A Study Comparing Exenatide With Basal Insulin in Achieving a Target HbA1c With Minimum Weight Gain in Type 2 Diabetes Patients

Study identifier:H8O-BP-GWBG

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

An Open Label Study Comparing Exenatide with Basal Insulin in Achieving an HbA1c of ≤ 7.4% with Minimum Weight Gain, in Type 2 Diabetes Patients who are not Achieving Adequate HbA1c Control on Oral Anti Diabetic Therapies Alone

Medical condition

Type 2 Diabetes

Phase

Phase 3

Healthy volunteers

Study drug

exenatide, insulin glargine

Sex

All

Actual Enrollment

235

Study type

Interventional

Age

30 Years +

Date

Study Start Date: 01 Jun 2006

Primary Completion Date: 01 Apr 2008

Study Completion Date: 01 Apr 2008

Study design

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

Verification:

Verified 01 Mar 2015 by AstraZeneca Pharmaceuticals

Collaborators

Eli Lilly and Company

Inclusion and exclusion criteria

Location

Research Site

London, United Kingdom

Location

Research Site

Torquay, United Kingdom

Location

Research Site

Wakefield, United Kingdom

Location

Research Site

Swansea, United Kingdom

Location

Research Site

Oldham, United Kingdom

Location

Research Site

Nottingham, United Kingdom

Location

Research Site

High Wycombe, United Kingdom

Location

Research Site

Liverpool, United Kingdom

Arms	Assigned Interventions
Experimental: 1	Drug: exenatide subcutaneous injection, 5mcg or 10mcg, twice a day Other Name: Byetta
Active Comparator: 2	Drug: insulin glargine subcutaneous injection, titrated to target blood glucose level, once a day Other Name: Lantus

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at 35 study centers in the United Kingdom. Recruitment occurred from June 2006 to October 2007.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One patient assigned to the Insulin Glargine group withdrew from the study prior to receiving study drug. This patient is not included in the analysis set.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Participant Flow: Overall Study

	Exenatide	Insulin Glargine
STARTED	118	117
Full Analysis Set (FAS)	118^[1]	116^[2]
COMPLETED	99	104
NOT COMPLETED	19	13
Adverse Event	7	4
Protocol Violation	1	1
Physician Decision	2	3
Lack of Efficacy	0	1
Entry criterion not met	1	2
Subject decision	8	2

[1]	FAS = received ≥ 1 dose of study drug
[2]	FAS = received ≥ 1 dose of study drug

Baseline Characteristics

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

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Baseline Measures

	Exenatide	Insulin Glargine	Total
Number of Participants [units: Participants]	118	116	234.0
Age Continuous [units: years] Mean ± Standard Deviation	56.8 ± 10.2	56.2 ± 7.9	56.5 ± 9.1
Gender, Male/Female [units: participants]
Female	35	39	74
Male	83	77	160
Region of Enrollment [units: participants] United Kingdom	118	116	234
Types of oral antidiabetic medication combinations administered at baseline [units: participants]
metformin and sulfonylurea	50	49	99
metformin and thiazolidinedione	17	15	32
sulfonylurea and thiazolidinedione	2	4	6
metformin, sulfonylurea, and thiazolidinedione	48	47	95
other	1	1	2
Baseline apolipoprotein-B [units: g/L] Mean ± Standard Deviation	0.84 ± 0.24	0.88 ± 0.24	0.86 ± 0.24
Baseline fasting serum glucose [units: mmol/L] Mean ± Standard Deviation	10.84 ± 2.23	10.12 ± 2.22	10.48 ± 2.25
Baseline fasting serum total cholesterol (TC) [units: mmol/L] Mean ± Standard Deviation	4.45 ± 1.05	4.63 ± 1.20	4.54 ± 1.13
Baseline fasting serum triglycerides [units: mmol/L] Mean ± Standard Deviation	1.94 ± 1.01	2.31 ± 2.24	2.13 ± 1.75
Baseline high density lipoprotein (HDL) cholesterol [units: mmol/L] Mean ± Standard Deviation	1.14 ± 0.24	1.15 ± 0.29	1.15 ± 0.27
Baseline low density lipoprotein (LDL) cholesterol [units: mmol/L] Mean ± Standard Deviation	2.38 ± 0.82	2.49 ± 1.02	2.43 ± 0.93
Baseline total cholesterol to high density lipoprotein cholesterol ratio [units: ratio] Mean ± Standard Deviation	4.00 ± 1.10	4.29 ± 2.15	4.15 ± 1.72

