Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin

Study identifier:CV181-057

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicenter, Randomized, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Insulin Alone or on Insulin in Combination With Metformin

Medical condition

Type 2 Diabetes

Phase

Phase 3

Healthy volunteers

Study drug

Saxagliptin, 5 mg + insulin, Placebo + insulin

Sex

All

Actual Enrollment

455

Study type

Interventional

Age

18 Years - 78 Years

Date

Study Start Date: 01 Nov 2008

Primary Completion Date: 01 Apr 2010

Study Completion Date: 01 Apr 2010

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 May 2015 by AstraZeneca Pharmaceuticals

Collaborators

AstraZeneca

Inclusion and exclusion criteria

Location

Local Institution

Montpellier Cedex 5, France, 34295

Location

Local Institution

Valenciennes, France, 59300

Location

Danny W. Jackson P.A.

Rolling Fork, MS, United States, 39159

Location

Panhandle Family Care Assoc. & Coastal Palms Res. Grp Inc.

Marianna, FL, United States, 32446

Location

Ritchken & First M.D.'S

San Diego, CA, United States, 92117

Location

Aurora Advanced Healthcare

Milwaukee, WI, United States, 53209

Location

Local Institution

Wroclaw, Poland, 50-088

Location

Local Institution

Elblag, Poland, 82-300

Arms	Assigned Interventions
Experimental: Saxagliptin, 5 mg + insulin Saxagliptin, 5 mg, plus insulin, administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin	Drug: Saxagliptin, 5 mg + insulin Saxagliptin, 5-mg tablets (plus stable insulin dose), given orally once daily (24 weeks short-term, 28 weeks long-term); participants stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue) Other Name: BMS-477118
Placebo Comparator: Placebo + insulin Placebo administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin	Drug: Placebo + insulin Placebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin

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
Of 455 participants randomized, 402 received treatment and completed the 24-week phase. Two participants were mistakenly identified as not completing the short-term (ST) treatment period, although they did. The discrepancy was identified after the ST phase database lock. In reality, 404 completed the ST phase.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Participant Flow for 2 periods

Period 1: Period 1: Short-term (24-week) phase

	Saxagliptin, 5 mg + insulin	Placebo + insulin
STARTED	304	151
COMPLETED	268^[1]	134
NOT COMPLETED	36	17
Lack of Efficacy	3	2
Adverse Event	6	3
Withdrawal by Subject	13	5
Death	1	0
Lost to Follow-up	3	5
Poor compliance or noncompliance	5	1
No longer meets study criteria	5	0
Not specified	0	1

[1]	Does not include 2 who completed Period 1 but were erroneously reported in the CSR as noncompleters.

Period 2: Period 2: Long-term (52-week) phase

	Saxagliptin, 5 mg + insulin	Placebo + insulin
STARTED	268^[1]	134
COMPLETED	246	125
NOT COMPLETED	22	9
Lack of Efficacy	1	0
Adverse Event	4	0
Withdrawal by Subject	4	2
Lost to Follow-up	1	1
Poor or noncompliance	5	2
Pregnancy	1	0
No longer meets study criteria	5	4
Not specified	1	0

[1]	270 participants completed short-term phase; 2 of these did not enter long-term phase.

Baseline Characteristics

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

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Baseline Measures

	Saxagliptin, 5 mg + insulin	Placebo + insulin	Total
Number of Participants [units: Participants]	304	151	455
Age, Customized [units: years] Median ( Full Range )	58 (18 to 77)	58 (30 to 77)	58 (18 to 77)
Age, Customized [units: participants]
Younger than 65 years	233	118	351
65 years to younger than 75 years	65	30	95
75 years and older	6	3	9
Age, Customized [units: Years] Mean ± Standard Deviation	57.2 ± 9.43	57.3 ± 9.27	57.2 ± 9.37
Gender, Male/Female [units: participants]
Female	184	83	267
Male	120	68	188
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0	0	0
Asian	40	19	59
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	13	9	22
White	237	118	355
More than one race	0	0	0
Unknown or Not Reported	14	5	19

Outcome Measures

1. Primary Outcome Measure: Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF]) [ Time Frame: Baseline to Week 24 ]

Measure Type	Primary
Measure Name	Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])
Measure Description	Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use
Time Frame	Baseline to Week 24
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 received at least 1 dose of double-blind study medication. Participants must also have had both a baseline and at least 1 postrandomization measurement in the 24- and 52-week periods.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	300	149
Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF]) [units: Percentage of change] Mean (Standard Error)	-0.73 (0.054)	-0.32 (0.074)

