Safety and Efficacy Study of Exenatide Once Weekly in Adolescents With Type 2 Diabetes

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01554618
• Collaborator: (none)
• Enrollment: 84
• Locations: 35
• Arms: 2
• Actual Duration (Months): 113.1
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The study examines the Safety and efficacy study of exenatide once weekly in children and adolescents with type 2 diabetes

Condition or Disease	Intervention/Treatment	Phase
Children and Adolescent With Type 2 Diabetes	Drug: Exenatide Once Weekly; Drug: Placebo	Phase 3

Detailed Description

This Phase 3, double-blind (controlled assessment period), randomized, multicenter, placebo-controlled parallel study is designed to examine the efficacy and safety of EQW compared to placebo (PBO) in adolescents with type 2 diabetes for 24 weeks. This study will assess safety and efficacy of EQW (as monotherapy and adjunctive therapy to oral antidiabetic agents and/or insulin). At least 40% and not more than 60% of the randomized patients must be females. At least 40% of patients should be recruited from areas with similar ethnicity and lifestyle to those of the European Union member states. Long term safety and efficacy of EQW will subsequently be monitored for 28 weeks in the open-label, uncontrolled extension period (through Week 52). The study will be terminated at Visit 11 (Week 62/Study Termination) which will be a follow-up visit occurring 10 weeks after the last dose administration at Visit 10 (Week 52). This study will be conducted in 77 patients with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. During the controlled assessment period, approximately 77 patients will be randomly assigned in a 5:2 ratio to either EQW 2 mg (Group

1. or PBO (Group B), to yield at least 70 evaluable patients: at least 50 patients in the exenatide and at least 20 patients in the PBO group. Following the 24-week controlled assessment period, patients assigned to the EQW 2 mg treatment (Group A) will continue to be treated with EQW 2 mg during the extension period (through Week 52). Patients randomized to PBO (Group B) will receive EQW 2 mg beginning at the start of the extension period, Week 25 through Week 52. In addition to receiving study medications, all patients will participate in a lifestyle intervention program encompassing diet and physical activity modifications following the signing of the informed consent and assent forms (Visit 1 [Week -2]) through the end of the extension period (Week 52). Following Visit 11 (Week 62/Study Termination), patients whose height increase is at least 5 mm between Visit 8 (Week 28) and Visit 11 (Week 62/Study Termination) will participate in a long-term safety follow-up period. Patients who discontinue study medication prior to Visit 11 (Week 62/Study Termination) will also participate in the Extended Safety Follow-up Period, unless they have a height increase of less than 5 mm over a 6-month interval at study site visits prior to discontinuation of study medication. Patients who do not have height assessments at study-site visits over a 6-month interval prior to discontinuation of study medication will enter the Extended Safety Follow-up Period. The Extended Safety Follow Up Period will continue for up to 3 years or until the difference between two 6-month interval visits is less than a 5 mm increase (whichever comes first). No study medication will be administered during the Extended Safety Follow-up Period. Blood samples will be collected for calcitonin and carcinoembryonic antigen (CEA) laboratory measurements.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Double-Blind, Placebo-Controlled, Randomized, Multi-Center Study to Assess the Safety and Efficacy of Exenatide Once Weekly in Adolescents With Type 2 Diabetes
• Actual Study Start Date: Dec 2, 2011
• Actual Primary Completion Date: May 6, 2020
• Actual Study Completion Date: May 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EQW Exenatide once weekly	Drug: Exenatide Once Weekly; 2 mg exenatide once weekly; Other Names: BYDUREON
Placebo Comparator: Placebo Placebo once weekly	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period) [Baseline (Week 0) and Week 24]

   Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication.

2. Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) [Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up]

   A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs [SAEs] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication.

3. Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 [Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24]

   Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers < 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication.

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period) [Baseline (Week 0) and Week 24]

   Change from baseline in FPG to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.

2. Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period) [Baseline (Week 0) and Week 24]

   Change from baseline in body weight to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.

3. Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period) [Baseline (Week 0) and Week 24]

   Change from baseline in fasting insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.

4. Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) [At Week 24]

   The percentage of patients achieving HbA1c goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 during the controlled assessment period is reported. A Cochran-Mantel-Haenszel (CMH) analysis was performed with missing data treated as non-responder, and excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.

5. Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) [Baseline (Week 0) and Week 24]

   Change from baseline in lipid profiles to Week 24 during the controlled assessment period is reported as mean values (Standard International [SI] units). The following lipids were assessed: total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

6. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) [Baseline (Week 0) and Week 24]

   Change from baseline in SBP and DBP to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.

7. Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) [At Week 4, Week 8, Week 12, Week 18 and Week 24]

   Number of patients needing rescue medication at Week 24 and at each intermediate visit during the controlled assessment period is reported. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value > 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.

8. Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) [Baseline (Week 0) and Week 24]

   Change from baseline in HOMA-B and HOMA-S in patients who were not taking insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.

9. Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) [At Week 4, Week 8, Week 12, Week 18 and Week 24]

   Percentage of patients reporting injection site reactions at Week 24 and at each intermediate visit during the controlled assessment period is reported. Injection site reactions were presented from the AE case report form (CRF), based on the "Injection site reactions" higher level term. A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).

10. Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Baseline (Week 0) and Week 52]

    Change from baseline in HbA1c (%) to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

11. Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Baseline (Week 0) and Week 52]

    Change from baseline in FPG to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

12. Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Baseline (Week 0) and Week 52]

    Change from baseline in body weight to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

13. Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Baseline (Week 0) and Week 52]

    Change from baseline in fasting insulin to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

14. Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [At Week 52]

    The percentage of patients achieving HbA1c goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 52 among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

15. Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Baseline (Week 0) and Week 52]

    Change from baseline in lipid profiles to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values (SI units). The treatment period was defined as the controlled assessment period and extension period combined. The following lipids were assessed: total cholesterol, HDL-C, LDL-C, and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

16. Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Baseline (Week 0) and Week 52]

    Change from baseline in SBP and DBP to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

17. Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52]

    Number of patients needing rescue medication at Week 52 and at each intermediate visit during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value > 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.

18. Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Baseline (Week 0) and Week 52]

    Change from baseline in HOMA-B and HOMA-S to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.

19. Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52]

    Percentage of patients reporting injection site reactions at Week 52 and at each intermediate visit among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Injection site reactions were presented from the AE CRF, based on the "Injection site reactions" higher level term. An Extension Period AE was defined as an AE starting on or after day of first dose of open-label exenatide to last dose + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).

20. Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) [Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52]

    Geometric mean plasma exenatide concentrations up to Week 52 during the treatment period are reported (for the placebo then exenatide treatment group, only Weeks 24 and 52 were applicable). The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication were included. Data collected after discontinuation of study medication were excluded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Each patient must meet the following criteria to be enrolled in this study.

1. Is a child or an adolescent of 10 to <18 years old, at Visit 1 (Screening)

2. Has been diagnosed with type 2 diabetes mellitus per American Diabetes Association diagnostic criteria

3. HbA1c of 6.5% to 11.0%, inclusive, in patients not taking insulin/SU, and of 6.5% to 12.0%, inclusive, in patients taking insulin/SU, at Visit 1 (Screening)

4. Has a C-peptide of >0.6 ng/L at Visit 1 (Screening)

5. Has been treated with diet and exercise alone or in combination with a stable dose of an oral antidiabetic agent (e.g., metformin and/or SU) and/or insulin for their type 2 diabetes for at least 2 months prior to Visit 1 (Screening)

6. Has a fasting plasma glucose concentration <280 mg/dL (15.5 mmol/L) at Visit 1 (Screening)

Patients who meet any of the following criteria will be excluded from the study.

1. Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the Investigator, including but not limited to the following conditions:

2. Hepatic disease (defined by aspartate or alanine transaminase >3.0 times the upper limit of normal (ULN)

3. Renal disease or serum creatinine >1.5 mg/dL (132.6 µmol/L) (males) or 1.4 mg/dL (123.8 µmol/L) (females)

4. Gastrointestinal disease deemed significant by the Investigator

5. Organ transplantation

6. Chronic infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus)

7. Clinically significant malignant disease (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1 (Screening)

8. Has positive antibody titers to glutamic acid decarboxylase (GAD65) or islet cell antigen (ICA512) at Visit 1 (Screening)

9. Has a personal or family history of elevated calcitonin, calcitonin >100 ng/L, medullary thyroid carcinoma, or multiple endocrine neoplasia-2

10. Has ever used exenatide (exenatide once weekly [exenatide LAR], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., liraglutide [Victoza®])

11. Is pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90078
2	Research Site	New Haven	Connecticut	United States	06511
3	Research Site	Iowa City	Iowa	United States	52242
4	Research Site	Kansas City	Kansas	United States	64111
5	Research Site	Louisville	Kentucky	United States	40202
6	Research Site	Boston	Massachusetts	United States	02115
7	Research Site	Jackson	Mississippi	United States	39216-4505
8	Research Site	Buffalo	New York	United States	14222
9	Research Site	Chapel Hill	North Carolina	United States	27599
10	Research Site	Charlotte	North Carolina	United States	28205
11	Research Site	Cleveland	Ohio	United States	44106
12	Research Site	Oklahoma City	Oklahoma	United States	73104
13	Research Site	Rapid City	South Dakota	United States	57701
14	Research Site	Nashville	Tennessee	United States	37232
15	Research Site	Dallas	Texas	United States	75390
16	Research Site	Houston	Texas	United States	77030
17	Research Site	Pleven		Bulgaria	5800
18	Research Site	Sevlievo		Bulgaria	5400
19	Research Site	Baja		Hungary	6500
20	Research Site	Budapest		Hungary	1023
21	Research Site	Budapest		Hungary	1083
22	Research Site	Budapest		Hungary	1094
23	Research Site	Szeged		Hungary	6725
24	Research Site	Beer Sheva		Israel	84101
25	Research Site	Haifa		Israel	31096
26	Research Site	Ramat Gan		Israel	5265601
27	Research Site	Kuwait City		Kuwait	1180
28	Research Site	Aguascalientes		Mexico	20016
29	Research Site	Durango		Mexico	34000
30	Research Site	Guadalajara		Mexico	44130
31	Research Site	Veracruz		Mexico	91910
32	Research Site	Chernivts?		Ukraine	58001
33	Research Site	Ivano-Frankivsk		Ukraine	76014
34	Research Site	Kharkiv Region		Ukraine	61002
35	Research Site	Odesa		Ukraine	65031

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 14, 2017
• Statistical Analysis Plan - May 21, 2020

More Information

Additional Information:

• redacted SAP
• redacted CSP
• CSR Synopsis

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01554618
• Other Study ID Numbers: D5551C00002
• First Posted: Mar 15, 2012
• Last Update Posted: Nov 30, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by AstraZeneca: exenatide; type 2 diabetes; GLP-1 receptor agonist
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Exenatide

Study Results

Participant Flow

Recruitment Details	This study was conducted in adolescents (aged 10 to 17 years inclusive) with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. 27 study centers in 6 countries randomized patients during the study.
Pre-assignment Detail	Study had a screening period (5 weeks), controlled assessment period (24 weeks; patients randomized 5:2 to exenatide or placebo), open-label extension period (28 weeks) and post-treatment follow-up period (10 weeks). 84 patients were randomized but 1 due to clinical error and immediately discontinued, thus, 83 patients were included in the study.

