A Phase 3 Study of BMS-477118 in combination with metformin in subjects with type 2 diabetes who are not controlled with diet and exercise

Study identifier:CV181-039

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicenter, Randomized, Double-Blind Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination with Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects with Type 2 Diabetes Who Have Inadequate Glycemic Control

Medical condition

diabetes

Phase

Phase 3

Healthy volunteers

Study drug

Saxagliptin, Metformin, Placebo, pioglitazone

Sex

All

Actual Enrollment

1306

Study type

Interventional

Age

18 Years - 77 Years

Date

Study Start Date: 01 May 2006

Primary Completion Date: 01 Nov 2007

Study Completion Date: 01 Dec 2008

Study design

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

Verification:

Verified 01 Mar 2015 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Diabetes Center Of The Southwest

Midland, TX, United States, 79705

Location

Hill Country Medical Associates

New Braunfels, TX, United States, 78130

Location

Physicians Research Group

Indianapolis, IN, United States, 46250

Location

Cedar Crosse Research Center

Chicago, IL, United States, 60607

Location

Your Diabetes Endocrine Nutrition Group

Mentor, OH, United States, 44060

Location

Coastal Biomedical Research Inc

Santa Monica, CA, United States, 90404

Location

Middle Tennessee Clinical Research

Fayetteville, TN, United States, 37334

Location

Internal Medicine Of Greer

Greer, SC, United States, 29651

Arms	Assigned Interventions
Experimental: Saxagliptin and Metformin (A) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Saxagliptin Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: Metformin Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 mg, as needed (12 months LT)
Experimental: Saxagliptin and Metformin (B) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Saxagliptin Coated tablets, PO, 5 mg, Daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: Metformin Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 mg, as needed (12 months LT)
Experimental: Saxagliptin and Placebo (C) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Saxagliptin Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: Placebo Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 mg, as needed (12 months LT)
Active Comparator: Metformin and Placebo (D) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Metformin Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT) Drug: Placebo Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 mg, as needed (12 months LT)

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
No text entered.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin Immediate Release (IR) was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Participant Flow: Overall Study

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg	Metformin
STARTED	320	323	335	328
Completed study without being rescued	179	177	113	144
COMPLETED	229	231	209	219
NOT COMPLETED	91	92	126	109
Lack of Efficacy	18	18	35	29
Withdrawal of Consent by Subject	20	24	28	25
Lost to Follow-up	22	23	29	22
Adverse Event	14	10	14	14
Subject no longer meets study criteria	4	2	8	7
Poor/Noncompliance	11	8	4	5
Physician Decision	0	1	3	2
Death	1	2	2	3
Pregnancy	0	2	1	1
Administrative Reason by Sponsor	1	2	2	1

Baseline Characteristics

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

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin Immediate Release (IR) was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Baseline Measures

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg	Metformin	Total
Number of Participants [units: Participants]	320	323	335	328	1306
Age Continuous [units: years] Mean ± Standard Deviation	51.95 ± 10.43	52.08 ± 11.59	52.09 ± 10.17	51.83 ± 10.74	51.99 ± 10.73
Gender, Male/Female [units: participants]
Female	155	177	166	165	663
Male	165	146	169	163	643

Outcome Measures

1. Primary Outcome Measure: Change From Baseline in Hemoglobin A1c (A1C) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [ Time Frame: Baseline, Week 24 ]

Measure Type	Primary
Measure Name	Change From Baseline in Hemoglobin A1c (A1C) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy
Measure Description	Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Time Frame	Baseline, 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 took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 Last Observation Carried Forward (LOCF), subjects must have had a baseline and at least 1 post-baseline measurement. If participant received rescue medication, that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg
Number of Participants Analyzed [units:participants]	306	315	317
Change From Baseline in Hemoglobin A1c (A1C) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [units: percent] Mean (Standard Error)
Baseline Mean	9.41 (0.072)	9.53 (0.069)	9.61 (0.075)
Week 24 Mean	6.93 (0.066)	7.02 (0.067)	7.86 (0.085)
Adjusted Mean Change from Baseline	-2.53 (0.070)	-2.49 (0.069)	-1.69 (0.069)