Statistical Analysis 1 for Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])

Groups^[1]	Saxagliptin, 5 mg + insulin
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001
Mean Difference (Final Values)^[5]	-0.41
Standard Error of the mean	± 0.089
95% Confidence Interval	( -0.59 to -0.24 )

[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:
	Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[5]	Other relevant estimation information:
	ANCOVA model: difference between week t and baseline values = baseline values + treatment + metformin use

2. Secondary Outcome Measure: Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT) [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)
Measure Description	An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal
Time Frame	Baseline to Week 24
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.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	258	122
Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT) [units: mg*min/dL] Mean (Standard Error)	-4548.5 (687.65)	-718.8 (981.63)

Statistical Analysis 1 for Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0011
Mean Difference (Final Values)^[5]	-3829.8
Standard Error of the mean	± 1165.99
95% Confidence Interval	( -6122.4 to -1537.1 )

[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:
	Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[5]	Other relevant estimation information:
	ANCOVA model: difference between week t and baseline values = baseline values + treatment + metformin use

3. Secondary Outcome Measure: Change From Baseline in 120-minute PPG Values During an MTT [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Change From Baseline in 120-minute PPG Values During an MTT
Measure Description	An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal.
Time Frame	Baseline to Week 24
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.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	262	129
Change From Baseline in 120-minute PPG Values During an MTT [units: mg/dL] Mean (Standard Error)	-27.2 (4.35)	-4.2 (6.08)

Statistical Analysis 1 for Change From Baseline in 120-minute PPG Values During an MTT

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0016
Mean Difference (Final Values)^[5]	-23.0
Standard Error of the mean	± 7.24
95% Confidence Interval	( -37.2 to -8.7 )

[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:
	Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[5]	Other relevant estimation information:
	ANCOVA model: difference between week t and baseline values = baseline values + treatment + metformin use

4. Secondary Outcome Measure: Change From Baseline in Fasting Plasma Glucose Values [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Fasting Plasma Glucose Values
Measure Description
Time Frame	Baseline to Week 24
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.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	300	149
Change From Baseline in Fasting Plasma Glucose Values [units: mg/dL] Mean (Standard Error)	-10.1 (2.87)	-6.1 (3.98)

Statistical Analysis 1 for Change From Baseline in Fasting Plasma Glucose Values

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.3958
Mean Difference (Final Values)^[5]	-4.02
Standard Error of the mean	± 4.732
95% Confidence Interval	( -13.32 to 5.28 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[5]	Other relevant estimation information:
	ANCOVA model: difference between week t and baseline values = baseline values + treatment + metformin use

5. Secondary Outcome Measure: Percentage of Participants Achieving a Therapeutic Glycemic Response [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving a Therapeutic Glycemic Response
Measure Description	Therapeutic glycemic response is defined as an A1C<7%. Significance was not interpreted with a p value.
Time Frame	Baseline to Week 24
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 received at least 1 dose of double-blind study medication. Participants must also have had both a baseline and at least 1 postrandomization measurement in the 24-week period.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	300	149
Percentage of Participants Achieving a Therapeutic Glycemic Response [units: Percentage of participants]	17.3	6.7

No statistical analysis provided for Percentage of Participants Achieving a Therapeutic Glycemic Response

6. Secondary Outcome Measure: Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF) [ Time Frame: Baseline to Week 24 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)
Measure Description	Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline.
Time Frame	Baseline to Week 24
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 received at least 1 dose of double-blind study medication. Participants must also have had both a baseline and at least 1 postrandomization measurement in the 24-week period.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	299	151
Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF) [units: Units] Mean (Standard Error)	1.71 (0.704)	5.01 (0.970)

Statistical Analysis 1 for Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)

Groups^[1]	Saxagliptin, 5 mg + insulin
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
Mean Difference (Final Values)^[5]	-3.3
Standard Error of the mean	± 1.16
95% Confidence Interval	( -5.6 to -1.1 )

[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:
	Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[5]	Other relevant estimation information:
	ANCOVA model: difference between week t and baseline values = baseline values + treatment + metformin use

7. Other Pre-specified Outcome Measure: Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results [ Time Frame: Baseline to Week 52 ]

