Effects of Exenatide and Insulin Glargine in Subjects with Type 2 Diabetes

Study identifier:2993-114

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 3, Randomized, Open Label, Comparator-Controlled, Parallel Group, Multicenter Study to Compare the Effects of Exenatide and Insulin Glargine on Beta Cell Function and Cardiovascular Risk Markers in Subjects with Type 2 Diabetes Treated with Metformin who have not Achieved Target HbA1c

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 3

Healthy volunteers

Study drug

exenatide, Insulin glargine, Metformin

Sex

All

Actual Enrollment

Study type

Interventional

Age

30 Years - 75 Years

Date

Study Start Date: 01 Sept 2004

Primary Completion Date: 01 Dec 2009

Study Completion Date: 01 Dec 2009

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

Amsterdam, Netherlands

Location

Research Site

Goteborg, Sweden

Location

Research Site

Helsinki, Finland

Arms	Assigned Interventions
Experimental: Exenatide Arm Exenatide and Metformin	Drug: exenatide subcutaneous injection, titrated up to a maximum of 20mcg three times a day in order to meet defined blood glucose targets Other Name: Byetta Drug: Metformin Patients usual dosage
Active Comparator: Insulin Glargine Arm Insulin Glargine and Metformin	Drug: Insulin glargine subcutaneous injection, once a day, titrated as necessary in order to meet defined blood glucose targets Other Name: Lantus Drug: Metformin Patients usual dosage

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Participant Flow for 2 periods

Period 1: On-drug period (Week 0 to Week 52)

	Exenatide Arm	Insulin Glargine Arm
STARTED	36	33
COMPLETED	30^[1]	30^[2]
NOT COMPLETED	6	3
Withdrawal of consent	1	1
Adverse Event	5	0
Physician Decision	0	1
Lost to Follow-up	0	1

[1]	Subjects experiencing loss of glucose control after Week 52 are considered to have completed study.
[2]	Subjects experiencing loss of glucose control after Week 52 are considered to have completed study.

Period 2: Off-drug period (Week 52 to Week 64)

	Exenatide Arm	Insulin Glargine Arm
STARTED	30^[1]	30^[2]
COMPLETED	25	26
NOT COMPLETED	5	4
Withdrawal of consent	2	1
Physician Decision	0	1
Loss of glucose control	3	2

[1]	Exenatide is discontinued, metformin is continued
[2]	Insulin Glargine is discontinued, metformin is continued

Baseline Characteristics

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

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Baseline Measures

	Exenatide Arm	Insulin Glargine Arm	Total
Number of Participants [units: Participants]	36	33	69
Age Continuous [units: years] Mean ± Standard Deviation	58.4 ± 8.4	58.3 ± 7.3	58.4 ± 7.8
Gender, Male/Female [units: participants]
Female	13	11	24
Male	23	22	45
Body Mass Index (BMI) [units: kg/m^2] Mean ± Standard Deviation	30.87 ± 4.15	30.13 ± 3.49	30.52 ± 3.84
Body weight [units: kg] Mean ± Standard Deviation	90.56 ± 12.66	92.39 ± 13.56	91.44 ± 13.03
Glycosylated hemoglobin (HbA1c) [units: percentage] Mean ± Standard Deviation	7.58 ± 0.89	7.41 ± 0.81	7.50 ± 0.85
Duration of diabetes [units: years] Mean ± Standard Deviation	5.72 ± 4.70	3.97 ± 3.62	4.88 ± 4.28

Outcome Measures

1. Primary Outcome Measure: Beta-cell function after 52 weeks of therapy [ Time Frame: Baseline (week -2) and 52 weeks ]

Measure Type	Primary
Measure Name	Beta-cell function after 52 weeks of therapy
Measure Description	Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]).
Time Frame	Baseline (week -2) and 52 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.
Evaluable population

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	30	30
Beta-cell function after 52 weeks of therapy [units: ratio] Least Squares Mean (Standard Error)	2.89 (0.27)	1.15 (0.11)

Statistical Analysis 1 for Beta-cell function after 52 weeks of therapy

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0001

[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.

2. Secondary Outcome Measure: Beta-cell function 4 weeks after cessation of therapy [ Time Frame: Baseline (week -2) and 56 weeks ]

Measure Type	Secondary
Measure Name	Beta-cell function 4 weeks after cessation of therapy
Measure Description	Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline [week -2]).
Time Frame	Baseline (week -2) and 56 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.
Evaluable population

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	30	30
Beta-cell function 4 weeks after cessation of therapy [units: ratio] Least Squares Mean (Standard Error)	1.02 (0.06)	1.08 (0.07)

Statistical Analysis 1 for Beta-cell function 4 weeks after cessation of therapy

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.4185

[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.

