Addition Of Exenatide To Insulin Glargine In Type 2 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT00765817
• Recruitment Status: Completed
• First Posted: October 3, 2008
• Results First Posted: January 26, 2011
• Last Update Posted: October 24, 2016
• Sponsor: AstraZeneca
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Type 2 Diabetes
• Interventions: Drug: placebo; Drug: exenatide
• Enrollment: 261

Participant Flow

Recruitment Details
Pre-assignment Details	Two subjects who started the study, subsequently withdrew prior to receiving study medication and are not part of the full analysis set

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Period Title: Overall Study
Started	138 [1]	123 [1]
Completed	112	101
Not Completed	26	22
Reason Not Completed
Adverse Event	13	1
Death	0	1
Entry criteria not met	2	2
Loss of glucose control	0	2
Lost to Follow-up	1	3
Physician Decision	2	1
Protocol Violation	1	1
Subject decision	7	11
[1] One subject withdrew prior to receiving study medication, not included in analysis set

Baseline Characteristics

Arm/Group Title		Exenatide Arm	Placebo Arm	Total
Arm/Group Description		Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)	Total of all reporting groups
Overall Number of Baseline Participants		137	122	259
Baseline Analysis Population Description		One subject per group withdrew from the study prior to the first dose of study medication and therefore are not part of the baseline or subsequent analysis.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	137 participants	122 participants	259 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	100 73.0%	84 68.9%	184 71.0%
	>=65 years	37 27.0%	38 31.1%	75 29.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	137 participants	122 participants	259 participants
		58.67 (8.91)	59.40 (9.96)	59.01 (9.41)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	137 participants	122 participants	259 participants
	Female	67 48.9%	44 36.1%	111 42.9%
	Male	70 51.1%	78 63.9%	148 57.1%

Outcome Measures

1. Primary Outcome

Title	Change in Glycosylated Hemoglobin (HbA1c)
Description	Change in HbA1c from baseline following 30 weeks of therapy (i.e., HbA1c at week 30 minus HbA1c at baseline). Unit of measure is percent of hemoglobin that is glycosylated.
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	112	100
Least Squares Mean (Standard Error); Unit of Measure: percentage of hemoglobin
	-1.71 (0.09)	-1.00 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Patients Achieving HbA1c <=7%
Description	Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 30 (percentage = [number of subjects with HbA1c <=7% at week 30 divided by number of subjects with HbA1c >7% at baseline] * 100%).
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Only patients with baseline HbA1c > target were included in calculation.

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	127	106
Measure Type: Number; Unit of Measure: percentage
	58.3	31.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Patients Achieving HbA1c <=6.5%
Description	Percentage of patients in each arm who had HbA1c >6.5% at baseline and had HbA1c <=6.5% at week 30 (percentage = [number of subjects with HbA1c <=6.5% at week 30 divided by number of subjects with HbA1c >6.5% at baseline] * 100%).
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Only patients with baseline HbA1c > target were included in calculation.

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	131	113
Measure Type: Number; Unit of Measure: percentage
	42.0	13.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

4. Secondary Outcome

Title	Change in Fasting Serum Glucose
Description	Change in fasting serum glucose following 30 weeks of therapy (i.e., fasting serum glucose at week 30 minus fasting serum glucose at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	111	98
Least Squares Mean (Standard Error); Unit of Measure: mmol/L
	-1.28 (0.2)	-0.87 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.174
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

5. Secondary Outcome

Title	Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Description	Change in 7-point (pre-breakfast, 2 hour post-breakfast, pre-lunch, 2 hour post-lunch, pre-dinner, 2 hour post-dinner, 0300 hours) SMBG profile from baseline to week 30 (change = blood glucose value at week 30 minus blood glucose value at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	108	89
Least Squares Mean (Standard Error); Unit of Measure: mmol/L
Pre-breakfast: baseline	7.89 (0.2)	8.27 (0.2)
Pre-breakfast: change at week 30	-1.58 (0.1)	-1.48 (0.1)
2 hour post-breakfast: baseline	10.89 (0.2)	11.82 (0.2)
2 hour post-breakfast: change at week 30	-3.56 (0.2)	-1.72 (0.2)
Pre-lunch: baseline	8.95 (0.2)	9.77 (0.2)
Pre-lunch: change at week 30	-2.23 (0.2)	-1.15 (0.2)
2 hour post-lunch: baseline	11.35 (0.2)	11.70 (0.2)
2 hour post-lunch: change at week 30	-2.74 (0.2)	-1.38 (0.2)
Pre-dinner: baseline	9.85 (0.2)	9.99 (0.2)
Pre-dinner: change at week 30	-2.25 (0.2)	-1.33 (0.2)
2 hour post-dinner: baseline	12.03 (0.3)	11.86 (0.3)
2 hour post-dinner: change at week 30	-3.87 (0.2)	-1.34 (0.3)
0300: baseline	8.95 (0.2)	9.20 (0.2)
0300: change at week 30	-2.27 (0.2)	-1.48 (0.2)