Outcome Measures

1. Primary Outcome Measure: Percent of patients who achieved HbA1c ≤ 7.4% with minimal weight gain (≤ 1kg) [ Time Frame: 26 weeks ]

Measure Type	Primary
Measure Name	Percent of patients who achieved HbA1c ≤ 7.4% with minimal weight gain (≤ 1kg)
Measure Description	Composite endpoint evaluating effect of treatment on glycemic control and weight
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set; The last post-baseline measurement set of both non-missing HbA1c and weight was used as endpoint value. Patients who did not have a baseline weight measurement and/or missing post-baseline measurements for HbA1c and/or weight were included in the analysis as non-responders.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Percent of patients who achieved HbA1c ≤ 7.4% with minimal weight gain (≤ 1kg) [units: percentage of participants]	53.4	19.8

Statistical Analysis 1 for Percent of patients who achieved HbA1c ≤ 7.4% with minimal weight gain (≤ 1kg)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	4.71
95% Confidence Interval	( 2.62 to 8.46 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the primary outcome divided by the odds of a patient in the insulin glargine arm achieving the primary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Percent of patients who achieved HbA1c ≤ 7.4% and weight gain ≤ 0.5kg [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percent of patients who achieved HbA1c ≤ 7.4% and weight gain ≤ 0.5kg
Measure Description	Composite endpoint evaluating effect of treatment on glycemic control and weight
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set; The last post-baseline measurement set of both non-missing HbA1c and weight was used as endpoint value. Patients who did not have a baseline weight measurement and/or missing post-baseline measurements for HbA1c and/or weight were included in the analysis as non-responders.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Percent of patients who achieved HbA1c ≤ 7.4% and weight gain ≤ 0.5kg [units: Percentage of participants]	52.5	16.4

Statistical Analysis 1 for Percent of patients who achieved HbA1c ≤ 7.4% and weight gain ≤ 0.5kg

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	5.76
95% Confidence Interval	( 3.11 to 10.64 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Change in fasting serum glucose [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in fasting serum glucose
Measure Description	Change in fasting serum glucose from baseline (week 0) to endpoint (week 26)
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	103	101
Change in fasting serum glucose [units: mmol/L] Least Squares Mean (Standard Error)	-2.12 (0.25)	-3.61 (0.25)

Statistical Analysis 1 for Change in fasting serum glucose

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.001

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

4. Secondary Outcome Measure: Percent of patients achieving HbA1c ≤ 7.4% [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percent of patients achieving HbA1c ≤ 7.4%
Measure Description	Percent of patients achieving specified HbA1c target at endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward. Patients with no post-baseline HbA1c measurement are regarded as non-responders in the analysis.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Percent of patients achieving HbA1c ≤ 7.4% [units: Percentage of participants]	54.2	61.2

Statistical Analysis 1 for Percent of patients achieving HbA1c ≤ 7.4%

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.280
Odds Ratio (OR)^[5]	0.75
95% Confidence Interval	( 0.44 to 1.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Percent of patients achieving HbA1c < 7% [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percent of patients achieving HbA1c < 7%
Measure Description	Percent of patients achieving specified HbA1c target at endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward. Patients with no post-baseline HbA1c measurement are regarded as non-responders in the analysis.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Percent of patients achieving HbA1c < 7% [units: Percentage of participants]	34.7	43.1

Statistical Analysis 1 for Percent of patients achieving HbA1c < 7%

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.191
Odds Ratio (OR)^[5]	0.70
95% Confidence Interval	( 0.42 to 1.19 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Percent of patients achieving HbA1c < 6.5% [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percent of patients achieving HbA1c < 6.5%
Measure Description	Percent of patients achieving specified HbA1c target at endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward. Patients with no post-baseline HbA1c measurement are regarded as non-responders in the analysis.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Percent of patients achieving HbA1c < 6.5% [units: Percentage of participants]	15.3	11.2