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Controlled assessment Period: Patients received exenatide 2 milligrams (mg) subcutaneous (SC) injection once weekly for 24 weeks. Extension period: Patients continued to receive exenatide 2 mg SC once weekly during the open-label extension period for 28 weeks (through Week 52).	Controlled assessment period: Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks. Extension period: Patients then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Period Title: Randomized Through Start of Treatment
STARTED	59	24
COMPLETED	58	24
NOT COMPLETED	1	0
Period Title: Randomized Through Start of Treatment
STARTED	58	24
COMPLETED	50	23
NOT COMPLETED	8	1
Period Title: Randomized Through Start of Treatment
STARTED	49	23
COMPLETED	46	18
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Exenatide	Placebo	Total
Arm/Group Description	Controlled assessment period: Patients received exenatide 2 mg SC injection once weekly for 24 weeks. Extension period: Patients continued to receive exenatide 2 mg SC once weekly during the open-label extension period for 28 weeks (through Week 52).	Controlled assessment period: Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks. Extension period: Patients then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).	Total of all reporting groups
Overall Participants	58	24	82
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.9 (1.88)	15.6 (1.66)	15.1 (1.84)
Age, Customized (Count of Participants)
< 10	0 0%	0 0%	0 0%
≥ 10 to ≤ 12	8 13.8%	3 12.5%	11 13.4%
≥ 13 to ≤ 16	36 62.1%	12 50%	48 58.5%
> 16	14 24.1%	9 37.5%	23 28%
Sex: Female, Male (Count of Participants)
Female	31 53.4%	17 70.8%	48 58.5%
Male	27 46.6%	7 29.2%	34 41.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	25 43.1%	8 33.3%	33 40.2%
Not Hispanic or Latino	29 50%	13 54.2%	42 51.2%
Unknown or Not Reported	4 6.9%	3 12.5%	7 8.5%
Race/Ethnicity, Customized (Count of Participants)
White	23 39.7%	12 50%	35 42.7%
Black or African American	17 29.3%	8 33.3%	25 30.5%
Asian	2 3.4%	1 4.2%	3 3.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
American Indian or Alaska Native	4 6.9%	1 4.2%	5 6.1%
Other	12 20.7%	2 8.3%	14 17.1%
Region of Enrollment (Count of Participants)
Bulgaria	1 1.7%	0 0%	1 1.2%
Hungary	3 5.2%	1 4.2%	4 4.9%
Israel	4 6.9%	3 12.5%	7 8.5%
Mexico	13 22.4%	2 8.3%	15 18.3%
United States	35 60.3%	17 70.8%	52 63.4%
Kuwait	2 3.4%	1 4.2%	3 3.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)
Description	Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	58	24
Least Squares Mean (Standard Error) [percentage (% HbA1c)]	-0.36 (0.184)	0.49 (0.273)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline HbA1c value (continuous) and baseline HbA1c by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95%; -1.51 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.330
	Estimation Comments	Exenatide versus Placebo

2. Primary Outcome

Title	Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)
Description	A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs [SAEs] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication.
Time Frame	Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. One patient who was randomized to placebo received a dose of exenatide in error and was subsequently reassigned to the exenatide treatment group for analyses based on actual treatment.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	59	23
Any AE	61.0 105.2%	73.9 307.9%
Any AE with outcome of death	0 0%	0 0%
Any SAE	3.4 5.9%	4.3 17.9%
Any AE leading to discontinuation of treatment	0 0%	0 0%
Any AE leading to discontinuation from study	0 0%	0 0%
Any AE related to treatment	25.4 43.8%	21.7 90.4%

3. Primary Outcome

Title	Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24
Description	Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers < 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication.
Time Frame	Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients receiving exenatide in the controlled assessment period were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).
Measure Participants	59
Week 4: High Positive	17.0 29.3%
Week 4: Low Positive	30.2 52.1%
Week 4: Treatment-Emergent ADA Positive	45.3 78.1%
Week 8: High Positive	53.8 92.8%
Week 8: Low Positive	38.5 66.4%
Week 8: Treatment-Emergent ADA Positive	92.3 159.1%
Week 12: High Positive	60.0 103.4%
Week 12: Low Positive	38.0 65.5%
Week 12: Treatment-Emergent ADA Positive	98.0 169%
Week 24: High Positive	40.8 70.3%
Week 24: Low Positive	55.1 95%
Week 24: Treatment-Emergent ADA Positive	95.9 165.3%

4. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)
Description	Change from baseline in FPG to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	58	24
Least Squares Mean (Standard Error) [milligrams per deciliter (mg/dL)]	-5.2 (7.65)	16.5 (11.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline fasting plasma glucose value, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline fasting plasma glucose by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.119
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-21.6
	Confidence Interval	(2-Sided) 95%; -49.0 to 5.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 13.70
	Estimation Comments	Exenatide versus Placebo

5. Secondary Outcome

Title	Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period)
Description	Change from baseline in body weight to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	58	24
Least Squares Mean (Standard Error) [kilogram (kg)]	-0.59 (0.665)	0.63 (0.982)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline body weight, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline body weight by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.307
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.22
	Confidence Interval	(2-Sided) 95%; -3.59 to 1.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.189
	Estimation Comments	Exenatide versus Placebo

6. Secondary Outcome

Title	Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)
Description	Change from baseline in fasting insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	58	24
Least Squares Mean (Standard Error) [picomoles per liter (pmol/L)]	79.6 (52.28)	-15.3 (78.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline fasting insulin, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline fasting insulin by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.323
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	94.9
	Confidence Interval	(2-Sided) 95%; -95.6 to 285.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 95.26
	Estimation Comments	Exenatide versus Placebo

7. Secondary Outcome

Title	Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)
Description	The percentage of patients achieving HbA1c goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 during the controlled assessment period is reported. A Cochran-Mantel-Haenszel (CMH) analysis was performed with missing data treated as non-responder, and excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	At Week 24

Outcome Measure Data

Analysis Population Description

The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients with data available were included in the analysis.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	48	22
HbA1c <6 .5%	19.0 32.8%	4.2 17.5%
HbA1c ≤ 6.5%	19.0 32.8%	4.2 17.5%
HbA1c < 7.0%	31.0 53.4%	8.3 34.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Treatment difference in HbA1c < 6.5%: Treatment group comparison was based on CMH test stratified by screening HbA1c (<9.0% or >=9.0%). P-value was from the general association statistic.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	14.8
	Confidence Interval	(2-Sided) 95%; 1.9 to 27.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exenatide versus Placebo. Difference was the risk difference of the 2 proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Treatment difference in HbA1c ≤ 6.5%: Treatment group comparison was based on CMH test stratified by screening HbA1c (<9.0% or >=9.0%). P-value was from the general association statistic.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	14.8
	Confidence Interval	(2-Sided) 95%; 1.9 to 27.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exenatide versus Placebo. Difference was the risk difference of the 2 proportions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Treatment difference in HbA1c < 7.0%: Treatment group comparison was based on CMH test stratified by screening HbA1c (<9.0% or >=9.0%). P-value was from the general association statistic.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	22.7
	Confidence Interval	(2-Sided) 95%; 6.5 to 39.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exenatide versus Placebo. Difference was the risk difference of the 2 proportions.

8. Secondary Outcome

Title	Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period)
Description	Change from baseline in lipid profiles to Week 24 during the controlled assessment period is reported as mean values (Standard International [SI] units). The following lipids were assessed: total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with data available were included in the analysis.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	58	24
Total Cholesterol	-0.117 (0.7124)	-0.114 (0.5819)
HDL-C	-0.035 (0.1950)	-0.047 (0.1039)
LDL-C	-0.050 (0.5618)	-0.110 (0.5983)
Triglycerides	-0.122 (1.0303)	0.094 (0.6626)

9. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period)
Description	Change from baseline in SBP and DBP to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	58	24
SBP	-0.7 (1.48)	2.2 (2.15)
DBP	0.2 (1.00)	-1.3 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Treatment difference in SBP: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline SBP, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline SBP by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.284
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -8.0 to 2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.61
	Estimation Comments	Exenatide versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Treatment difference in DBP: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline DBP, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline DBP by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.376
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -2.0 to 5.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.77
	Estimation Comments	Exenatide versus Placebo