6. Secondary Outcome

Title	Change in Total Cholesterol
Description	Change in total cholesterol following 30 weeks of therapy (i.e., total cholesterol at week 30 minus total cholesterol at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	110	98
Least Squares Mean (Standard Error); Unit of Measure: mmol/L
	-0.16 (0.08)	-0.02 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.203
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

7. Secondary Outcome

Title	Change in Low Density Lipoprotein (LDL) Cholesterol
Description	Change in LDL cholesterol following 30 weeks of therapy (i.e., LDL cholesterol at week 30 minus LDL cholesterol at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	102	97
Least Squares Mean (Standard Error); Unit of Measure: mmol/L
	-0.19 (0.07)	-0.00 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.063
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

8. Secondary Outcome

Title	Change in High Density Lipoprotein (HDL) Cholesterol
Description	Change in HDL cholesterol following 30 weeks of therapy (i.e., HDL cholesterol at week 30 minus HDL cholesterol at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	110	98
Least Squares Mean (Standard Error); Unit of Measure: mmol/L
	0.01 (0.02)	0.00 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.745
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

9. Secondary Outcome

Title	Change in Triglycerides
Description	Change in triglycerides following 30 weeks of therapy (i.e., triglycerides at week 30 minus triglycerides at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	110	98
Least Squares Mean (Standard Error); Unit of Measure: mmol/L
	-0.02 (0.09)	-0.03 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.933
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

10. Secondary Outcome

Title	Change in Body Weight
Description	Change in body weight following 30 weeks of therapy (i.e., body weight at week 30 minus body weight at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	112	101
Least Squares Mean (Standard Error); Unit of Measure: kg
	-1.78 (0.3)	0.96 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

11. Secondary Outcome

Title	Change in Waist Circumference
Description	Change in waist circumference following 30 weeks of therapy (i.e., waist circumference at week 30 minus waist circumference at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	137	120
Least Squares Mean (Standard Error); Unit of Measure: cm
	-1.08 (0.52)	-0.25 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.226
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

12. Secondary Outcome

Title	Change in Daily Insulin Dose
Description	Change in daily insulin dose following 30 weeks of therapy (i.e., daily insulin dose at week 30 minus daily insulin dose at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	110	100
Least Squares Mean (Standard Error); Unit of Measure: insulin units (U)
	13.19 (2.02)	19.71 (2.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.026
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

13. Secondary Outcome

Title	Change in Daily Insulin Dose (on a Per Body Weight Basis)
Description	Change in daily insulin dose per kilogram (kg) following 30 weeks of therapy (i.e., daily insulin dose per kg at week 30 minus daily insulin dose per kg at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	110	100
Least Squares Mean (Standard Error); Unit of Measure: insulin units per kg (U/kg)
	0.15 (0.02)	0.20 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.070
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

14. Secondary Outcome

Title	Change in Systolic Blood Pressure (SBP)
Description	Change in SBP following 30 weeks of therapy (i.e., SBP at week 30 minus SBP at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	112	101
Least Squares Mean (Standard Error); Unit of Measure: mmHg
	-2.74 (1.2)	1.71 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.011
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

15. Secondary Outcome

Title	Change in Diastolic Blood Pressure (DBP)
Description	Change in DBP following 30 weeks of therapy (i.e., DBP at week 30 minus DBP at baseline)
Time Frame	baseline and 30 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set, Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	112	101
Least Squares Mean (Standard Error); Unit of Measure: mmHg
	-1.73 (0.6)	1.69 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

16. Secondary Outcome

Title	Minor Hypoglycemia Rate Per Year
Description	Number of minor hypoglycemia events experienced per subject per year. Minor hypoglycemia was defined as any time a subject felt he or she was experiencing a sign or symptom associated with hypoglycemia that was either self-treated by the subject or resolved on its own and had a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL).
Time Frame	baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	137	122
Mean (Standard Deviation); Unit of Measure: events per subject per year
	1.61 (5.94)	1.55 (4.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.666
	Comments	[Not Specified]
	Method	Negative binomial regression model
	Comments	[Not Specified]