3. Secondary Outcome Measure: Change in first phase C-peptide release [ Time Frame: baseline (week -2), 52 weeks, and 56 weeks ]

Measure Type	Secondary
Measure Name	Change in first phase C-peptide release
Measure Description	Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure.
Time Frame	baseline (week -2), 52 weeks, and 56 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.
Evaluable population. Last observation carried forward.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	29	30
Change in first phase C-peptide release [units: ratio] Least Squares Mean (Standard Error)
52 weeks	1.72 (0.11)	1.13 (0.07)
56 weeks	0.95 (0.05)	1.06 (0.06)

Statistical Analysis 1 for Change in first phase C-peptide release

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical analysis at week 52.
[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.

Statistical Analysis 2 for Change in first phase C-peptide release

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.1188

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical analysis at week 56.
[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: Change in second phase C-peptide release [ Time Frame: baseline (-2 weeks), 52 weeks, and 56 weeks ]

Measure Type	Secondary
Measure Name	Change in second phase C-peptide release
Measure Description	Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure.
Time Frame	baseline (-2 weeks), 52 weeks, and 56 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.
Evaluable population. Last observation carried forward.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	30	30
Change in second phase C-peptide release [units: ratio] Least Squares Mean (Standard Error)
52 weeks	2.88 (0.18)	1.01 (0.07)
56 weeks	1.00 (0.05)	1.08 (0.06)

Statistical Analysis 1 for Change in second phase C-peptide release

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical analysis at week 52.
[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.

Statistical Analysis 2 for Change in second phase C-peptide release

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.1996

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Statistical analysis at week 56.
[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. Secondary Outcome Measure: Change in glycosylated hemoglobin (HbA1c) [ Time Frame: Week 0 and week 52 ]

Measure Type	Secondary
Measure Name	Change in glycosylated hemoglobin (HbA1c)
Measure Description	Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0).
Time Frame	Week 0 and week 52
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.
Intent to treat population. Last observation carried forward.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	36	33
Change in glycosylated hemoglobin (HbA1c) [units: percent] Least Squares Mean (Standard Error)	-0.97 (0.14)	-0.87 (0.15)

Statistical Analysis 1 for Change in glycosylated hemoglobin (HbA1c)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.5522

[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.

6. Secondary Outcome Measure: Change in fasting plasma glucose [ Time Frame: 0 weeks and 52 weeks ]

Measure Type	Secondary
Measure Name	Change in fasting plasma glucose
Measure Description	Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0).
Time Frame	0 weeks and 52 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.
Intent to treat population. Last observation carried forward.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	36	33
Change in fasting plasma glucose [units: mmol/L] Least Squares Mean (Standard Error)	-1.53 (0.25)	-3.10 (0.27)

Statistical Analysis 1 for Change in fasting plasma glucose

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001

[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.

7. Secondary Outcome Measure: Seven point self monitored blood glucose (SMBG) measurements [ Time Frame: 0 weeks and 52 weeks ]

Measure Type	Secondary
Measure Name	Seven point self monitored blood glucose (SMBG) measurements
Measure Description	SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime).
Time Frame	0 weeks and 52 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.
Intent to treat population.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	36	33
Seven point self monitored blood glucose (SMBG) measurements [units: mmol/L] Mean (Standard Deviation)
Pre-breakfast measurement (week 0)	8.92 (1.80)	8.38 (1.91)
Pre-breakfast measurement (week 52)	7.27 (1.63)	5.63 (0.85)
2-hour post-breakfast measurement (week 0)	11.00 (2.58)	11.17 (3.30)
2-hour post-breakfast measurement (week 52)	6.98 (2.42)	7.53 (2.16)
Pre-lunch measurement (week 0)	8.14 (2.25)	8.54 (2.51)
Pre-lunch measurement (week 52)	6.52 (1.52)	6.24 (1.66)
2-hour post-lunch measurement (week 0)	9.90 (2.54)	10.52 (2.96)
2-hour post-lunch measurement (week 52)	7.97 (2.01)	8.15 (1.77)
Pre-dinner measurement (week 0)	8.38 (2.40)	8.07 (2.48)
Pre-dinner measurement (week 52)	7.53 (2.63)	6.98 (2.04)
2-hour post-dinner measurement (week 0)	10.42 (2.42)	10.26 (2.82)
2-hour post-dinner measurement (week 52)	6.98 (2.25)	8.81 (2.03)
Bedtime measurement (week 0)	9.76 (2.44)	9.85 (3.09)
Bedtime measurement (week 52)	7.61 (2.11)	8.03 (2.82)

No statistical analysis provided for Seven point self monitored blood glucose (SMBG) measurements

8. Secondary Outcome Measure: Change in body weight [ Time Frame: 0 weeks and 52 weeks ]

Measure Type	Secondary
Measure Name	Change in body weight
Measure Description	Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0).
Time Frame	0 weeks and 52 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.
Intent to treat population. Last observation carried forward.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	36	33
Change in body weight [units: kg] Least Squares Mean (Standard Error)	-3.80 (0.87)	0.75 (0.95)

Statistical Analysis 1 for Change in body weight

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	<0.0001

[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: M-value at baseline, week 52 and week 56 [ Time Frame: baseline (week -2), 52 weeks, and 56 weeks ]

