Trial Outcomes & Findings for GLP-1 Receptor Agonist Lixisenatide (Morning or Evening) in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin (NCT NCT00712673)

Last Updated: 2016-12-15

Results Overview

Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in Modified Intent-to-treat (mITT) population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

680 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2016-12-15

Participant Flow

The study was conducted at 133 centers in 16 countries between June 30, 2008 and March 09, 2011. The overall duration of treatment was at least 76 weeks (24 weeks main double-blind treatment; variable double-blind extension treatment).

A total of 1374 patients were screened of which 694 (50.5%) were screen failures; main reason for screen failure was glycosylated hemoglobin (HbA1c) values being out of the defined protocol range (greater than or equal to 7% and less than or equal to 10%). A total of 680 patients were randomized.

Participant milestones

Participant milestones
Measure	Placebo (Morning Injection) 2-step initiation morning regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Placebo (Evening Injection) 2-step initiation evening regimen of volume matching placebo: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
Overall Study STARTED	85	85	255	255
Overall Study Safety Population	85	85	255	255
Overall Study Modified Intent-to-Treat(mITT)Population	85	85	255	255
Overall Study Subgroup for Standardized Meal Test	85	0	255	0
Overall Study COMPLETED	64	64	198	185
Overall Study NOT COMPLETED	21	21	57	70

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Morning Injection) 2-step initiation morning regimen of volume matching placebo: 10 microgram (mcg) once daily (QD) subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Placebo (Evening Injection) 2-step initiation evening regimen of volume matching placebo: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.
Overall Study Adverse Event	3	3	21	26
Overall Study Lack of Efficacy	2	8	8	6
Overall Study Poor Compliance to Protocol	3	3	4	16
Overall Study Lost to Follow-up	1	0	2	0
Overall Study Withdrawal by Subject	6	7	15	20
Overall Study Familial and Personal Reasons	5	0	5	2
Overall Study Investigator's Decision	1	0	0	0
Overall Study Protocol Violation	0	0	2	0