17. Secondary Outcome

Title	Percentage of Subjects Experiencing Minor Hypoglycemia
Description	Percentage of subjects in each arm experiencing at least one episode of minor hypoglycemia at any point during the study. Minor hypoglycemia was defined as any time a subject felt he or she was experiencing a sign or symptom associated with hypoglycemia that was either self-treated by the subject or resolved on its own and had a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL).
Time Frame	baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description:	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
Overall Number of Participants Analyzed	137	122
Measure Type: Number; Unit of Measure: percentage
	24.8	28.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Arm, Placebo Arm
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.486
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Exenatide Arm	Placebo Arm
Arm/Group Description	Exenatide 5mcg twice daily for 4 weeks, followed by exenatide 10mcg twice daily for 26 weeks (with a background of titrated insulin glargine and other oral antidiabetic agents)	Placebo volume equivalent to the active volume injected in the exenatide arm (with a background of titrated insulin glargine and other oral antidiabetic agents)
All-Cause Mortality
	Exenatide Arm	Placebo Arm
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Exenatide Arm	Placebo Arm
	Affected / at Risk (%)	Affected / at Risk (%)
Total	8/137 (5.84%)	11/122 (9.02%)
Cardiac disorders
Angina unstable * 1	0/137 (0.00%)	1/122 (0.82%)
Coronary artery occlusion * 1	1/137 (0.73%)	0/122 (0.00%)
Myocardial infarction * 1	0/137 (0.00%)	1/122 (0.82%)
Palpitations * 1	0/137 (0.00%)	1/122 (0.82%)
Transient ischemic attack * 1	0/137 (0.00%)	1/122 (0.82%)
Gastrointestinal disorders
Small intestine obstruction * 1	0/137 (0.00%)	1/122 (0.82%)
General disorders
Chest pain * 1	1/137 (0.73%)	1/122 (0.82%)
Infections and infestations
Herpes zoster * 1	1/137 (0.73%)	0/122 (0.00%)
Sepsis * 1	0/137 (0.00%)	1/122 (0.82%)
Staphylococcal infection * 1	1/137 (0.73%)	0/122 (0.00%)
Injury, poisoning and procedural complications
Accidental overdose * 1	1/137 (0.73%)	0/122 (0.00%)
Ankle fracture * 1	0/137 (0.00%)	1/122 (0.82%)
Eye penetration * 1	1/137 (0.73%)	0/122 (0.00%)
Fall * 1	1/137 (0.73%)	0/122 (0.00%)
Metabolism and nutrition disorders
Hypoglycemia * 1	0/137 (0.00%)	1/122 (0.82%)
Musculoskeletal and connective tissue disorders
Osteoarthritis * 1	2/137 (1.46%)	0/122 (0.00%)
Psychiatric disorders
Suicide attempt * 1	0/137 (0.00%)	1/122 (0.82%)
Renal and urinary disorders
Cystitis * 1	0/137 (0.00%)	1/122 (0.82%)
Respiratory, thoracic and mediastinal disorders
Dyspnea * 1	1/137 (0.73%)	0/122 (0.00%)
Pulmonary embolism * 1	0/137 (0.00%)	1/122 (0.82%)
Skin and subcutaneous tissue disorders
Uticaria * 1	0/137 (0.00%)	1/122 (0.82%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 12.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Exenatide Arm	Placebo Arm
	Affected / at Risk (%)	Affected / at Risk (%)
Total	109/138 (78.99%)	66/123 (53.66%)
Gastrointestinal disorders
Nausea * 1	56/138 (40.58%)	10/123 (8.13%)
Diarrhea * 1	25/138 (18.12%)	10/123 (8.13%)
Vomiting * 1	25/138 (18.12%)	5/123 (4.07%)
Constipation * 1	14/138 (10.14%)	2/123 (1.63%)
Dyspepsia * 1	9/138 (6.52%)	2/123 (1.63%)
General disorders
Asthenia * 1	7/138 (5.07%)	1/123 (0.81%)
Infections and infestations
Nasopharyngitis * 1	8/138 (5.80%)	6/123 (4.88%)
Musculoskeletal and connective tissue disorders
Back Pain * 1	9/138 (6.52%)	2/123 (1.63%)
Nervous system disorders
Headache * 1	19/138 (13.77%)	5/123 (4.07%)
Dizziness * 1	6/138 (4.35%)	7/123 (5.69%)
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection * 1	11/138 (7.97%)	9/123 (7.32%)
Cough * 1	7/138 (5.07%)	7/123 (5.69%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 12.0

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

• Name/Title: Peter Ohman, Medical Science Director
• Organization: AstraZeneca
• EMail: ClinicalTrialTransparency@astrazeneca.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Buse JB, Han J, Miller S, MacConell L, Pencek R, Wintle M. Addition of exenatide BID to insulin glargine: a post-hoc analysis of the effect on glycemia and weight across a range of insulin titration. Curr Med Res Opin. 2014 Jul;30(7):1209-18. doi: 10.1185/03007995.2014.896329. Epub 2014 Mar 18.

Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C; NN1250-3579 (BEGIN Once Long) Trial Investigators. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care. 2012 Dec;35(12):2464-71. doi: 10.2337/dc12-1205. Epub 2012 Oct 5.

Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.

Rosenstock J, Shenouda SK, Bergenstal RM, Buse JB, Glass LC, Heilmann CR, Kwan AY, MacConell LA, Hoogwerf BJ. Baseline factors associated with glycemic control and weight loss when exenatide twice daily is added to optimized insulin glargine in patients with type 2 diabetes. Diabetes Care. 2012 May;35(5):955-8. doi: 10.2337/dc11-1434. Epub 2012 Mar 19.

Buse JB, Bergenstal RM, Glass LC, Heilmann CR, Lewis MS, Kwan AY, Hoogwerf BJ, Rosenstock J. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011 Jan 18;154(2):103-12. doi: 10.7326/0003-4819-154-2-201101180-00300. Epub 2010 Dec 6.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00765817
• Other Study ID Numbers: H8O-US-GWCO
• First Submitted: October 1, 2008
• First Posted: October 3, 2008
• Results First Submitted: January 4, 2011
• Results First Posted: January 26, 2011
• Last Update Posted: October 24, 2016