Study to Evaluate the Efficacy and Safety of Exenatide Once-Weekly Injection Compared to Once-Daily Insulin in Type 2 Diabetes Mellitus

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00935532
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 427
• Locations: 22
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 19.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The objectives of this clinical trial are to compare the effects of exenatide once weekly and insulin glargine on blood glucose control, body weight, lipids, safety, and tolerability.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: exenatide once weekly; Drug: insulin glargine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 427 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Parallel Group Study to Evaluate the Efficacy and Safety of Exenatide Once-Weekly Injection Compared to Once-Daily Insulin in Type 2 Diabetes Mellitus Treated With Oral Antidiabetic(s)
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: exenatide once weekly	Drug: exenatide once weekly; subcutaneous injection, 2.0mg, once a week;
Active Comparator: insulin glargine	Drug: insulin glargine; subcutaneous injection, titrated to achieve fasting serum glucose target, once a day; Other Names: insulin glargine-Lantus

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c From Baseline to Endpoint (Week 26) [Baseline, Week 26]

   Change in HbA1c from baseline to endpoint (Week 26).

Secondary Outcome Measures

1. Percentage of Subjects Achieving HbA1c<=7% [Baseline, Week 26]

   Percentage of subjects achieving HbA1c <=7.0% (for subjects with HbA1c >7% at baseline)

2. Percentage of Subjects Achieving HbA1c<=6.5% [Baseline, Week 26]

   Percentage of subjects achieving HbA1c <=6.5% (for subjects with HbA1c >6.5% at baseline)

3. Change in Fasting Serum Glucose (FSG) From Baseline to Endpoint (Week 26) [Baseline, Week 26]

   Change in FSG (centralized measurement) from baseline to endpoint (Week 26)

4. Change in Body Weight From Baseline to Endpoint (Week 26) [Baseline, Week 26]

   Change in Body Weight from baseline to endpoint (Week 26)

5. Change in Total Cholesterol From Baseline to Endpoint (Week 26) [Baseline, Week 26]

   Change in Total Cholesterol from baseline to endpoint (Week 26)

6. Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Endpoint (Week 26) [Baseline, Week 26]

   Change in HDL-C from baseline to endpoint (Week 26)

7. Ratio of Fasting Triglycerides at Endpoint (Week 26) to Baseline [Baseline, Week 26]

   Ratio of Triglycerides (measured in mg/dL) at endpoint (Week 26) to Baseline. Log(Postbaseline Triglycerides) - log(Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.

8. Change in Blood Pressure From Baseline to Endpoint (Week 26) [Baseline, Week 26]

   Change in Blood Pressure from baseline to endpoint (Week 26)

9. Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events [Baseline to Week 26]

   Major confirmed hypoglycemia was defined as (1) any event accompanying symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure but resolved promptly in response to administration of glucagon or (2) glucose, or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) requiring assistance because of severe impairment in consciousness or motor activity whether or not symptoms of hypoglycemia were felt by the patient. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS.

10. Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events [Baseline to Week 26]

    Minor confirmed hypoglycemia was defined as any event a patient felt that he or she was experiencing a sign or symptom associated with hypoglycemia that resolved by self-treatment or on its own, and a concurrent self-monitoring fingerstick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• present with type 2 diabetes mellitus

• HbA1c between 7.1% and 11.0% inclusive

• body mass index (BMI) of >18kg/m2 and <35kg/m2, inclusive

• treated with a stable dose regimen of either of biguanide (BG) alone, BG + thiazolidinedione (TZD), BG + sulfonylurea (SU), or BG + TZD + SU for 90 days prior to study start

Exclusion Criteria:

• Have received chronic (>14 consecutive days) systemic adrenocorticosteroid therapy by oral, intravenous, or intramuscular route or intraarticular steroid injection within 4 weeks prior to study start.

• Have been treated with drugs that promote weight loss within 90 days prior to study start.

• Have been treated with drugs that directly affect gastrointestinal motility for > 21 consecutive days within 90 days prior to study start.