10. Secondary Outcome

Title	Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period)
Description	Number of patients needing rescue medication at Week 24 and at each intermediate visit during the controlled assessment period is reported. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value > 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time Frame	At Week 4, Week 8, Week 12, Week 18 and Week 24

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with data available at each specified visit were included in the analysis.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	58	24
Week 4	0 0%	0 0%
Week 8	0 0%	0 0%
Week 12	0 0%	0 0%
Week 18	1 1.7%	0 0%
Week 24	0 0%	0 0%

11. Secondary Outcome

Title	Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period)
Description	Change from baseline in HOMA-B and HOMA-S in patients who were not taking insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Homeostasis model assessments were only performed in patients who were not taking insulin.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	14	7
HOMA-B	63.98 (39.552)	-26.39 (56.138)
HOMA-S	0.62 (3.607)	7.37 (4.914)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Treatment difference in HOMA-B: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline HOMA-B, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline HOMA-B by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.211
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	90.37
	Confidence Interval	(2-Sided) 95%; -57.27 to 238.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 69.207
	Estimation Comments	Exenatide versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Controlled Assessment Period - Placebo
	Comments	Treatment difference in HOMA-S: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline HOMA-S, screening HbA1c (< 9.0% or ≥ 9.0%), and baseline HOMA-S by visit interaction as fixed effects, using an unstructured covariance matrix.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.289
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.75
	Confidence Interval	(2-Sided) 95%; -19.80 to 6.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.173
	Estimation Comments	Exenatide versus Placebo

12. Secondary Outcome

Title	Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period)
Description	Percentage of patients reporting injection site reactions at Week 24 and at each intermediate visit during the controlled assessment period is reported. Injection site reactions were presented from the AE case report form (CRF), based on the "Injection site reactions" higher level term. A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time Frame	At Week 4, Week 8, Week 12, Week 18 and Week 24

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients with data available at each specified visit were included in the analysis.

Arm/Group Title	Controlled Assessment Period - Exenatide	Controlled Assessment Period - Placebo
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Measure Participants	59	23
Week 4	8.5 14.7%	8.7 36.3%
Week 8	3.5 6%	4.3 17.9%
Week 12	1.9 3.3%	0 0%
Week 18	0 0%	0 0%
Week 24	0 0%	0 0%

13. Secondary Outcome

Title	Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Change from baseline in HbA1c (%) to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52

Outcome Measure Data

Analysis Population Description

The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	39	17
Mean (Standard Deviation) [percentage (% HbA1c)]	-0.10 (1.711)	0.53 (2.123)

14. Secondary Outcome

Title	Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Change from baseline in FPG to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	38	16
Mean (Standard Deviation) [mg/dL]	-1.8 (62.64)	10.6 (75.49)

15. Secondary Outcome

Title	Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Change from baseline in body weight to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	39	18
Mean (Standard Deviation) [kg]	0.04 (6.088)	-0.04 (4.687)

16. Secondary Outcome

Title	Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Change from baseline in fasting insulin to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	37	16
Mean (Standard Deviation) [pmol/L]	-32.4 (273.57)	121.5 (379.13)

17. Secondary Outcome

Title	Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	The percentage of patients achieving HbA1c goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 52 among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	At Week 52

Outcome Measure Data

Analysis Population Description

The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients who received open-label exenatide and with data available were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	39	17
HbA1c < 6.5%	30.8 53.1%	23.5 97.9%
HbA1c ≤ 6.5%	30.8 53.1%	23.5 97.9%
HbA1c < 7.0%	35.9 61.9%	29.4 122.5%

18. Secondary Outcome

Title	Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Change from baseline in lipid profiles to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values (SI units). The treatment period was defined as the controlled assessment period and extension period combined. The following lipids were assessed: total cholesterol, HDL-C, LDL-C, and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	37	15
Total Cholesterol	-0.188 (0.4199)	-0.255 (0.9075)
HDL-C	0.004 (0.1740)	-0.076 (0.2327)
LDL-C	-0.175 (0.4025)	-0.152 (0.7682)
Triglycerides	-0.155 (1.1108)	-0.043 (0.5971)