Measure Type	Other Pre-specified
Measure Name	Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results
Measure Description	ECG abnormalities included those in nonspecific "other" categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions.
Time Frame	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.
Participants who had normal ECG findings at baseline and who received at least 1 dose of study medication.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	153	75
Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results [units: Participants]	15	11

No statistical analysis provided for Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results

8. Other Pre-specified Outcome Measure: Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) [ Time Frame: Baseline and Weeks 24 and 52 ]

Measure Type	Other Pre-specified
Measure Name	Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)
Measure Description	Absolute lymphocyte count=value*10^3 c/uL
Time Frame	Baseline and Weeks 24 and 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.
All participants who received at least 1 dose of double-blind study medication.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	304	151
Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) [units: Participants]
Baseline <= 0.75; Week 24 <= 0.75	0	0
Baseline <= 0.75; Week 24 >0.75- <= 5.00	0	2
Baseline <= 0.75; Week 24 >5.00	0	0
Baseline >0.75- <= 5.00; Week 24 <= 0.75	1	0
Baseline >0.75- <= 5.00; Week 24 >0.75- <= 5.00	293	148
Baseline >0.75- <= 5.00; Week 24 >5.00	1	0
Baseline >5.00; Week 24 <= 0.75	0	0
Baseline >5.00; Week 24 >0.75- <= 5.00	0	0
Baseline >5.00; Week 24 >5.00	1	0
Baseline <= 0.75; Week 52 <= 0.75	0	0
Baseline <= 0.75; Week 52 >0.75- <= 5.00	0	2
Baseline <= 0.75; Week 52 >5.00	0	0
Baseline >0.75- <= 5.00; Week 52 <= 0.75	0	0
Baseline >0.75- <= 5.00; Week 52 >0.75- <= 5.00	295	147
Baseline >0.75- <= 5.00; Week 52 >5.00	0	1
Baseline >5.00; Week 52 <= 0.75	0	0
Baseline >5.00; Week 52 >0.75- <= 5.00	0	0
Baseline >5.00; Week 52 >5.00	1	0

No statistical analysis provided for Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)

9. Other Pre-specified Outcome Measure: Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs [ Time Frame: Baseline to Week 52, continuously ]

Measure Type	Other Pre-specified
Measure Name	Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs
Measure Description	An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time Frame	Baseline to Week 52, continuously
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.
All participants who received at least 1 dose of double-blind study medication.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	304	151
Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs [units: Participants]
At least 1 AE	202	108
At least 1 treatment-related AE	56	34
Deaths	2	0
At least 1 SAE	25	13
At least 1 treatment-related SAE	3	0
Discontinuations due to SAEs	4	0
Discontinuations due to AEs	9	3

No statistical analysis provided for Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs

10. Other Pre-specified Outcome Measure: Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings [ Time Frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52 ]