Measure Type	Secondary
Measure Name	M-value at baseline, week 52 and week 56
Measure Description	M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp.
Time Frame	baseline (week -2), 52 weeks, and 56 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.
Evaluable population.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Measured Values

	Exenatide Arm	Insulin Glargine Arm
Number of Participants Analyzed [units:participants]	30	30
M-value at baseline, week 52 and week 56 [units: mg/min/kg] Mean (Standard Error)
baseline (week -2)	2.24 (0.39)	2.79 (0.26)
week 52	3.18 (0.42)	3.85 (0.32)
week 56	3.19 (0.44)	2.81 (0.29)

No statistical analysis provided for M-value at baseline, week 52 and week 56

Serious Adverse Events

Time Frame	Total reporting period for adverse events is 64 weeks: a 52-week on-drug period followed by a 12-week off-drug period.
Additional Description	No text entered.

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Serious Adverse Events

Exenatide Arm

Insulin Glargine Arm

Total, serious adverse events

# participants affected / at risk

3/36 (8.33%)

1/33 (3.03%)

Cardiac disorders

Coronary Artery Stenosis¹

# participants affected / at risk

1/36 (2.78%)

0/33 (0.00%)

Gastrointestinal disorders

Pancreatitis¹

# participants affected / at risk

1/36 (2.78%)

0/33 (0.00%)

Infections and infestations

Diverticulitis¹

# participants affected / at risk

1/36 (2.78%)

0/33 (0.00%)

Vascular disorders

Thrombophlebitis Superficial¹

# participants affected / at risk

0/36 (0.00%)

1/33 (3.03%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 6.1

Other Adverse Events

Time Frame	Total reporting period for adverse events is 64 weeks: a 52-week on-drug period followed by a 12-week off-drug period.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Exenatide Arm	5 mcg twice a day for 4 weeks, followed by 10 mcg twice a day for 8 weeks. After 12 weeks, exenatide is titrated (up to a maximum of 20 mcg three times a day) based on periodic glycosylated hemoglobin (HbA1c) measurements and tolerability.
Insulin Glargine Arm	Dosing starts at 10 IU/day, and is then titrated, based on daily fasting blood glucose measurements.

Other Adverse Events

Exenatide Arm

Insulin Glargine Arm

Total, other (not including serious) adverse events

# participants affected / at risk

32/36 (88.89%)

31/33 (93.94%)

Blood and lymphatic system disorders

Anemia¹

# participants affected / at risk

1/36 (2.78%)

4/33 (12.12%)

Gastrointestinal disorders

Abdominal Distension¹

# participants affected / at risk

4/36 (11.11%)

0/33 (0.00%)

Gastrointestinal disorders

Diarrhea¹

# participants affected / at risk

3/36 (8.33%)

1/33 (3.03%)

Gastrointestinal disorders

Dyspepsia¹

# participants affected / at risk

5/36 (13.89%)

2/33 (6.06%)

Gastrointestinal disorders

Flatulence¹

# participants affected / at risk

3/36 (8.33%)

0/33 (0.00%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

18/36 (50.00%)

0/33 (0.00%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

4/36 (11.11%)

0/33 (0.00%)

General disorders and administration site conditions

Injection Site Rash¹

# participants affected / at risk

3/36 (8.33%)

0/33 (0.00%)

General disorders and administration site conditions

Edema Peripheral¹

# participants affected / at risk

0/36 (0.00%)

2/33 (6.06%)

Infections and infestations

Gastroenteritis¹

# participants affected / at risk

1/36 (2.78%)

4/33 (12.12%)

Infections and infestations

Influenza¹

# participants affected / at risk

5/36 (13.89%)

9/33 (27.27%)

Infections and infestations

Laryngitis¹

# participants affected / at risk

2/36 (5.56%)

1/33 (3.03%)

Infections and infestations

Tooth Infection¹

# participants affected / at risk

0/36 (0.00%)

2/33 (6.06%)

Infections and infestations

Urinary Tract Infection¹

# participants affected / at risk

3/36 (8.33%)

2/33 (6.06%)

Metabolism and nutrition disorders

Decreased Appetite¹

# participants affected / at risk

3/36 (8.33%)

0/33 (0.00%)

Metabolism and nutrition disorders

Hyperlipidemia¹

# participants affected / at risk

0/36 (0.00%)

3/33 (9.09%)

Metabolism and nutrition disorders

Hypoglycemia¹

# participants affected / at risk

6/36 (16.67%)

10/33 (30.30%)

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

2/36 (5.56%)

4/33 (12.12%)

Nervous system disorders

Headache¹

# participants affected / at risk

1/36 (2.78%)

2/33 (6.06%)

Renal and urinary disorders

Proteinuria¹

# participants affected / at risk

2/36 (5.56%)

0/33 (0.00%)

Vascular disorders

Hypertension¹

# participants affected / at risk

0/36 (0.00%)

2/33 (6.06%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 6.1

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

Vice President, Research and Development

Amylin Pharmaceuticals

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Trial Results Summaries