• Have had prior exposure to exenatide BID or QW or participated in the clinical trial of exenatide BID or QW (including the case that the study drug was not administered).

• Have been treated for >2 consecutive weeks with any of the following excluded medications within 90 days prior to study start: Insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 analogs

• Have received treatment within 30 days prior to study start drug that has not received regulatory approval for any indication.

• Are currently enrolled in any other clinical study or participated in and completed the clinical study within 30 days prior to study start.

• Have donated blood within 30 days prior to study start.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Aomori		Japan
2	Research Site	Chiba		Japan
3	Research Site	Ehime		Japan
4	Research Site	Fukuoka		Japan
5	Research Site	Gunma		Japan
6	Research Site	Hiroshima		Japan
7	Research Site	Hokkaido		Japan
8	Research Site	Hyogo		Japan
9	Research Site	Ibaragi		Japan
10	Research Site	Kagawa		Japan
11	Research Site	Kanagawa		Japan
12	Research Site	Kumamoto		Japan
13	Research Site	Kyoto		Japan
14	Research Site	Nagano		Japan
15	Research Site	Nagasaki		Japan
16	Research Site	Nara		Japan
17	Research Site	Oita		Japan
18	Research Site	Osaka		Japan
19	Research Site	Saitama		Japan
20	Research Site	Shizuoka		Japan
21	Research Site	Tokyo		Japan
22	Research Site	Toyama		Japan

Sponsors and Collaborators

• AstraZeneca
• Eli Lilly and Company

Investigators

• Study Director: Chief Medical Officer, MD, Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00935532
• Other Study ID Numbers: H8O-JE-GWBX
• First Posted: Jul 9, 2009
• Last Update Posted: Jun 15, 2015
• Last Verified: May 1, 2015

• Keywords provided by AstraZeneca: diabetes; exenatide once weekly; Byetta; glargine; Lantus; Amylin; Lilly
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine; Exenatide

Study Results

Participant Flow

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Period Title: Overall Study
STARTED	215	212
COMPLETED	193	201
NOT COMPLETED	22	11

Baseline Characteristics

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine	Total
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day	Total of all reporting groups
Overall Participants	215	212	427
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	160 74.4%	156 73.6%	316 74%
>=65 years	55 25.6%	56 26.4%	111 26%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.1 (10.44)	56.4 (11.16)	56.8 (10.80)
Sex: Female, Male (Count of Participants)
Female	73 34%	64 30.2%	137 32.1%
Male	142 66%	148 69.8%	290 67.9%
Glycosylated hemoglobin (HbA1c) (percentage of total hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of total hemoglobin]	8.51 (0.823)	8.50 (0.791)	8.50 (0.806)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	69.95 (13.246)	71.03 (13.932)	70.49 (13.586)
Background Oral Antidiabetic Agent (OAD) (participants) [Number]
Biguanide (BG)	145 67.4%	142 67%	287 67.2%
BG+Thiazolidine Derivative (TZD)	70 32.6%	70 33%	140 32.8%