Measure Type	Other Pre-specified
Measure Name	Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings
Measure Description
Time Frame	Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 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.
All participants who received at least 1 dose of double-blind study medication.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	304	151
Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings [units: mm Hg] Number (95% Confidence Interval)
Systolic blood pressure (Week 2) (n=294, 147)	-1.0 (-2.3 to 0.4)	2.3 (-0.0 to 4.6)
Systolic blood pressure (Week 4) (n=293, 144)	-1.2 (-2.6 to 0.2)	0.0 (-2.3 to 2.4)
Systolic blood pressure (Week 6) (n=280, 141)	-0.8 (-2.4 to 0.7)	1.0 (-1.2 to 3.2)
Systolic blood pressure (Week 8) (n=290, 142)	-0.8 (-2.4 to 0.8)	2.4 (-0.2 to 4.9)
Systolic blood pressure (Week 12) (n=286, 144)	-1.7 (-3.2 to -0.2)	2.2 (0.0 to 4.3)
Systolic blood pressure (Week 16) (n=278, 139)	-1.2 (-2.9 to 0.5)	1.1 (-1.1 to 3.3)
Systolic blood pressure (Week 20) (n=276, 137)	-0.6 (-2.0 to 0.9)	1.3 (-1.0 to 3.7)
Systolic blood pressure (Week 24) (n=273, 134)	-1.5 (-3.2 to 0.1)	-0.1 (-2.2 to 2.0)
Systolic blood pressure (Week 28) (n=264, 132)	-1.4 (-3.0 to 0.1)	1.8 (-0.6 to 4.2)
Systolic blood pressure (Week 36) (n=261, 129)	-0.7 (-2.4 to 1.1)	3.6 (1.2 to 6.0)
Systolic blood pressure (Week 44) (n=250, 125)	-0.6 (-2.2 to 1.0)	2.6 (0.4 to 4.8)
Systolic blood pressure (Week 52) (n=246, 125)	0.0 (-1.7 to 1.7)	1.0 (-1.3 to 3.3)
Diastolic blood pressure (Week 2) (n=294, 147)	0.1 (-0.9 to 1.0)	1.4 (-0.0 to 2.8)
Diastolic blood pressure (Week 4) (n=293, 144)	0.0 (-1.0 to 1.1)	1.8 (0.4 to 3.2)
Diastolic blood pressure (Week 6) (n=280, 141)	0.0 (-1.0 to 1.1)	0.3 (-1.1 to 1.8)
Diastolic blood pressure (Week 8) (n=290, 142)	-0.5 (-1.5 to 0.4)	2.1 (0.6 to 3.6)
Diastolic blood pressure (Week 12) (n=286, 144)	-0.8 (-1.8 to 0.2)	1.0 (-0.3 to 2.4)
Diastolic blood pressure (Week 16) (n=278, 139)	-1.1 (-2.1 to -0.1)	1.3 (-0.0 to 2.6)
Diastolic blood pressure (Week 20) (n=276, 137)	-0.7 (-1.8 to 0.4)	1.1 (-0.3 to 2.5)
Diastolic blood pressure (Week 24) (n=273, 134)	-1.7 (-2.8 to -0.6)	0.5 (-0.9 to 1.9)
Diastolic blood pressure (Week 28) (n=264, 132)	-1.6 (-2.7 to -0.5)	0.2 (-1.3 to 1.7)
Diastolic blood pressure (Week 36) (n=261, 129)	-1.2 (-2.4 to 0.1)	0.2 (-1.1 to 1.6)
Diastolic blood pressure (Week 44) (n=250, 125)	-0.3 (-1.5 to 1.0)	0.4 (-1.0 to 1.8)
Diastolic blood pressure (Week 52) (n=246, 125)	-0.5 (-1.7 to 0.7)	0.1 (-1.4 to 1.6)

No statistical analysis provided for Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings

11. Other Pre-specified Outcome Measure: Mean Changes From Baseline in Heart Rate [ Time Frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52 ]

Measure Type	Other Pre-specified
Measure Name	Mean Changes From Baseline in Heart Rate
Measure Description
Time Frame	Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 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.
All participants who received at least 1 dose of double-blind study medication.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	304	151
Mean Changes From Baseline in Heart Rate [units: Beats per minute] Number (95% Confidence Interval)
Week 2 (n=294, 147)	-0.5 (-1.4 to 0.4)	-0.7 (-1.8 to 0.4)
Week 4 (n=293, 144)	-0.5 (-1.5 to 0.5)	-1.0 (-2.1 to 0.2)
Week 6 (n=280, 141)	-0.5 (-1.5 to 0.4)	-0.9 (-2.3 to 0.4)
Week 8 (n=290, 142)	-0.0 (-1.0 to 1.0)	-0.7 (-2.0 to 0.6)
Week 12 (n=286, 144)	0.3 (-0.7 to 1.3)	0.2 (-1.0 to 1.4)
Week 16 (n=278, 139)	-1.0 (-2.1 to 0.1)	-0.6 (-2.1 to 1.0)
Week 20 (n=276, 137)	-0.5 (-1.6 to 0.6)	0.4 (-0.9 to 1.8)
Week 24 (n=273, 134)	0.0 (-1.2 to 1.3)	-1.0 (-2.5 to 0.4)
Week 28 (n=264, 132)	-1.0 (-2.1 to 0.2)	-0.6 (-2.1 to 0.9)
Week 36 (n=261, 129)	0.0 (-1.1 to 1.2)	-0.0 (-1.4 to 1.4)
Week 44 (n=250, 125)	0.2 (-0.9 to 1.4)	-0.7 (-2.3 to 1.0)
Week 52 (n=246, 125)	-0.3 (-1.5 to 0.8)	0.2 (-1.7 to 2.1)

No statistical analysis provided for Mean Changes From Baseline in Heart Rate

12. Other Pre-specified Outcome Measure: Shift in Platelet Counts From Baseline to Selected Visits (LOCF) [ Time Frame: Baseline and Weeks 24 and 52 ]