No statistical analysis provided for Change From Baseline in Hemoglobin A1c (A1C) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy

2. Primary Outcome Measure: Change From Baseline in A1C at Week 24, saxagliptin plus metformin versus metformin monotherapy [ Time Frame: Baseline, Week 24 ]

Measure Type	Primary
Measure Name	Change From Baseline in A1C at Week 24, saxagliptin plus metformin versus metformin monotherapy
Measure Description	Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Time Frame	Baseline, 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 took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Metformin
Number of Participants Analyzed [units:participants]	306	315	313
Change From Baseline in A1C at Week 24, saxagliptin plus metformin versus metformin monotherapy [units: percent] Mean (Standard Error)
Baseline Mean	9.41 (0.072)	9.53 (0.069)	9.43 (0.073)
Week 24 Mean	6.93 (0.066)	7.02 (0.067)	7.48 (0.084)
Adjusted Mean Change from Baseline	-2.53 (0.070)	-2.49 (0.069)	-1.99 (0.069)

No statistical analysis provided for Change From Baseline in A1C at Week 24, saxagliptin plus metformin versus metformin monotherapy

3. Secondary Outcome Measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [ Time Frame: Baseline, Week 24 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy
Measure Description	Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Time Frame	Baseline, 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 took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg
Number of Participants Analyzed [units:participants]	315	317	327
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [units: mg/dL] Mean (Standard Error)
Baseline Mean	198.9 (3.17)	204.3 (3.35)	200.9 (3.03)
Week 24 Mean	140.2 (2.39)	140.1 (2.34)	169.9 (3.20)
Adjusted Mean Change from Baseline	-59.8 (2.34)	-62.2 (2.34)	-30.9 (2.30)

No statistical analysis provided for Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy

4. Secondary Outcome Measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus metformin monotherapy [ Time Frame: Baseline, Week 24 ]

Measure Type	Secondary
Measure Name	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus metformin monotherapy
Measure Description	Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Time Frame	Baseline, 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 took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Metformin
Number of Participants Analyzed [units:participants]	315	317	320
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus metformin monotherapy [units: mg/dL] Mean (Standard Error)
Baseline Mean	198.9 (3.17)	204.3 (3.35)	199.1 (3.28)
Week 24 Mean	140.2 (2.39)	140.1 (2.34)	152.7 (2.80)
Adjusted Mean Change from Baseline	-59.8 (2.34)	-62.2 (2.34)	-47.3 (2.33)

No statistical analysis provided for Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, saxagliptin plus metformin versus metformin monotherapy

5. Secondary Outcome Measure: Percentage of Participants Achieving A1C < 7% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving A1C < 7% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy
Measure Description	Percentage of participants achieving A1C < 7%, the American Diabetes Association’s defined goal for glycemia, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.
Time Frame	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 took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg
Number of Participants Analyzed [units:participants]	307	315	320
Percentage of Participants Achieving A1C < 7% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [units: Percentage of participants]	60.3	59.7	32.2

No statistical analysis provided for Percentage of Participants Achieving A1C < 7% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy

6. Secondary Outcome Measure: Percentage of Participants achieving A1C < 7% at Week 24, saxagliptin plus metformin versus metformin monotherapy [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants achieving A1C < 7% at Week 24, saxagliptin plus metformin versus metformin monotherapy
Measure Description	Percentage of participants achieving A1C < 7%, the American Diabetes Association’s defined goal for glycemia, at each dose of saxagliptin plus metformin versus metformin alone at Week 24.
Time Frame	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 took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Metformin
Number of Participants Analyzed [units:participants]	307	315	314
Percentage of Participants achieving A1C < 7% at Week 24, saxagliptin plus metformin versus metformin monotherapy [units: Percentage of participants]	60.3	59.7	41.1

No statistical analysis provided for Percentage of Participants achieving A1C < 7% at Week 24, saxagliptin plus metformin versus metformin monotherapy

7. Secondary Outcome Measure: Changes from baseline in postprandial glucose (PPG) area under the curve (AUC) response to an oral glucose tolerance test (OGTT) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [ Time Frame: Baseline, Week 24 ]