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to Endpoint (Week 26)
Description	Change in HbA1c from baseline to endpoint (Week 26).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Statistical analysis of this study was performed for the full analysis set (FAS). FAS consisted of randomized patients who received administration of the study drug at least once and had measurement values after administration. Missing data at endpoint was imputed using last observation carried forward (LOCF) approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	214	212
Least Squares Mean (Standard Error) [percentage of total hemoglobin]	-1.11 (0.06)	-0.68 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	The expected changes in HbA1c from baseline were considered to be the same between the groups, and the common standard deviation assumed to be 1.2%. Assuming a type I error of 0.025 (one-sided), a power of 0.9 and a noninferiority margin of 0.4%, 191 subjects per group would be necessary to confirm the noninferiority by the two-sample t-test. When the proportion of the subjects missing post-baseline data was assumed to be 10%, the target number of subjects were 420 in total (210 subjects/group).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Noninferiority of exenatide QW to insulin glargine with respect to change in HbA1c was to be concluded if the upper limit of the 95% confidence interval (CI) for the treatment difference was less than 0.4%. Change in HbA1c from baseline to endpoint was analyzed using a LOCF ANCOVA model with treatment, baseline HbA1c stratum (<8.5%, >=8.5%), background OAD, and presence/absence of pretreatment with SU as factors and baseline HbA1c as a covariate.
Statistical Test of Hypothesis	p-Value	<.001
	Comments	No adjustments for multiplicity will be performed
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -0.59 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Subjects Achieving HbA1c<=7%
Description	Percentage of subjects achieving HbA1c <=7.0% (for subjects with HbA1c >7% at baseline)
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Only subjects with baseline HbA1c > target were included in calculation. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	211	210
Number [percentage of subjects]	42.2	21.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	Percentage of subjects achieving HbA1c<=7% at endpoint were compared between treatments using a Cochran-Mantel-Haenszel (CMH) test, in which background OAD and presence/absence of pretreatment with SU served as the stratification factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Percentage of Subjects Achieving HbA1c<=6.5%
Description	Percentage of subjects achieving HbA1c <=6.5% (for subjects with HbA1c >6.5% at baseline)
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Only subjects with baseline HbA1c > target were included in calculation. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	214	212
Number [percentage of subjects]	20.6	4.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	Percentage of subjects achieving HbA1c<=6.5% at endpoint were compared between treatments using a CMH test, in which background OAD and presence/absence of pretreatment with SU served as the stratification factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Change in Fasting Serum Glucose (FSG) From Baseline to Endpoint (Week 26)
Description	Change in FSG (centralized measurement) from baseline to endpoint (Week 26)
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	212	211
Least Squares Mean (Standard Error) [mg/dL]	-46.09 (2.40)	-40.82 (2.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	Change in FSG from baseline to endpoint was analyzed using a LOCF ANCOVA model with treatment, background OAD, and presence/absence of pretreatment with SU as factors and baseline FSG as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.103
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-5.28
	Confidence Interval	(2-Sided) 95%; -11.62 to 1.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.23
	Estimation Comments

5. Secondary Outcome

Title	Change in Body Weight From Baseline to Endpoint (Week 26)
Description	Change in Body Weight from baseline to endpoint (Week 26)
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	214	212
Least Squares Mean (Standard Error) [kg]	-1.67 (0.17)	0.34 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	Change in body weight from baseline to endpoint was analyzed using a LOCF ANCOVA model with treatment, background OAD, and presence/absence of pretreatment with SU as factors and baseline body weight as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.01
	Confidence Interval	(2-Sided) 95%; -2.46 to -1.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.23
	Estimation Comments

6. Secondary Outcome

Title	Change in Total Cholesterol From Baseline to Endpoint (Week 26)
Description	Change in Total Cholesterol from baseline to endpoint (Week 26)
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	213	212
Least Squares Mean (Standard Error) [mg/dL]	-14.21 (1.67)	-6.32 (1.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	Change in total cholesterol from baseline to endpoint was analyzed using a LOCF ANCOVA model with treatment, background OAD, and presence/absence of pretreatment with SU as factors and baseline total cholesterol as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.89
	Confidence Interval	(2-Sided) 95%; -12.33 to -3.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.26
	Estimation Comments

7. Secondary Outcome

Title	Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Endpoint (Week 26)
Description	Change in HDL-C from baseline to endpoint (Week 26)
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	213	212
Least Squares Mean (Standard Error) [mg/dL]	-0.99 (0.52)	-0.71 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	Change in HDL-C from baseline to endpoint was analyzed using a LOCF ANCOVA model with treatment, background OAD, and presence/absence of pre-treatment with SU as factors and baseline HDL-C as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.689
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -1.64 to 1.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.69
	Estimation Comments