Measure Type	Other Pre-specified
Measure Name	Shift in Platelet Counts From Baseline to Selected Visits (LOCF)
Measure Description	Platelet count=value*10^9 c/L
Time Frame	Baseline and Weeks 24 and 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.
All participants who received at least 1 dose of double-blind study medication.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	304	151
Shift in Platelet Counts From Baseline to Selected Visits (LOCF) [units: Participants]
Baseline <= 100; Week 24 <= 100	0	0
Baseline <= 100; Week 24 >100 - <= 600	0	0
Baseline <= 100; Week 24 >600	0	0
Baseline >100 - <= 600; Week 24 <= 100	1	1
Baseline >100 - <= 600; Week 24 >100 - <= 600	296	143
Baseline >100 - <= 600; Week 24 >600	0	0
Baseline >600; Week 24 <= 100	0	0
Baseline >600; Week 24 >100 - <= 600	0	0
Baseline >600; Week 24 >600	0	0
Baseline <= 100; Week 52 <= 100	0	0
Baseline <= 100; Week 52 >100 - <= 600	0	1
Baseline <= 100; Week 52 >600	0	0
Baseline >100 - <= 600; Week 52 <= 100	2	0
Baseline >100 - <= 600; Week 52 >100 - <= 600	295	144
Baseline >100 - <= 600; Week 52 >600	0	0
Baseline >600; Week 52 <= 100	0	0
Baseline >600; Week 52 >100 - <= 600	0	0
Baseline >600; Week 52 >600	0	0

No statistical analysis provided for Shift in Platelet Counts From Baseline to Selected Visits (LOCF)

13. Other Pre-specified Outcome Measure: Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period [ Time Frame: Baseline and during and up to 14 days after last dose of study drug (in Week 52) ]

Measure Type	Other Pre-specified
Measure Name	Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period
Measure Description	Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment. Criteria 1: if prx=0 use >=2, if prx=0.5 or 1 use >=3, if prx=2 use 4.
Time Frame	Baseline and during and up to 14 days after last dose of study drug (in 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.
All participants who received at least 1 dose of double-blind study medication.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	304	151
Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period [units: Participants]
Hemoglobin <8 g/dL (n=300; 150)	2	0
*Hematocrit <0.75prx (n=300; 150)**	2	2
*Platelets <5010^9 c/L (n=297; 145)**	0	0
*Platelets >1.5ULN (n=297; 145)**	0	0
*Leukocytes <21000 c/uL (n=300; 150)**	0	1
*Neutrophils <11000 c/uL (n=296; 150)**	1	0
*Eosinophils >0.91000 c/uL (n=296; 150)**	9	7
*Lymphocytes <=0.751000 c/uL (n=296; 150)**	3	2
*Alkaline phosphatase >3prx & >ULN (n=302; 150)**	2	1
Alkaline phosphatase >1.5 ULN (n=302; 150)	10	5
*Aspartate aminotransferase >3 ULN (n=298; 148)**	2	0
*Aspartate aminotransferase>5 ULN (n=298; 148)**	1	0
*Aspartate aminotransferase >10ULN (n=298; 148)**	0	0
*Aspartate aminotransferase >20ULN (n=298; 148)**	0	0
*Alanine transaminase >3ULN (n=300; 148)**	5	3
*Alanine transaminase >5ULN (n=300; 148)**	1	0
*Alanine transaminase >10ULN (n=300; 148)**	0	0
*Alanine transaminase >20ULN (n=300; 148)**	0	0
Bilirubin, total >2 mg/dL (n=301; 150)	0	0
*Bilirubin, total >1.5ULN (n=301; 150)**	0	1
*Bilirubin, total >2ULN (n=301; 150)**	0	0
*Blood urea nitrogen >2prx & >ULN (n=302; 150)**	5	7
Creatinine >2.5 mg/dL (n=303; 150)	0	0
Glucose, serum fasting <50 mg/dL (n=0; 0)	0	0
Glucose, serum fasting >500 mg/dL (n=0; 0)	0	0
Glucose, serum unspecified <50 mg/dL (n=0; 0)	0	0
Glucose, serum unspecified >500 mg/dL (n=0; 0)	0	0
Glucose, plasma fasting <50 mg/dL (n=301;150)	5	0
Glucose, plasma fasting >500 mg/dL (n=301;150)	0	1
Glucose, plasma unspecified <50 mg/dL (n=272; 133)	5	1
Glucose, plasma unspecified >500 mg/d (n=272; 133)	1	1
*Sodium, serum <0.9prx & <=130 mEq/L (n=302; 150)**	1	0
*Sodium, serum >1.1prx & >=150 mEq/L (n=302; 150)**	0	0
Potassium, serum <0.8 prx &<=3.2 mEq/L(n=300; 148)	3	1
*Potassium, serum >1.2prx&>= 6.0 mEq/L(n=300; 148)**	8	8
Chloride, serum <90 mEq/L (n=302; 150)	1	0
Chloride, serum >120 mEq/L (n=302; 150)	0	0
*Albumin <0.9LLN; if prx<LLN, 0.75prx (n=302,150)*	1	0
*Creatine kinase >5ULN (n=301, 148)**	6	2
*Uric acid >1.5ULN; if prx >ULN, >2 (n=0,0)**	0	0
Protein urine (see criteria 1) (n=297,146)	8	3
Blood urine (see criteria 1) (n=297; 146)	14	2
Red blood cells urine (see criteria 1) (n=53; 31)	8	3
White blood cells urine (see criteria 1)(n=115;53)	35	10