Statistical Analysis 1 for Percent of patients achieving HbA1c < 6.5%

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.363
Odds Ratio (OR)^[5]	1.43
95% Confidence Interval	( 0.66 to 3.07 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Change in 7 point self monitored blood glucose profile [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in 7 point self monitored blood glucose profile
Measure Description	Change from baseline to endpoint in self monitored blood glucose levels measured at 7 time points during the day
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Change in 7 point self monitored blood glucose profile [units: mmol/L] Mean (Standard Deviation)
Pre-breakfast: Baseline (Week 0)	9.98 (2.11)	9.88 (2.07)
Pre-breakfast: Change at endpoint (Week 26)	-2.01 (2.14)	-3.99 (2.39)
2 hrs after breakfast: Baseline (Week 0)	13.53 (3.07)	13.33 (2.87)
2 hrs after breakfast: Change at endpt (Week 26)	-5.09 (3.52)	-3.95 (3.89)
Pre-lunch: Baseline (Week 0)	9.95 (3.24)	9.54 (2.71)
Pre-lunch: Change at endpoint (Week 26)	-2.21 (3.11)	-2.59 (3.27)
2 hrs after lunch: Baseline (Week 0)	12.07 (3.27)	11.15 (2.59)
2 hrs after lunch: Change at endpoint (Week 26)	-3.20 (3.30)	-2.48 (3.17)
Pre-dinner: Baseline (Week 0)	9.95 (2.97)	9.37 (2.73)
Pre-dinner: Change at endpoint (Week 26)	-2.13 (2.89)	-1.46 (4.76)
2 hrs after dinner: Baseline (Week 0)	12.59 (3.28)	11.80 (2.62)
2 hrs after dinner: Change at endpoint (Week 26)	-4.59 (3.30)	-2.06 (3.22)
Bedtime: Baseline (Week 0)	11.63 (3.23)	11.24 (3.05)
Bedtime: Change at endpoint (Week 26)	-3.56 (3.19)	-2.20 (3.47)

No statistical analysis provided for Change in 7 point self monitored blood glucose profile

8. Secondary Outcome Measure: Change in body mass index (BMI) [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in body mass index (BMI)
Measure Description	Change in BMI from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	117	114
Change in body mass index (BMI) [units: kg/m^2] Least Squares Mean (Standard Error)
Baseline (Week 0)	34.49 (0.49)	33.71 (0.49)
Change at endpoint (Week 26)	-0.95 (0.11)	1.01 (0.11)

Statistical Analysis 1 for Change in body mass index (BMI)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	<0.001

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

9. Secondary Outcome Measure: Change in waist circumference [ Time Frame: 26 Weeks ]

Measure Type	Secondary
Measure Name	Change in waist circumference
Measure Description	Change in waist circumference from baseline to endpoint
Time Frame	26 Weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	117	113
Change in waist circumference [units: cm] Least Squares Mean (Standard Error)
Baseline (Week 0)	112.07 (1.30)	110.64 (1.32)
Change at endpoint (Week 26)	-2.19 (0.54)	1.97 (0.54)

Statistical Analysis 1 for Change in waist circumference

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	<0.001

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

10. Secondary Outcome Measure: Change in waist-to-hip ratio [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in waist-to-hip ratio
Measure Description	Change in waist-to-hip ratio from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	117	112
Change in waist-to-hip ratio [units: Ratio] Least Squares Mean (Standard Error)
Baseline (Week 0)	0.99 (0.01)	0.98 (0.01)
Change at endpoint (Week 26)	-0.02 (0.00)	0.01 (0.00)

Statistical Analysis 1 for Change in waist-to-hip ratio

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	<0.001

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

11. Secondary Outcome Measure: Change in body weight [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in body weight
Measure Description	Change in body weight from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	117	113
Change in body weight [units: kg] Least Squares Mean (Standard Error)
Baseline (Week 0)	101.19 (1.68)	97.93 (1.70)
Change at endpoint (Week 26)	-2.73 (0.31)	2.98 (0.31)

