Trial Outcomes & Findings for Safety and Efficacy Study of Exenatide Once Weekly in Adolescents With Type 2 Diabetes (NCT NCT01554618)

NCT ID: NCT01554618

Last Updated: 2021-11-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 84 participants
• Primary outcome timeframe: Baseline (Week 0) and Week 24
• Results posted on: 2021-11-30

Participant Flow

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.

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.

Participant milestones

Measure	Exenatide 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).	Placebo 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).
Randomized Through Start of Treatment STARTED	59	24
Randomized Through Start of Treatment COMPLETED	58	24
Randomized Through Start of Treatment NOT COMPLETED	1	0
Controlled Assessment Period STARTED	58	24
Controlled Assessment Period COMPLETED	50	23
Controlled Assessment Period NOT COMPLETED	8	1
Open-Label Extension Period STARTED	49	23
Open-Label Extension Period COMPLETED	46	18
Open-Label Extension Period NOT COMPLETED	3	5

Reasons for withdrawal

Measure	Exenatide 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).	Placebo 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).
Randomized Through Start of Treatment Adverse Event	1	0
Controlled Assessment Period Lost to Follow-up	2	1
Controlled Assessment Period Withdrawal by Subject	6	0
Open-Label Extension Period Withdrawal by Subject	2	3
Open-Label Extension Period Physician Decision	0	1
Open-Label Extension Period Lost to Follow-up	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Exenatide n=58 Participants 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).	Placebo n=24 Participants 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 n=82 Participants Total of all reporting groups
Age, Continuous	14.9 years STANDARD_DEVIATION 1.88 • n=5 Participants	15.6 years STANDARD_DEVIATION 1.66 • n=7 Participants	15.1 years STANDARD_DEVIATION 1.84 • n=5 Participants
Age, Customized < 10	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized ≥ 10 to ≤ 12	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Age, Customized ≥ 13 to ≤ 16	36 Participants n=5 Participants	12 Participants n=7 Participants	48 Participants n=5 Participants
Age, Customized > 16	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	17 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	7 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	8 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	13 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White	23 Participants n=5 Participants	12 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	17 Participants n=5 Participants	8 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Other	12 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Bulgaria	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Hungary	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Israel	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Mexico	13 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	35 Participants n=5 Participants	17 Participants n=7 Participants	52 Participants n=5 Participants
Region of Enrollment Kuwait	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=58 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=24 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)	-0.36 percentage (% HbA1c) Standard Error 0.184	0.49 percentage (% HbA1c) Standard Error 0.273

PRIMARY outcome

Timeframe: Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=59 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=23 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) Any AE	61.0 percentage of participants	73.9 percentage of participants
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) Any AE with outcome of death	0 percentage of participants	0 percentage of participants
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) Any SAE	3.4 percentage of participants	4.3 percentage of participants
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) Any AE leading to discontinuation of treatment	0 percentage of participants	0 percentage of participants
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) Any AE leading to discontinuation from study	0 percentage of participants	0 percentage of participants
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) Any AE related to treatment	25.4 percentage of participants	21.7 percentage of participants

PRIMARY outcome

Timeframe: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=59 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 4: High Positive	17.0 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 4: Low Positive	30.2 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 4: Treatment-Emergent ADA Positive	45.3 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 8: High Positive	53.8 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 8: Low Positive	38.5 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 8: Treatment-Emergent ADA Positive	92.3 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 12: High Positive	60.0 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 12: Low Positive	38.0 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 12: Treatment-Emergent ADA Positive	98.0 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 24: High Positive	40.8 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 24: Low Positive	55.1 percentage of participants	—
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 Week 24: Treatment-Emergent ADA Positive	95.9 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

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

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=58 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=24 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)	-5.2 milligrams per deciliter (mg/dL) Standard Error 7.65	16.5 milligrams per deciliter (mg/dL) Standard Error 11.32

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

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

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=58 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=24 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period)	-0.59 kilogram (kg) Standard Error 0.665	0.63 kilogram (kg) Standard Error 0.982