Measure Type	Secondary
Measure Name	Changes from baseline in postprandial glucose (PPG) area under the curve (AUC) response to an oral glucose tolerance test (OGTT) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy
Measure Description	Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline value.
Time Frame	Baseline, 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 took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg
Number of Participants Analyzed [units:participants]	142	131	145
Changes from baseline in postprandial glucose (PPG) area under the curve (AUC) response to an oral glucose tolerance test (OGTT) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [units: mg*min/dL] Mean (Standard Error)
Baseline Mean	55531 (1116.5)	57219 (1169.6)	57584 (1143.4)
Week 24 Mean	35324 (890.0)	35790 (888.9)	41229 (1050.9)
Adjusted Mean Change from Baseline	-21080 (836.5)	-21336 (869.6)	-16054 (826.7)

No statistical analysis provided for Changes from baseline in postprandial glucose (PPG) area under the curve (AUC) response to an oral glucose tolerance test (OGTT) at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy

8. Secondary Outcome Measure: Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, saxagliptin plus metformin versus Metformin monotherapy [ Time Frame: Baseline, Week 24 ]

Measure Type	Secondary
Measure Name	Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, saxagliptin plus metformin versus Metformin monotherapy
Measure Description	Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjsuted for baseline value.
Time Frame	Baseline, 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 took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Metformin
Number of Participants Analyzed [units:participants]	142	131	135
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, saxagliptin plus metformin versus Metformin monotherapy [units: mg*min/dL] Mean (Standard Error)
Baseline Mean	55531 (1116.5)	57219 (1169.6)	57937 (1281.7)
Week 24 Mean	35324 (890.0)	35790 (888.9)	42428 (1082.1)
Adjusted Mean Change from Baseline	-21080 (836.5)	-21336 (869.6)	-15005 (857.0)

No statistical analysis provided for Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, saxagliptin plus metformin versus Metformin monotherapy

9. Secondary Outcome Measure: Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy
Measure Description	Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.
Time Frame	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 took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg
Number of Participants Analyzed [units:participants]	307	315	320
Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [units: Percentage of Participants]	45.3	40.6	20.3

No statistical analysis provided for Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy

10. Secondary Outcome Measure: Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus metformin monotherapy [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus metformin monotherapy
Measure Description	Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus metformin alone at Week 24.
Time Frame	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 took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, participants must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Metformin
Number of Participants Analyzed [units:participants]	307	315	314
Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus metformin monotherapy [units: Percentage of participants]	45.3	40.6	29.0

No statistical analysis provided for Percentage of Participants Achieving A1C ≤6.5% at Week 24, saxagliptin plus metformin versus metformin monotherapy

11. Secondary Outcome Measure: Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy
Measure Description	Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus saxagliptin alone.
Time Frame	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 took at least 1 dose of double-blind treatment were included in the Week 24 LOCF analysis.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Saxagliptin 10 mg
Number of Participants Analyzed [units:participants]	320	323	335
Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy [units: Percentage of participants]	7.5	5.9	21.2

No statistical analysis provided for Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus saxagliptin monotherapy

12. Secondary Outcome Measure: Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus metformin monotherapy [ Time Frame: Week 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus metformin monotherapy
Measure Description	Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus metformin alone.
Time Frame	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 took at least 1 dose of double-blind treatment were included in the Week 24 LOCF analysis.

Reporting Groups

	Description
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.

Measured Values

	Saxagliptin 5 mg + Metformin	Saxagliptin 10 mg + Metformin	Metformin
Number of Participants Analyzed [units:participants]	320	323	328
Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus metformin monotherapy [units: Percentage of participants]	7.5	5.9	10.1

No statistical analysis provided for Percentage of Participants Requiring Rescue or Discontinuation at Week 24, saxagliptin plus metformin versus metformin monotherapy

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.

