Title	Body Weight Change From Baseline to Week 104
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

Outcome Measure Data

Analysis Population Description

Number of subjects with observed values at Week 104 was n=186 for saxagliptin + metformin and n=165 for glipizide + metformin

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	424	426
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

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.76
	Confidence Interval	(2-Sided) 95%; -3.32 to -2.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.286
	Estimation Comments

8. Other Pre-specified Outcome

Title	Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saxagliptin + Metformin	Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin	Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
Measure Participants	373	377
Mean (Standard Error) [Percent]	0.0041 (0.0005)	0.0076 (0.0005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Saxagliptin + Metformin, Glipizide + Metformin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.0035
	Confidence Interval	(2-Sided) 95%; -0.0048 to -0.0022
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0007
	Estimation Comments

Adverse Events

Arm/Group Title	Saxagliptin + Metformin		Glipizide + Metformin
Arm/Group Description	Saxagliptin 5 mg tablets added on to open-label metformin		Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) added on to open-label metformin
All Cause Mortality
	Saxagliptin + Metformin		Glipizide + Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Saxagliptin + Metformin		Glipizide + Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/428 (12.6%)		55/430 (12.8%)
Cardiac disorders
Atrial Fibrillation	2/428 (0.5%)		2/430 (0.5%)
Coronary Artery Disease	2/428 (0.5%)		1/430 (0.2%)
Angina Pectoris	1/428 (0.2%)		0/430 (0%)
Atrioventricular Block Complete	1/428 (0.2%)		0/430 (0%)
Cardiac Failure	1/428 (0.2%)		1/430 (0.2%)
Coronary Artery Stenosis	1/428 (0.2%)		0/430 (0%)
Myocardial Infarction	1/428 (0.2%)		1/430 (0.2%)
Myocardial Ischemia	1/428 (0.2%)		0/430 (0%)
Supraventricular Tachycardia	1/428 (0.2%)		0/430 (0%)
Ventricular Fibrillation	1/428 (0.2%)		0/430 (0%)
Angina Unstable	0/428 (0%)		2/430 (0.5%)
Arteriosclerosis Coronary Artery	0/428 (0%)		1/430 (0.2%)
Bradycardia	0/428 (0%)		1/430 (0.2%)
Coronary Artery Occlusion	0/428 (0%)		1/430 (0.2%)
Arrhythmia	1/428 (0.2%)		0/430 (0%)
Congenital, familial and genetic disorders
Hydrocele	1/428 (0.2%)		0/430 (0%)
Ear and labyrinth disorders
Deafness Bilateral	1/428 (0.2%)		0/430 (0%)
Vertigo	0/428 (0%)		1/430 (0.2%)
Endocrine disorders
Hyperthyroidism	0/428 (0%)		1/430 (0.2%)
Eye disorders
Cataract	2/428 (0.5%)		0/430 (0%)
Retinal Vein Occlusion	0/428 (0%)		1/430 (0.2%)
Gastrointestinal disorders
Inguinal Hernia	1/428 (0.2%)		1/430 (0.2%)
Abdominal Pain	0/428 (0%)		1/430 (0.2%)
Acute Abdomen	0/428 (0%)		1/430 (0.2%)
Gastroesophageal Reflux Disease	0/428 (0%)		2/430 (0.5%)
Pancreatitis	0/428 (0%)		1/430 (0.2%)
Pancreatitis Acute	0/428 (0%)		1/430 (0.2%)
Abdominal Pain Upper	1/428 (0.2%)		0/430 (0%)
Food Poisoning	1/428 (0.2%)		0/430 (0%)
Gastric Ulcer	1/428 (0.2%)		0/430 (0%)
Rectal Hemorrhage	1/428 (0.2%)		1/430 (0.2%)
Upper Gastrointestinal Hemorrhage	1/428 (0.2%)		0/430 (0%)
Gastric Hemorrhage	0/428 (0%)		1/430 (0.2%)
General disorders
Chest Pain	1/428 (0.2%)		1/430 (0.2%)
Device Malfunction	1/428 (0.2%)		0/430 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/428 (0%)		1/430 (0.2%)
Biliary Colic	0/428 (0%)		1/430 (0.2%)
Hepatitis	0/428 (0%)		1/430 (0.2%)
Cholelithiasis	1/428 (0.2%)		1/430 (0.2%)
Cholecystitis	0/428 (0%)		1/430 (0.2%)
Immune system disorders
Allergy To Arthropod Sting	1/428 (0.2%)		0/430 (0%)
Hypersensitivity	1/428 (0.2%)		1/430 (0.2%)
Infections and infestations
Anal Abscess	1/428 (0.2%)		0/430 (0%)
Pneumonia	2/428 (0.5%)		1/430 (0.2%)
Pulmonary Tuberculosis	1/428 (0.2%)		0/430 (0%)