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

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

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=58 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=24 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)	79.6 picomoles per liter (pmol/L) Standard Error 52.28	-15.3 picomoles per liter (pmol/L) Standard Error 78.49

SECONDARY outcome

Timeframe: At Week 24

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=48 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=22 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) HbA1c < 7.0%	31.0 percentage of participants Interval 19.1 to 42.9	8.3 percentage of participants Interval 0.0 to 19.4
Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) HbA1c <6 .5%	19.0 percentage of participants Interval 8.9 to 29.1	4.2 percentage of participants Interval 0.0 to 12.2
Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) HbA1c ≤ 6.5%	19.0 percentage of participants Interval 8.9 to 29.1	4.2 percentage of participants Interval 0.0 to 12.2

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=58 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=24 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) Total Cholesterol	-0.117 millimoles per liter (mmol/L) Standard Deviation 0.7124	-0.114 millimoles per liter (mmol/L) Standard Deviation 0.5819
Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) HDL-C	-0.035 millimoles per liter (mmol/L) Standard Deviation 0.1950	-0.047 millimoles per liter (mmol/L) Standard Deviation 0.1039
Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) LDL-C	-0.050 millimoles per liter (mmol/L) Standard Deviation 0.5618	-0.110 millimoles per liter (mmol/L) Standard Deviation 0.5983
Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) Triglycerides	-0.122 millimoles per liter (mmol/L) Standard Deviation 1.0303	0.094 millimoles per liter (mmol/L) Standard Deviation 0.6626

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

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

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=58 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=24 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) SBP	-0.7 millimeters mercury (mmHg) Standard Error 1.48	2.2 millimeters mercury (mmHg) Standard Error 2.15
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) DBP	0.2 millimeters mercury (mmHg) Standard Error 1.00	-1.3 millimeters mercury (mmHg) Standard Error 1.45

SECONDARY outcome

Timeframe: At Week 4, Week 8, Week 12, Week 18 and Week 24

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=58 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=24 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) Week 4	0 Participants	0 Participants
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) Week 8	0 Participants	0 Participants
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) Week 12	0 Participants	0 Participants
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) Week 18	1 Participants	0 Participants
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) Week 24	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=14 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=7 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) HOMA-B	63.98 percentage (%HOMA-B and %HOMA-S) Standard Error 39.552	-26.39 percentage (%HOMA-B and %HOMA-S) Standard Error 56.138
Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) HOMA-S	0.62 percentage (%HOMA-B and %HOMA-S) Standard Error 3.607	7.37 percentage (%HOMA-B and %HOMA-S) Standard Error 4.914

SECONDARY outcome

Timeframe: At Week 4, Week 8, Week 12, Week 18 and Week 24

Population: 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.

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).

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=59 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=23 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) Week 4	8.5 percentage of participants	8.7 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) Week 8	3.5 percentage of participants	4.3 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) Week 12	1.9 percentage of participants	0 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) Week 18	0 percentage of participants	0 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) Week 24	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=39 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=17 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)	-0.10 percentage (% HbA1c) Standard Deviation 1.711	0.53 percentage (% HbA1c) Standard Deviation 2.123

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=38 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=16 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)	-1.8 mg/dL Standard Deviation 62.64	10.6 mg/dL Standard Deviation 75.49

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=39 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=18 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)	0.04 kg Standard Deviation 6.088	-0.04 kg Standard Deviation 4.687

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=37 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=16 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)	-32.4 pmol/L Standard Deviation 273.57	121.5 pmol/L Standard Deviation 379.13

SECONDARY outcome

Timeframe: At Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=39 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=17 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
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) HbA1c < 6.5%	30.8 percentage of participants	23.5 percentage of participants
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) HbA1c ≤ 6.5%	30.8 percentage of participants	23.5 percentage of participants
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) HbA1c < 7.0%	35.9 percentage of participants	29.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=37 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=15 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Total Cholesterol	-0.188 mmol/L Standard Deviation 0.4199	-0.255 mmol/L Standard Deviation 0.9075
Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) HDL-C	0.004 mmol/L Standard Deviation 0.1740	-0.076 mmol/L Standard Deviation 0.2327
Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) LDL-C	-0.175 mmol/L Standard Deviation 0.4025	-0.152 mmol/L Standard Deviation 0.7682
Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Triglycerides	-0.155 mmol/L Standard Deviation 1.1108	-0.043 mmol/L Standard Deviation 0.5971