Statistical Analysis 1 for Change in body weight

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	<0.001

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

12. Secondary Outcome Measure: Percent change in body weight [ Time Frame: 26 Weeks ]

Measure Type	Secondary
Measure Name	Percent change in body weight
Measure Description	Percent change in baseline body weight at endpoint
Time Frame	26 Weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	117	113
Percent change in body weight [units: Percentage] Least Squares Mean (Standard Error)	-2.8 (0.3)	3.1 (0.3)

Statistical Analysis 1 for Percent change in body weight

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Models Repeated Measures]
P-Value^[4]	<0.001

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

13. Secondary Outcome Measure: Percent of patients achieving 5% weight loss [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percent of patients achieving 5% weight loss
Measure Description	Percent of patients who lost at least 5% of baseline body weight at endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward. For change in weight, patients should have a baseline and at least one post-baseline weight measurement. Otherwise, these patients are included as non-responders in the analysis.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Percent of patients achieving 5% weight loss [units: Percentage of participants]	19.5	0.9

Statistical Analysis 1 for Percent of patients achieving 5% weight loss

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.001
Odds Ratio (OR)^[5]	27.91
95% Confidence Interval	( 3.70 to 210.54 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

14. Secondary Outcome Measure: Percent of patients achieving 10% weight loss [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Percent of patients achieving 10% weight loss
Measure Description	Percent of patients who lost at least 10% of baseline body weight at endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward. For change in weight, patients should have a baseline and at least one post-baseline weight measurement. Otherwise, these patients are included as non-responders in the analysis.

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	116
Percent of patients achieving 10% weight loss [units: Percentage of participants]	4.2	0.0

No statistical analysis provided for Percent of patients achieving 10% weight loss

15. Secondary Outcome Measure: Change in systolic blood pressure [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in systolic blood pressure
Measure Description	Change in systolic blood pressure from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	117	113
Change in systolic blood pressure [units: mmHg] Least Squares Mean (Standard Error)
Baseline (Week 0)	134.0 (1.5)	134.7 (1.5)
Change at endpoint (Week 26)	-3.6 (1.2)	0.6 (1.2)

Statistical Analysis 1 for Change in systolic blood pressure

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	0.014

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

16. Secondary Outcome Measure: Change in diastolic blood pressure [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in diastolic blood pressure
Measure Description	Change in diastolic blood pressure from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	117	113
Change in diastolic blood pressure [units: mmHg] Least Squares Mean (Standard Error)
Baseline (Week 0)	79.6 (0.8)	79.7 (0.8)
Change at endpoint (Week 26)	-0.8 (0.7)	0.9 (0.7)

Statistical Analysis 1 for Change in diastolic blood pressure

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [Mixed Model Repeated Measures]
P-Value^[4]	0.100

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

17. Secondary Outcome Measure: Change in fasting serum total cholesterol (TC) [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in fasting serum total cholesterol (TC)
Measure Description	Change in TC from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	105	108
Change in fasting serum total cholesterol (TC) [units: mmol/L] Least Squares Mean (Standard Error)	-0.36 (0.07)	-0.21 (0.07)

Statistical Analysis 1 for Change in fasting serum total cholesterol (TC)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.125

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

18. Secondary Outcome Measure: Change in high density lipoprotein (HDL) cholesterol [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in high density lipoprotein (HDL) cholesterol
Measure Description	Change in HDL cholesterol from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	101	106
Change in high density lipoprotein (HDL) cholesterol [units: mmol/L] Least Squares Mean (Standard Error)	0.01 (0.01)	0.02 (0.01)

Statistical Analysis 1 for Change in high density lipoprotein (HDL) cholesterol

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.471

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

19. Secondary Outcome Measure: Change in TC to HDL cholesterol ratio [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in TC to HDL cholesterol ratio
Measure Description	Change in TC to HDL cholesterol ratio from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	101	106
Change in TC to HDL cholesterol ratio [units: Ratio] Least Squares Mean (Standard Error)	-0.40 (0.10)	-0.34 (0.09)