Pyelonephritis	1/428 (0.2%)		0/430 (0%)
Helicobacter Gastritis	0/428 (0%)		1/430 (0.2%)
Superinfection	0/428 (0%)		1/430 (0.2%)
Herpes Zoster Ophthalmic	1/428 (0.2%)		0/430 (0%)
Salmonella Sepsis	1/428 (0.2%)		0/430 (0%)
Urosepsis	1/428 (0.2%)		0/430 (0%)
Biliary Tract Infection	0/428 (0%)		1/420 (0.2%)
Injury, poisoning and procedural complications
Femoral Neck Fracture	1/428 (0.2%)		0/430 (0%)
Head Injury	1/428 (0.2%)		0/430 (0%)
Meniscus Lesion	1/428 (0.2%)		0/430 (0%)
Concussion	0/428 (0%)		1/430 (0.2%)
Femur Fracture	0/428 (0%)		1/430 (0.2%)
Ligament Rupture	0/428 (0%)		1/430 (0.2%)
Open Wound	0/428 (0%)		1/430 (0.2%)
Tendon Rupture	0/428 (0%)		1/430 (0.2%)
Contusion	1/428 (0.2%)		0/430 (0%)
Lumbar Vertebral Fracture	1/428 (0.2%)		0/430 (0%)
Patella Fracture	1/428 (0.2%)		0/430 (0%)
Upper Limb Fracture	1/428 (0.2%)		0/430 (0%)
Humerus Fracture	0/428 (0%)		1/430 (0.2%)
Injury	0/428 (0%)		1/430 (0.2%)
Metabolism and nutrition disorders
Diabetes Mellitus	0/428 (0%)		1/430 (0.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	2/428 (0.5%)		1/430 (0.2%)
Arthritis	1/428 (0.2%)		0/430 (0%)
Arthropathy	1/428 (0.2%)		0/430 (0%)
Intervertebral Disc Protrusion	1/428 (0.2%)		0/430 (0%)
Jaw Cyst	1/428 (0.2%)		0/430 (0%)
Osteochondrosis	1/428 (0.2%)		1/430 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer	1/428 (0.2%)		0/430 (0%)
Colon Cancer	2/428 (0.5%)		0/430 (0%)
Metastasis To Liver	1/428 (0.2%)		0/430 (0%)
Salivary Gland Neoplasm	1/428 (0.2%)		0/430 (0%)
Acute Myeloid Leukemia	1/428 (0.2%)		0/430 (0%)
Metastases to Central Nervous System	1/428 (0.2%)		0/430 (0%)
Thyroid Cancer	1/428 (0.2%)		0/430 (0%)
Bladder Neoplasm	0/428 (0%)		1/430 (0.2%)
Bronchial Carcinoma	0/428 (0%)		1/430 (0.2%)
Colon Neoplasm	0/428 (0%)		1/430 (0.2%)
Lip Neoplasm Malignant Stage Unspecified	0/428 (0%)		1/430 (0.2%)
Lung Neoplasm malignant	0/428 (0%)		1/430 (0.2%)
Malignant Melanoma	0/428 (0%)		1/430 (0.2%)
Renal Cancer	0/428 (0%)		1/430 (0.2%)
Tumor Ulceration	0/428 (0%)		1/430 (0.2%)
Breast Cancer	0/428 (0%)		1/430 (0.2%)
Nervous system disorders
Cerebrovascular Disorder	1/428 (0.2%)		0/430 (0%)
Cerebral Ischemia	0/428 (0%)		1/430 (0.2%)
Cerebrovascular Accident	1/428 (0.2%)		1/430 (0.2%)
Ischemic Stroke	0/428 (0%)		1/430 (0.2%)
Epilepsy	1/428 (0.2%)		0/430 (0%)
Hypertensive Encephalopathy	1/428 (0.2%)		0/430 (0%)
Vertebrobasilar Insufficiency	1/428 (0.2%)		0/430 (0%)
Headache	0/428 (0%)		1/430 (0.2%)
Transient Ischemic Attack	0/428 (0%)		1/430 (0.2%)
Psychiatric disorders
Agitation	0/428 (0%)		1/430 (0.2%)
Renal and urinary disorders
Renal Failure Acute	1/428 (0.2%)		0/430 (0%)
Urinary Retention	0/428 (0%)		1/430 (0.2%)
Nephrolithiasis	1/428 (0.2%)		0/430 (0%)
Reproductive system and breast disorders
Endometrial Hyperplasia	1/428 (0.2%)		0/430 (0%)
Benign Prostatic Hyperplasia	0/428 (0%)		1/430 (0.2%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/428 (0.2%)		0/430 (0%)
Bronchitis Chronic	1/428 (0.2%)		0/430 (0%)
Dyspnea	0/428 (0%)		1/430 (0.2%)
Laryngeal Edema	0/428 (0%)		1/430 (0.2%)
Pulmonary Embolism	0/428 (0%)		1/430 (0.2%)
Vascular disorders
Aortic Aneurysm	1/428 (0.2%)		0/430 (0%)
Hypertension	0/428 (0%)		3/430 (0.7%)
Hypotension	0/428 (0%)		1/430 (0.2%)
Arteriosclerosis	0/428 (0%)		1/430 (0.2%)
Hypertensive Crisis	0/428 (0%)		3/430 (0.7%)
Circulatory Collapse	0/428 (0%)		1/430 (0.2%)
Other (Not Including Serious) Adverse Events
	Saxagliptin + Metformin		Glipizide + Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/428 (24.5%)		201/430 (46.7%)
Gastrointestinal disorders
Diarrhoea	25/428 (5.8%)		17/430 (4%)
Infections and infestations
Nasopharyngitis	46/428 (10.7%)		41/430 (9.5%)
Upper Respiratory Tract Infection	25/428 (5.8%)		16/430 (3.7%)
Metabolism and nutrition disorders
Hypoglycaemia	15/428 (3.5%)		165/430 (38.4%)
Vascular disorders
Hypertension	19/428 (4.4%)		27/430 (6.3%)

Limitations/Caveats

[Not Specified]

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.