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=39 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=18 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) DBP	1.1 mmHg Standard Deviation 8.65	-2.5 mmHg Standard Deviation 10.65
Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) SBP	-0.7 mmHg Standard Deviation 13.09	-0.6 mmHg Standard Deviation 8.73

SECONDARY outcome

Timeframe: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=49 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=23 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
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) Week 4	0 Participants	0 Participants
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) Week 8	0 Participants	0 Participants
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) Week 12	0 Participants	0 Participants
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) Week 18	1 Participants	0 Participants
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) Week 24	0 Participants	0 Participants
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) Week 28	2 Participants	1 Participants
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) Week 40	2 Participants	0 Participants
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) Week 52	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=8 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=5 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) HOMA-B	-2.58 percentage (%HOMA-B and %HOMA-S) Standard Deviation 130.435	42.02 percentage (%HOMA-B and %HOMA-S) Standard Deviation 183.869
Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) HOMA-S	9.85 percentage (%HOMA-B and %HOMA-S) Standard Deviation 12.366	2.36 percentage (%HOMA-B and %HOMA-S) Standard Deviation 7.631

SECONDARY outcome

Timeframe: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52

Population: 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.

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).

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=50 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=22 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 4	10.0 percentage of participants	9.1 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 8	4.0 percentage of participants	4.5 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 12	2.0 percentage of participants	0 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 18	0 percentage of participants	0 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 24	0 percentage of participants	0 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 28	4.0 percentage of participants	0 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 40	0 percentage of participants	0 percentage of participants
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 52	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52

Population: 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.

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.

Outcome measures

Measure	Controlled Assessment Period - Exenatide n=55 Participants Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=19 Participants Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Baseline	NA picograms per milliliter Geometric Coefficient of Variation NA Not calculated as below the lower limit of quantification.	—
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 4	41.51 picograms per milliliter Geometric Coefficient of Variation 91.9	—
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 8	130.60 picograms per milliliter Geometric Coefficient of Variation 83.8	—
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 12	163.58 picograms per milliliter Geometric Coefficient of Variation 92.3	—
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 24	140.81 picograms per milliliter Geometric Coefficient of Variation 84.0	NA picograms per milliliter Geometric Coefficient of Variation NA Not calculated as below the lower limit of quantification.
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) Week 52	88.88 picograms per milliliter Geometric Coefficient of Variation 79.2	105.56 picograms per milliliter Geometric Coefficient of Variation 154.9

Adverse Events

Controlled Assessment Period - Exenatide

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Controlled Assessment Period - Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Extension Period - Exenatide

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Extension Period - Placebo to Exenatide

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Controlled Assessment Period - Exenatide n=59 participants at risk Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=23 participants at risk Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.	Extension Period - Exenatide n=50 participants at risk 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.	Extension Period - Placebo to Exenatide n=22 participants at risk 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.
Gastrointestinal disorders Gastritis	0.00% 0/59 • 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. 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).	0.00% 0/23 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	0.00% 0/22 • 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. 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).
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/59 • 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. 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).	4.3% 1/23 • Number of events 1 • 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. 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).	0.00% 0/50 • 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. 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).	0.00% 0/22 • 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. 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).
Infections and infestations Abscess limb	1.7% 1/59 • Number of events 1 • 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. 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).	0.00% 0/23 • 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. 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).	0.00% 0/50 • 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. 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).	0.00% 0/22 • 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. 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).
Infections and infestations Cellulitis	0.00% 0/59 • 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. 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).	0.00% 0/23 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	0.00% 0/22 • 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. 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).
Infections and infestations Pneumonia	0.00% 0/59 • 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. 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).	0.00% 0/23 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	0.00% 0/22 • 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. 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).
Psychiatric disorders Major depression	1.7% 1/59 • Number of events 1 • 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. 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).	0.00% 0/23 • 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. 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).	0.00% 0/50 • 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. 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).	0.00% 0/22 • 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. 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).
Psychiatric disorders Suicidal ideation	0.00% 0/59 • 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. 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).	0.00% 0/23 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	4.5% 1/22 • Number of events 1 • 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. 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).