8. Secondary Outcome

Title	Ratio of Fasting Triglycerides at Endpoint (Week 26) to Baseline
Description	Ratio of Triglycerides (measured in mg/dL) at endpoint (Week 26) to Baseline. Log(Postbaseline Triglycerides) - log(Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	213	212
Least Squares Mean (Standard Error) [ratio]	1.00 (1.02)	1.00 (1.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide Once Weekly, Insulin Glargine
	Comments	Triglycerides data were logarithm-transformed and the change at endpoint to baseline, expressed as the ratio, was analyzed using a LOCF ANCOVA model with treatment, background OAD, and presence/absence of pretreatment with SU as factors and baseline triglycerides as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.990
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Geometric Least Squares Mean Ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.03
	Estimation Comments

9. Secondary Outcome

Title	Change in Blood Pressure From Baseline to Endpoint (Week 26)
Description	Change in Blood Pressure from baseline to endpoint (Week 26)
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS Population. Missing data at endpoint was imputed using LOCF approach.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	214	212
Systolic Blood Pressure	-4.5 (14.04)	-2.6 (14.29)
Diastolic Blood Pressure	-1.1 (9.25)	-2.5 (8.88)

10. Secondary Outcome

Title	Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
Description	Major confirmed hypoglycemia was defined as (1) any event accompanying symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure but resolved promptly in response to administration of glucagon or (2) glucose, or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) requiring assistance because of severe impairment in consciousness or motor activity whether or not symptoms of hypoglycemia were felt by the patient. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

FAS Population.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	215	212
Mean (Standard Error) [events per subject-year]	0.00 (0.00)	0.00 (0.00)

11. Secondary Outcome

Title	Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events
Description	Minor confirmed hypoglycemia was defined as any event a patient felt that he or she was experiencing a sign or symptom associated with hypoglycemia that resolved by self-treatment or on its own, and a concurrent self-monitoring fingerstick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

FAS Population.

Arm/Group Title	Exenatide Once Weekly	Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.	Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
Measure Participants	215	212
Mean (Standard Error) [events per subject-year]	0.01 (0.01)	0.16 (0.13)

Adverse Events

Arm/Group Title	Exenatide Once Weekly		Insulin Glargine
Arm/Group Description	Subcutaneous injection, 2.0mg, once a week.		Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
All Cause Mortality
	Exenatide Once Weekly		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exenatide Once Weekly		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/215 (2.8%)		5/212 (2.4%)
Cardiac disorders
Atrial fibrillation	1/215 (0.5%)		0/212 (0%)
Cardiac failure	1/215 (0.5%)		0/212 (0%)
Gastrointestinal disorders
Diverticulitis intestinal haemorrhagic	0/215 (0%)		1/212 (0.5%)
Hepatobiliary disorders
Jaundice cholestatic	1/215 (0.5%)		0/212 (0%)
Cholecystitis	0/215 (0%)		1/212 (0.5%)
Cholecystitis acute	0/215 (0%)		1/212 (0.5%)
Injury, poisoning and procedural complications
Fibula fracture	1/215 (0.5%)		0/212 (0%)
Tibia fracture	1/215 (0.5%)		0/212 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/215 (0%)		1/212 (0.5%)
Hypoglycaemia	0/215 (0%)		1/212 (0.5%)
Nervous system disorders
Lacunar infarction	1/215 (0.5%)		0/212 (0%)
Respiratory, thoracic and mediastinal disorders
Status asthmaticus	1/215 (0.5%)		0/212 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide Once Weekly		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/215 (67.4%)		65/212 (30.7%)
Gastrointestinal disorders
Nausea	27/215 (12.6%)		6/212 (2.8%)
Constipation	24/215 (11.2%)		7/212 (3.3%)
Diarrhoea	19/215 (8.8%)		5/212 (2.4%)
Vomiting	18/215 (8.4%)		5/212 (2.4%)
Abdominal discomfort	11/215 (5.1%)		2/212 (0.9%)
General disorders
Injection site induration	58/215 (27%)		3/212 (1.4%)
Induration	18/215 (8.4%)		0/212 (0%)
Injection site pruritus	14/215 (6.5%)		0/212 (0%)
Infections and infestations
Nasopharyngitis	55/215 (25.6%)		45/212 (21.2%)
Metabolism and nutrition disorders
Decreased appetite	11/215 (5.1%)		1/212 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.