Serious Adverse Events

Metformin

Saxagliptin 10 mg

Saxagliptin 10 mg + Metformin

Saxagliptin 5 mg + Metformin

Total, serious adverse events

# participants affected / at risk

15/328 (4.57%)

16/335 (4.78%)

22/323 (6.81%)

16/320 (5.00%)

EYE DISORDERS

DIABETIC RETINOPATHY¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

CARDIAC DISORDERS

CARDIAC ARREST¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

CARDIAC DISORDERS

CARDIAC FAILURE¹,^†

# participants affected / at risk

2/328 (0.61%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

CARDIAC DISORDERS

ATRIAL FIBRILLATION¹,^†

# participants affected / at risk

2/328 (0.61%)

0/335 (0.00%)

1/323 (0.31%)

1/320 (0.31%)

CARDIAC DISORDERS

CARDIAC FAILURE ACUTE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

CARDIAC DISORDERS

MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

2/323 (0.62%)

0/320 (0.00%)

CARDIAC DISORDERS

CORONARY ARTERY DISEASE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

CARDIAC DISORDERS

ACUTE MYOCARDIAL INFARCTION¹,^†

# participants affected / at risk

2/328 (0.61%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

CARDIAC DISORDERS

ARTERIOSCLEROSIS CORONARY ARTERY¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

CARDIAC DISORDERS

ATRIOVENTRICULAR BLOCK SECOND DEGREE¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

VASCULAR DISORDERS

EXTREMITY NECROSIS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

VASCULAR DISORDERS

DIABETIC MACROANGIOPATHY¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

HEPATOBILIARY DISORDERS

CHOLECYSTITIS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

HEPATOBILIARY DISORDERS

CHOLELITHIASIS¹,^†

# participants affected / at risk

1/328 (0.30%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

HEPATOBILIARY DISORDERS

CHOLECYSTITIS ACUTE¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

NERVOUS SYSTEM DISORDERS

SCIATICA¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

NERVOUS SYSTEM DISORDERS

ISCHAEMIC STROKE¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

NERVOUS SYSTEM DISORDERS

SYNCOPE VASOVAGAL¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

NERVOUS SYSTEM DISORDERS

CEREBRAL INFARCTION¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

NERVOUS SYSTEM DISORDERS

HAEMORRHAGIC STROKE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

NERVOUS SYSTEM DISORDERS

FACIAL NERVE DISORDER¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

NERVOUS SYSTEM DISORDERS

CEREBROVASCULAR ACCIDENT¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

NERVOUS SYSTEM DISORDERS

TRANSIENT ISCHAEMIC ATTACK¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

GASTROINTESTINAL DISORDERS

GASTRITIS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

1/320 (0.31%)