Other adverse events

Measure	Controlled Assessment Period - Exenatide n=59 participants at risk Patients received exenatide 2 mg SC injection once weekly for 24 weeks during the controlled assessment period.	Controlled Assessment Period - Placebo n=23 participants at risk Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks during the controlled assessment period.	Extension Period - Exenatide n=50 participants at risk 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.	Extension Period - Placebo to Exenatide n=22 participants at risk 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.
Gastrointestinal disorders Abdominal pain	3.4% 2/59 • Number of events 5 • 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. 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).	13.0% 3/23 • Number of events 3 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	0.00% 0/22 • 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. 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).
Gastrointestinal disorders Abdominal pain upper	5.1% 3/59 • Number of events 3 • 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. 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).	0.00% 0/23 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	0.00% 0/22 • 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. 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).
Gastrointestinal disorders Diarrhoea	8.5% 5/59 • Number of events 5 • 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. 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).	4.3% 1/23 • Number of events 1 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	0.00% 0/22 • 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. 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).
Gastrointestinal disorders Nausea	6.8% 4/59 • Number of events 4 • 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. 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).	4.3% 1/23 • Number of events 1 • 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. 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).	0.00% 0/50 • 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. 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).	4.5% 1/22 • Number of events 1 • 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. 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).
Gastrointestinal disorders Vomiting	5.1% 3/59 • Number of events 3 • 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. 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).	0.00% 0/23 • 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. 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).	4.0% 2/50 • Number of events 2 • 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. 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).	0.00% 0/22 • 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. 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).
General disorders Injection site erythema	5.1% 3/59 • Number of events 3 • 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. 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).	4.3% 1/23 • Number of events 1 • 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. 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).	0.00% 0/50 • 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. 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).	0.00% 0/22 • 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. 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).
Infections and infestations Nasopharyngitis	6.8% 4/59 • Number of events 5 • 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. 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).	8.7% 2/23 • Number of events 3 • 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. 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).	2.0% 1/50 • Number of events 1 • 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. 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).	4.5% 1/22 • Number of events 2 • 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. 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).
Infections and infestations Upper respiratory tract infection	10.2% 6/59 • Number of events 6 • 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. 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).	0.00% 0/23 • 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. 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).	4.0% 2/50 • Number of events 2 • 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. 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).	0.00% 0/22 • 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. 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).
Infections and infestations Urinary tract infection	5.1% 3/59 • Number of events 4 • 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. 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).	8.7% 2/23 • Number of events 2 • 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. 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).	0.00% 0/50 • 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. 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).	0.00% 0/22 • 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. 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).
Metabolism and nutrition disorders Hyperglycaemia	1.7% 1/59 • Number of events 2 • 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. 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).	4.3% 1/23 • Number of events 1 • 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. 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).	0.00% 0/50 • 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. 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).	9.1% 2/22 • Number of events 2 • 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. 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).
Metabolism and nutrition disorders Hypoglycaemia	5.1% 3/59 • Number of events 4 • 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. 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).	0.00% 0/23 • 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. 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).	2.0% 1/50 • Number of events 2 • 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. 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).	0.00% 0/22 • 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. 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).
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 3/59 • Number of events 3 • 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. 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).	0.00% 0/23 • 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. 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).	0.00% 0/50 • 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. 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).	0.00% 0/22 • 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. 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).
Nervous system disorders Headache	6.8% 4/59 • Number of events 5 • 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. 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).	8.7% 2/23 • Number of events 3 • 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. 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).	4.0% 2/50 • Number of events 2 • 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. 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).	4.5% 1/22 • Number of events 1 • 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. 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).
Respiratory, thoracic and mediastinal disorders Cough	6.8% 4/59 • Number of events 5 • 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. 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).	4.3% 1/23 • Number of events 1 • 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. 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).	0.00% 0/50 • 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. 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).	9.1% 2/22 • Number of events 3 • 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. 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).

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place