No statistical analysis provided for Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period

14. Other Pre-specified Outcome Measure: Percentage of Participants With Reported and Confirmed Hypoglycemia [ Time Frame: Baseline to Week 52 ]

Measure Type	Other Pre-specified
Measure Name	Percentage of Participants With Reported and Confirmed Hypoglycemia
Measure Description	Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/
Time Frame	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.

Reporting Groups

	Description
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes

Measured Values

	Saxagliptin, 5 mg + insulin	Placebo + insulin
Number of Participants Analyzed [units:participants]	300	149
Percentage of Participants With Reported and Confirmed Hypoglycemia [units: Percentage of Participants]
Reported	19.4	24.5
Confirmed	7.6	6.6

No statistical analysis provided for Percentage of Participants With Reported and Confirmed Hypoglycemia

Serious Adverse Events

Time Frame	Baseline to Week 52
Additional Description	No text entered.

Reporting Groups

	Description
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes

Serious Adverse Events

Placebo + insulin

Saxagliptin, 5 mg + insulin

Total, serious adverse events

# participants affected / at risk

13/151 (8.61%)

25/304 (8.22%)

EYE DISORDERS

DIABETIC RETINOPATHY¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

INVESTIGATIONS

LIVER FUNCTION TEST ABNORMAL¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

CARDIAC DISORDERS

ANGINA PECTORIS¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

CARDIAC DISORDERS

CARDIAC FAILURE¹,^†

# participants affected / at risk

0/151 (0.00%)

2/304 (0.66%)

CARDIAC DISORDERS

MYOCARDIAL ISCHAEMIA¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

CARDIAC DISORDERS

MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

CARDIAC DISORDERS

ACUTE CORONARY SYNDROME¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

CARDIAC DISORDERS

CORONARY ARTERY OCCLUSION¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

CARDIAC DISORDERS

ACUTE MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

VASCULAR DISORDERS

HYPERTENSION¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

VASCULAR DISORDERS

PERIPHERAL ISCHAEMIA¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

VASCULAR DISORDERS

PERIPHERAL VASCULAR DISORDER¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

VASCULAR DISORDERS

THROMBOPHLEBITIS SUPERFICIAL¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

HEPATOBILIARY DISORDERS

JAUNDICE¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

HEPATOBILIARY DISORDERS

CHOLANGITIS¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

HEPATOBILIARY DISORDERS

CHOLANGITIS ACUTE¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

NERVOUS SYSTEM DISORDERS

SCIATICA¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

NERVOUS SYSTEM DISORDERS

THALAMIC INFARCTION¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

NERVOUS SYSTEM DISORDERS

TRANSIENT ISCHAEMIC ATTACK¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

GASTROINTESTINAL DISORDERS

CONSTIPATION¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

GASTROINTESTINAL DISORDERS

CROHN'S DISEASE¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

GASTROINTESTINAL DISORDERS

PANCREATITIS CHRONIC¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

INFECTIONS AND INFESTATIONS

PNEUMONIA¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

INFECTIONS AND INFESTATIONS

BRONCHITIS¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

INFECTIONS AND INFESTATIONS

CELLULITIS¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

INFECTIONS AND INFESTATIONS

ABSCESS LIMB¹,^†

# participants affected / at risk

2/151 (1.32%)