GASTROINTESTINAL DISORDERS

PANCREATITIS¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

GASTROINTESTINAL DISORDERS

HIATUS HERNIA¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

GASTROINTESTINAL DISORDERS

FOOD POISONING¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

GASTROINTESTINAL DISORDERS

GASTRIC POLYPS¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

GASTROINTESTINAL DISORDERS

INGUINAL HERNIA¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

GASTROINTESTINAL DISORDERS

UMBILICAL HERNIA¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

GASTROINTESTINAL DISORDERS

GASTRITIS EROSIVE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

GASTROINTESTINAL DISORDERS

PANCREATITIS ACUTE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

EAR AND LABYRINTH DISORDERS

DEAFNESS¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

INFECTIONS AND INFESTATIONS

SEPSIS¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

INFECTIONS AND INFESTATIONS

TETANUS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

INFECTIONS AND INFESTATIONS

PNEUMONIA¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

INFECTIONS AND INFESTATIONS

ERYSIPELAS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

INFECTIONS AND INFESTATIONS

APPENDICITIS¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

INFECTIONS AND INFESTATIONS

GASTROENTERITIS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

INFECTIONS AND INFESTATIONS

SCROTAL ABSCESS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

INFECTIONS AND INFESTATIONS

PHARYNGOTONSILLITIS¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

RENAL AND URINARY DISORDERS

NEPHROLITHIASIS¹,^†

# participants affected / at risk

1/328 (0.30%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

RENAL AND URINARY DISORDERS

RENAL FAILURE ACUTE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

METABOLISM AND NUTRITION DISORDERS

DEHYDRATION¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

METABOLISM AND NUTRITION DISORDERS

HYPERKALAEMIA¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

METABOLISM AND NUTRITION DISORDERS

DIABETES MELLITUS¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

LYMPHOPENIA¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

LYMPHADENITIS¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

ROSACEA¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

INGROWING NAIL¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

DERMATITIS ALLERGIC¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

MENOMETRORRHAGIA¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

ACQUIRED PHIMOSIS¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

UTERINE HAEMORRHAGE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

ACCIDENT¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

OVERDOSE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

1/320 (0.31%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

WRIST FRACTURE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

LOWER LIMB FRACTURE¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

UPPER LIMB FRACTURE¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

ROAD TRAFFIC ACCIDENT¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

BACK PAIN¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

OSTEOARTHRITIS¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

OSTEOCHONDROSIS¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

LUNG CONSOLIDATION¹,^†

# participants affected / at risk

0/328 (0.00%)

1/335 (0.30%)

0/323 (0.00%)

0/320 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

PYREXIA¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

SUDDEN DEATH¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

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

PAPILLOMA¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

1/323 (0.31%)

0/320 (0.00%)

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

BILE DUCT CANCER¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

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

PANCREATIC NEOPLASM¹,^†

# participants affected / at risk

1/328 (0.30%)

0/335 (0.00%)

0/323 (0.00%)

0/320 (0.00%)

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

LYMPHOPROLIFERATIVE DISORDER¹,^†

# participants affected / at risk

0/328 (0.00%)

0/335 (0.00%)

0/323 (0.00%)

1/320 (0.31%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Metformin	The Metformin group includes data from participants randomized to receive coadministration of metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose and placebo resembling saxagliptin.
Saxagliptin 10 mg	The Saxagliptin 10 mg group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and placebo resembling metformin.
Saxagliptin 10 mg + Metformin	The Saxagliptin 10 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 10 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.
Saxagliptin 5 mg + Metformin	The Saxagliptin 5 mg + Metformin group includes data from participants randomized to receive coadministration of blinded, fixed-dose saxagliptin 5 mg oral tablets and metformin IR 500 mg. Metformin IR was titrated, as tolerated, in increments of 500 mg up to a maximum of 2000 mg daily dose.

Other Adverse Events

Metformin

Saxagliptin 10 mg

Saxagliptin 10 mg + Metformin

Saxagliptin 5 mg + Metformin

Total, other (not including serious) adverse events

# participants affected / at risk

106/328 (32.32%)

106/335 (31.64%)

122/323 (37.77%)

116/320 (36.25%)

VASCULAR DISORDERS

HYPERTENSION¹,^†

# participants affected / at risk

17/328 (5.18%)

19/335 (5.67%)

21/323 (6.50%)

27/320 (8.44%)

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

18/328 (5.49%)

31/335 (9.25%)

36/323 (11.15%)

31/320 (9.69%)

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

30/328 (9.15%)

12/335 (3.58%)

41/323 (12.69%)

26/320 (8.13%)

INFECTIONS AND INFESTATIONS

INFLUENZA¹,^†

# participants affected / at risk

19/328 (5.79%)

17/335 (5.07%)

13/323 (4.02%)

20/320 (6.25%)

INFECTIONS AND INFESTATIONS

NASOPHARYNGITIS¹,^†

# participants affected / at risk

19/328 (5.79%)

24/335 (7.16%)

19/323 (5.88%)

29/320 (9.06%)

INFECTIONS AND INFESTATIONS

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

25/328 (7.62%)

23/335 (6.87%)

22/323 (6.81%)

13/320 (4.06%)

INFECTIONS AND INFESTATIONS

UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

10/328 (3.05%)

14/335 (4.18%)

19/323 (5.88%)

15/320 (4.69%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.1
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
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Results Point of Contact

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

Documents available

BMS Clinical Trials Disclosure
Download
For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm
Download
PhRMA website-CSR Synopsis
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

Diabetes Center Of The Southwest

Hill Country Medical Associates

Physicians Research Group

Cedar Crosse Research Center

Your Diabetes Endocrine Nutrition Group

Coastal Biomedical Research Inc

Middle Tennessee Clinical Research

Internal Medicine Of Greer

BMS Clinical Trials Disclosure

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

PhRMA website-CSR Synopsis

Trial Results Summaries