Statistical Analysis 1 for Change in TC to HDL cholesterol ratio

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.601

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

20. Secondary Outcome Measure: Change in fasting serum triglycerides [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in fasting serum triglycerides
Measure Description	Change in fasting serum triglycerides from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	105	108
Change in fasting serum triglycerides [units: mmol/L] Least Squares Mean (Standard Error)	-0.33 (0.08)	-0.38 (0.08)

Statistical Analysis 1 for Change in fasting serum triglycerides

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.650

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

21. Secondary Outcome Measure: Change in low density lipoprotein (LDL) cholesterol [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in low density lipoprotein (LDL) cholesterol
Measure Description	Change in LDL cholesterol from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	95	101
Change in low density lipoprotein (LDL) cholesterol [units: mmol/L] Least Squares Mean (Standard Error)	-0.25 (0.06)	-0.07 (0.05)

Statistical Analysis 1 for Change in low density lipoprotein (LDL) cholesterol

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.017

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

22. Secondary Outcome Measure: Change in apolipoprotein-B [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Change in apolipoprotein-B
Measure Description	Change in apolipoprotein-B from baseline to endpoint
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set, Last Observation Carried Forward

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	104	109
Change in apolipoprotein-B [units: g/L] Least Squares Mean (Standard Error)	-0.09 (0.02)	-0.08 (0.02)

Statistical Analysis 1 for Change in apolipoprotein-B

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.667

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

23. Secondary Outcome Measure: Incidence of hypoglycemic episodes [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Incidence of hypoglycemic episodes
Measure Description	Percent of total patients in each arm experiencing hypoglycemia at any point in the 26 week study
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	114
Incidence of hypoglycemic episodes [units: percent]	50.0	59.6

Statistical Analysis 1 for Incidence of hypoglycemic episodes

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.139
Odds Ratio (OR)^[5]	0.675
95% Confidence Interval	( 0.401 to 1.136 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

24. Secondary Outcome Measure: Incidence of nocturnal hypoglycemic episodes [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Incidence of nocturnal hypoglycemic episodes
Measure Description	Percent of total patients in each arm experiencing nocturnal hypoglycemia at any point in the 26 week study
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	114
Incidence of nocturnal hypoglycemic episodes [units: percent]	11.9	29.8

Statistical Analysis 1 for Incidence of nocturnal hypoglycemic episodes

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.001
Odds Ratio (OR)^[5]	0.317
95% Confidence Interval	( 0.159 to 0.630 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

25. Secondary Outcome Measure: Incidence of severe hypoglycemic episodes [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Incidence of severe hypoglycemic episodes
Measure Description	Percent of total patients in each arm experiencing severe hypoglycemia at any point during the 26 week study
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	114
Incidence of severe hypoglycemic episodes [units: percent]	4.2	5.3

Statistical Analysis 1 for Incidence of severe hypoglycemic episodes

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.716
Odds Ratio (OR)^[5]	0.797
95% Confidence Interval	( 0.235 to 2.705 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Odds Ratio (OR) = odds of a patient in the exenatide arm achieving the secondary outcome divided by the odds of a patient in the insulin glargine arm achieving the secondary outcome
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

26. Secondary Outcome Measure: Hypoglycemic rate per 30 days [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Hypoglycemic rate per 30 days
Measure Description	Number of hypoglycemic episodes per patient adjusted per 30 days
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	114
Hypoglycemic rate per 30 days [units: Number of episodes per 30 days] Median (Inter-Quartile Range)	0.069 (0.000 to 0.495)	0.164 (0.000 to 0.686)

Statistical Analysis 1 for Hypoglycemic rate per 30 days

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [ANCOVA on ranks]
P-Value^[4]	0.113

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

27. Secondary Outcome Measure: Nocturnal hypoglycemic rate per 30 days [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Nocturnal hypoglycemic rate per 30 days
Measure Description	Number of nocturnal hypoglycemic episodes per patient adjusted per 30 days
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	114
Nocturnal hypoglycemic rate per 30 days [units: Number of episodes per 30 days] Median (Inter-Quartile Range)	0.000 (0.000 to 0.000)	0.000 (0.000 to 0.163)

Statistical Analysis 1 for Nocturnal hypoglycemic rate per 30 days

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [ANCOVA on ranks]
P-Value^[4]	<0.001