0/304 (0.00%)

INFECTIONS AND INFESTATIONS

DENGUE FEVER¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

INFECTIONS AND INFESTATIONS

OSTEOMYELITIS¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

INFECTIONS AND INFESTATIONS

DIVERTICULITIS¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

INFECTIONS AND INFESTATIONS

ARTHRITIS INFECTIVE¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

INFECTIONS AND INFESTATIONS

INTESTINAL GANGRENE¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

INFECTIONS AND INFESTATIONS

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

RENAL AND URINARY DISORDERS

RENAL IMPAIRMENT¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

RENAL AND URINARY DISORDERS

RENAL FAILURE ACUTE¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

METABOLISM AND NUTRITION DISORDERS

HYPOGLYCAEMIA¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

IRON DEFICIENCY ANAEMIA¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

ANAEMIA VITAMIN B12 DEFICIENCY¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

CONTUSION¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

ANKLE FRACTURE¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

NECK PAIN¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

ARTHRALGIA¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

OSTEOPOROSIS¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

OSTEOARTHRITIS¹,^†

# participants affected / at risk

0/151 (0.00%)

2/304 (0.66%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

PAIN IN EXTREMITY¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

INTERVERTEBRAL DISC PROTRUSION¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

CHEST PAIN¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

INFLUENZA LIKE ILLNESS¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

BREAST CANCER¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

PITUITARY TUMOUR¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

UTERINE LEIOMYOMA¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

PANCREATIC CARCINOMA¹,^†

# participants affected / at risk

0/151 (0.00%)

1/304 (0.33%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

PROSTATE CANCER METASTATIC¹,^†

# participants affected / at risk

1/151 (0.66%)

0/304 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	Baseline to Week 52
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Placebo + insulin	Placebo added to ongoing insulin with metformin therapy for up to 24 weeks in patients with type 2 diabetes
Saxagliptin, 5 mg + insulin	Saxagliptin, 5 mg, added to ongoing insulin with or without metformin therapy for up to 24 weeks in patients with type 2 diabetes

Other Adverse Events

Placebo + insulin

Saxagliptin, 5 mg + insulin

Total, other (not including serious) adverse events

# participants affected / at risk

64/151 (42.38%)

96/304 (31.58%)

VASCULAR DISORDERS

HYPERTENSION¹,^†

# participants affected / at risk

8/151 (5.30%)

8/304 (2.63%)

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

6/151 (3.97%)

18/304 (5.92%)

INFECTIONS AND INFESTATIONS

INFLUENZA¹,^†

# participants affected / at risk

14/151 (9.27%)

10/304 (3.29%)

INFECTIONS AND INFESTATIONS

BRONCHITIS¹,^†

# participants affected / at risk

4/151 (2.65%)

16/304 (5.26%)

INFECTIONS AND INFESTATIONS

PHARYNGITIS¹,^†

# participants affected / at risk

8/151 (5.30%)

11/304 (3.62%)

INFECTIONS AND INFESTATIONS

NASOPHARYNGITIS¹,^†

# participants affected / at risk

10/151 (6.62%)

19/304 (6.25%)

INFECTIONS AND INFESTATIONS

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

12/151 (7.95%)

23/304 (7.57%)

INFECTIONS AND INFESTATIONS

UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

11/151 (7.28%)

19/304 (6.25%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

PAIN IN EXTREMITY¹,^†

# participants affected / at risk

10/151 (6.62%)

7/304 (2.30%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

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: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication

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:	Boaz Hirschberg
Organization:	AstraZeneca Pharmaceuticals
E-mail:	[email protected]

Documents available

BMS Clinical Trials Disclosure
Download
Investigator Inquiry form
Download
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
Download
Pharma web posting
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Bristol-Myers Squibb

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Local Institution

Local Institution

Danny W. Jackson P.A.

Panhandle Family Care Assoc. & Coastal Palms Res. Grp Inc.

Ritchken & First M.D.'S

Aurora Advanced Healthcare

Local Institution

Local Institution

BMS Clinical Trials Disclosure

Investigator Inquiry form

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Pharma web posting

Trial Results Summaries