19. Secondary Outcome

Title	Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Change from baseline in SBP and DBP to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	39	18
SBP	-0.7 (13.09)	-0.6 (8.73)
DBP	1.1 (8.65)	-2.5 (10.65)

20. Secondary Outcome

Title	Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Number of patients needing rescue medication at Week 52 and at each intermediate visit during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value > 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time Frame	At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients who received open-label exenatide and with data available were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	49	23
Week 4	0 0%	0 0%
Week 8	0 0%	0 0%
Week 12	0 0%	0 0%
Week 18	1 1.7%	0 0%
Week 24	0 0%	0 0%
Week 28	2 3.4%	1 4.2%
Week 40	2 3.4%	0 0%
Week 52	0 0%	0 0%

21. Secondary Outcome

Title	Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Change from baseline in HOMA-B and HOMA-S to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time Frame	Baseline (Week 0) and Week 52

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	8	5
HOMA-B	-2.58 (130.435)	42.02 (183.869)
HOMA-S	9.85 (12.366)	2.36 (7.631)

22. Secondary Outcome

Title	Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Percentage of patients reporting injection site reactions at Week 52 and at each intermediate visit among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Injection site reactions were presented from the AE CRF, based on the "Injection site reactions" higher level term. An Extension Period AE was defined as an AE starting on or after day of first dose of open-label exenatide to last dose + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time Frame	At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients with data available at each specified visit were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	50	22
Week 4	10.0 17.2%	9.1 37.9%
Week 8	4.0 6.9%	4.5 18.8%
Week 12	2.0 3.4%	0 0%
Week 18	0 0%	0 0%
Week 24	0 0%	0 0%
Week 28	4.0 6.9%	0 0%
Week 40	0 0%	0 0%
Week 52	0 0%	0 0%

23. Secondary Outcome

Title	Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Description	Geometric mean plasma exenatide concentrations up to Week 52 during the treatment period are reported (for the placebo then exenatide treatment group, only Weeks 24 and 52 were applicable). The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication were included. Data collected after discontinuation of study medication were excluded.
Time Frame	Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic (PK) Analysis Set consisted of all patients who received at least 1 dose of exenatide, for whom any postdose data were available and who did not deviate from the protocol in ways that would significantly affect the PK analyses. Only patients who received open-label exenatide and with data available were included in the analysis.

Arm/Group Title	Treatment Period - Exenatide	Treatment Period - Placebo Then Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period and continued to receive exenatide 2 mg SC once weekly during the open-label extension period for a further 28 weeks (from Week 0 to Week 52 overall).	Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period and then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52).
Measure Participants	55	19
Baseline	NA (NA)
Week 4	41.51 (91.9)
Week 8	130.60 (83.8)
Week 12	163.58 (92.3)
Week 24	140.81 (84.0)	NA (NA)
Week 52	88.88 (79.2)	105.56 (154.9)