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

28. Secondary Outcome Measure: Severe hypoglycemic rate per 30 days [ Time Frame: 26 weeks ]

Measure Type	Secondary
Measure Name	Severe hypoglycemic rate per 30 days
Measure Description	Number of severe hypoglycemic episodes per patient adjusted per 30 days
Time Frame	26 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Measured Values

	Exenatide	Insulin Glargine
Number of Participants Analyzed [units:participants]	118	114
Severe hypoglycemic rate per 30 days [units: Number of episodes per 30 days] Median (Full Range)	0.000 (0.000 to 0.989)	0.000 (0.000 to 0.328)

Statistical Analysis 1 for Severe hypoglycemic rate per 30 days

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [ANCOVA on ranks]
P-Value^[4]	0.740

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

Serious Adverse Events

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

Reporting Groups

	Description
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Serious Adverse Events

Exenatide

Insulin Glargine

Total, serious adverse events

# participants affected / at risk

5/---

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

1/---

0/---

# events

Cardiac disorders

Atrioventricular block complete¹,^†

# participants affected / at risk

0/---

1/---

# events

Infections and infestations

Campylobacter infection¹,^†

# participants affected / at risk

1/---

0/---

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

0/---

1/---

# events

Skin and subcutaneous tissue disorders

Cellulitis¹,^†

# participants affected / at risk

0/---

1/---

# events

Psychiatric disorders

Confusional state¹,^†

# participants affected / at risk

1/---

0/---

# events

Musculoskeletal and connective tissue disorders

Epistaxis¹,^†

# participants affected / at risk

0/---

1/---

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

1/---

0/---

# events

Metabolism and nutrition disorders

Hypoglycemia¹,^†

# participants affected / at risk

1/---

0/---

# events

Respiratory, thoracic and mediastinal disorders

Infective exacerbation of chronic obstructive airways disease¹

# participants affected / at risk

0/---

1/---

# events

Musculoskeletal and connective tissue disorders

Mobility decreased¹,^†

# participants affected / at risk

1/---

0/---

# events

Renal and urinary disorders

Renal failure acute¹,^†

# participants affected / at risk

1/---

0/---

# events

Cardiac disorders

Supraventricular tachycardia¹,^†

# participants affected / at risk

1/---

0/---

# events

Injury, poisoning and procedural complications

Wrong drug administered¹,^†

# participants affected / at risk

0/---

1/---

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
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
Exenatide	5mcg twice daily for 4 weeks, followed by 10mcg twice daily for 22 weeks
Insulin Glargine	dosing based on treat to target protocol

Other Adverse Events

Exenatide

Insulin Glargine

Total, other (not including serious) adverse events

# participants affected / at risk

105/---

94/---

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

57/---

3/---

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

24/---

23/---

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

22/---

14/---

Nervous system disorders

Headache¹,^†

# participants affected / at risk

17/---

18/---

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

25/---

6/---

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

10/---

12/---

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

19/---

1/---

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

20/---

0/---

General disorders and administration site conditions

Early satiety¹,^†

# participants affected / at risk

20/---

0/---

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

18/---

1/---

Infections and infestations

Influenza¹,^†

# participants affected / at risk

8/---

11/---

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

3/---

15/---

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

5/---

12/---

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

4/---

13/---

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pain¹,^†

# participants affected / at risk

5/---

10/---

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

5/---

9/---

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

14/---

0/---

Gastrointestinal disorders

Eructation¹,^†

# participants affected / at risk

13/---

0/---

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

12/---

0/---

Metabolism and nutrition disorders

Anorexia¹,^†

# participants affected / at risk

11/---

1/---

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

10/---

0/---

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

6/---

4/---

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

1/---

8/---

General disorders and administration site conditions

Injection site bruising¹,^†

# participants affected / at risk

6/---

2/---

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

2/---

6/---

Gastrointestinal disorders

Bowel sounds abnormal¹,^†

# participants affected / at risk

7/---

0/---

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

6/---

1/---

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
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:

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:	Peter Ohman, Medical Science Director
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center null

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Mauricio Silva de Lima

Eli Lilly and Company

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site