Adverse Events

Time Frame	After the first dose of study medication in period through the end of the treatment in period + 90 days for SAEs (or + 7 days for non-serious (i.e. Other) AEs. Overall time frame: up to maximum of approximately 37 weeks and 41 weeks for controlled assessment period and extension period, respectively.
Adverse Event Reporting Description	The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. One patient who was randomized to placebo received a dose of exenatide in error and was subsequently reassigned to the exenatide treatment group for analyses based on actual treatment (ie, for analyses based on the Safety Analysis Set).
Arm/Group Title	Controlled Assessment Period - Exenatide		Controlled Assessment Period - Placebo		Extension Period - Exenatide		Extension Period - Placebo to Exenatide
Arm/Group Description	Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.		Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.		Patients received open-label exenatide 2 mg SC injection once weekly for 28 weeks during the extension period. Patients in this treatment group had previously received exenatide during the controlled assessment period.		Patients received open-label exenatide 2 mg SC injection once weekly for 28 weeks during the extension period. Patients in this treatment group had previously received placebo during the controlled assessment period.
All Cause Mortality
	Controlled Assessment Period - Exenatide		Controlled Assessment Period - Placebo		Extension Period - Exenatide		Extension Period - Placebo to Exenatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/23 (0%)		0/50 (0%)		0/22 (0%)
Serious Adverse Events
	Controlled Assessment Period - Exenatide		Controlled Assessment Period - Placebo		Extension Period - Exenatide		Extension Period - Placebo to Exenatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/59 (3.4%)		1/23 (4.3%)		3/50 (6%)		1/22 (4.5%)
Gastrointestinal disorders
Gastritis	0/59 (0%)	0	0/23 (0%)	0	1/50 (2%)	1	0/22 (0%)	0
Irritable bowel syndrome	0/59 (0%)	0	1/23 (4.3%)	1	0/50 (0%)	0	0/22 (0%)	0
Infections and infestations
Abscess limb	1/59 (1.7%)	1	0/23 (0%)	0	0/50 (0%)	0	0/22 (0%)	0
Cellulitis	0/59 (0%)	0	0/23 (0%)	0	1/50 (2%)	1	0/22 (0%)	0
Pneumonia	0/59 (0%)	0	0/23 (0%)	0	1/50 (2%)	1	0/22 (0%)	0
Psychiatric disorders
Major depression	1/59 (1.7%)	1	0/23 (0%)	0	0/50 (0%)	0	0/22 (0%)	0
Suicidal ideation	0/59 (0%)	0	0/23 (0%)	0	1/50 (2%)	1	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Controlled Assessment Period - Exenatide		Controlled Assessment Period - Placebo		Extension Period - Exenatide		Extension Period - Placebo to Exenatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/59 (42.4%)		10/23 (43.5%)		10/50 (20%)		4/22 (18.2%)
Gastrointestinal disorders
Abdominal pain	2/59 (3.4%)	5	3/23 (13%)	3	1/50 (2%)	1	0/22 (0%)	0
Abdominal pain upper	3/59 (5.1%)	3	0/23 (0%)	0	1/50 (2%)	1	0/22 (0%)	0
Diarrhoea	5/59 (8.5%)	5	1/23 (4.3%)	1	1/50 (2%)	1	0/22 (0%)	0
Nausea	4/59 (6.8%)	4	1/23 (4.3%)	1	0/50 (0%)	0	1/22 (4.5%)	1
Vomiting	3/59 (5.1%)	3	0/23 (0%)	0	2/50 (4%)	2	0/22 (0%)	0
General disorders
Injection site erythema	3/59 (5.1%)	3	1/23 (4.3%)	1	0/50 (0%)	0	0/22 (0%)	0
Infections and infestations
Nasopharyngitis	4/59 (6.8%)	5	2/23 (8.7%)	3	1/50 (2%)	1	1/22 (4.5%)	2
Upper respiratory tract infection	6/59 (10.2%)	6	0/23 (0%)	0	2/50 (4%)	2	0/22 (0%)	0
Urinary tract infection	3/59 (5.1%)	4	2/23 (8.7%)	2	0/50 (0%)	0	0/22 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	1/59 (1.7%)	2	1/23 (4.3%)	1	0/50 (0%)	0	2/22 (9.1%)	2
Hypoglycaemia	3/59 (5.1%)	4	0/23 (0%)	0	1/50 (2%)	2	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	3/59 (5.1%)	3	0/23 (0%)	0	0/50 (0%)	0	0/22 (0%)	0
Nervous system disorders
Headache	4/59 (6.8%)	5	2/23 (8.7%)	3	2/50 (4%)	2	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	4/59 (6.8%)	5	1/23 (4.3%)	1	0/50 (0%)	0	2/22 (9.1%)	3

Limitations/Caveats

For statistical analyses of change from baseline in HOMA-B and HOMA-S, due to the limited sample size (n=14 and n=7 in the extenatide and placebo groups, respectively) it is difficult to accurately interpret these data. The study design included an extended safety follow-up period which continued for up to 3 years or until the increase in height between two 6-month interval visits was <5 mm (whichever came first). No study medication was administered during the extended safety follow-up period.

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.