Baseline Characteristics

GLP-1 Receptor Agonist Lixisenatide (Morning or Evening) in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Combined) n=170 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=255 Participants 2-step initiation morning regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Lixisenatide (Evening Injection) n=255 Participants 2-step initiation evening regimen of lixisenatide: 10 mcg QD subcutaneously for 1 week, followed by 15 mcg QD for 1 week, then 20 mcg QD up to end of treatment.	Total n=680 Participants Total of all reporting groups
Body Weight	90.15 kilogram (kg) STANDARD_DEVIATION 20.14 • n=93 Participants	90.09 kilogram (kg) STANDARD_DEVIATION 21.10 • n=4 Participants	89.05 kilogram (kg) STANDARD_DEVIATION 20.74 • n=27 Participants	89.71 kilogram (kg) STANDARD_DEVIATION 20.70 • n=483 Participants
Age, Continuous	55.0 years STANDARD_DEVIATION 9.4 • n=93 Participants	54.5 years STANDARD_DEVIATION 9.2 • n=4 Participants	54.8 years STANDARD_DEVIATION 10.4 • n=27 Participants	54.7 years STANDARD_DEVIATION 9.7 • n=483 Participants
Gender Female	89 Participants n=93 Participants	157 Participants n=4 Participants	141 Participants n=27 Participants	387 Participants n=483 Participants
Gender Male	81 Participants n=93 Participants	98 Participants n=4 Participants	114 Participants n=27 Participants	293 Participants n=483 Participants
Race/Ethnicity, Customized Race: Caucasian/White	155 participants n=93 Participants	221 participants n=4 Participants	228 participants n=27 Participants	604 participants n=483 Participants
Race/Ethnicity, Customized Race: Black	4 participants n=93 Participants	7 participants n=4 Participants	6 participants n=27 Participants	17 participants n=483 Participants
Race/Ethnicity, Customized Race: Asian/Oriental	11 participants n=93 Participants	22 participants n=4 Participants	20 participants n=27 Participants	53 participants n=483 Participants
Race/Ethnicity, Customized Race: Other	0 participants n=93 Participants	5 participants n=4 Participants	1 participants n=27 Participants	6 participants n=483 Participants
Race/Ethnicity, Customized Ethnicity: Hispanic	49 participants n=93 Participants	96 participants n=4 Participants	98 participants n=27 Participants	243 participants n=483 Participants
Race/Ethnicity, Customized Ethnicity: Non Hispanic	121 participants n=93 Participants	159 participants n=4 Participants	157 participants n=27 Participants	437 participants n=483 Participants
Glycosylated Hemoglobin (HbA1c)	8.06 percentage of hemoglobin STANDARD_DEVIATION 0.90 • n=93 Participants	8.04 percentage of hemoglobin STANDARD_DEVIATION 0.86 • n=4 Participants	8.09 percentage of hemoglobin STANDARD_DEVIATION 0.91 • n=27 Participants	8.06 percentage of hemoglobin STANDARD_DEVIATION 0.89 • n=483 Participants
Fasting Plasma Glucose (FPG)	9.51 millimole per liter (mmol/L) STANDARD_DEVIATION 2.28 • n=93 Participants	9.43 millimole per liter (mmol/L) STANDARD_DEVIATION 2.15 • n=4 Participants	9.31 millimole per liter (mmol/L) STANDARD_DEVIATION 2.25 • n=27 Participants	9.40 millimole per liter (mmol/L) STANDARD_DEVIATION 2.22 • n=483 Participants
2-hour Postprandial Plasma Glucose (PPG)	15.51 mmol/L STANDARD_DEVIATION 3.43 • n=93 Participants	15.62 mmol/L STANDARD_DEVIATION 3.97 • n=4 Participants	15.46 mmol/L STANDARD_DEVIATION 4.03 • n=27 Participants	15.53 mmol/L STANDARD_DEVIATION 3.86 • n=483 Participants
Homeostasis Model Assessment for Beta-cell Function (HOMA-beta)	41.48 percentage of normal beta cells function STANDARD_DEVIATION 42.12 • n=93 Participants	42.82 percentage of normal beta cells function STANDARD_DEVIATION 32.33 • n=4 Participants	45.21 percentage of normal beta cells function STANDARD_DEVIATION 46.09 • n=27 Participants	43.38 percentage of normal beta cells function STANDARD_DEVIATION 40.38 • n=483 Participants
Adiponectin	5.61 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 3.26 • n=93 Participants	5.25 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 2.90 • n=4 Participants	5.25 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 2.93 • n=27 Participants	5.34 microgram per milliliter (mcg/mL) STANDARD_DEVIATION 3.01 • n=483 Participants
Fasting Plasma Insulin (FPI)	75.79 picomole per liter (pmol/L) STANDARD_DEVIATION 48.02 • n=93 Participants	83.68 picomole per liter (pmol/L) STANDARD_DEVIATION 63.60 • n=4 Participants	77.90 picomole per liter (pmol/L) STANDARD_DEVIATION 65.46 • n=27 Participants	79.53 picomole per liter (pmol/L) STANDARD_DEVIATION 60.84 • n=483 Participants
2-hour Postprandial Plasma Insulin (PPI)	374.28 pmol/L STANDARD_DEVIATION 266.55 • n=93 Participants	380.53 pmol/L STANDARD_DEVIATION 260.96 • n=4 Participants	378.67 pmol/L STANDARD_DEVIATION 328.19 • n=27 Participants	378.30 pmol/L STANDARD_DEVIATION 289.51 • n=483 Participants
Fasting C-peptide	0.90 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.36 • n=93 Participants	0.97 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.43 • n=4 Participants	0.94 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.43 • n=27 Participants	0.94 nanomole per liter (nmol/L) STANDARD_DEVIATION 0.41 • n=483 Participants
2-hour Postprandial C-peptide	2.46 nmol/L STANDARD_DEVIATION 1.08 • n=93 Participants	2.56 nmol/L STANDARD_DEVIATION 1.11 • n=4 Participants	2.42 nmol/L STANDARD_DEVIATION 1.16 • n=27 Participants	2.48 nmol/L STANDARD_DEVIATION 1.12 • n=483 Participants
Fasting Glucagon	87.92 nanogram per liter (ng/L) STANDARD_DEVIATION 29.05 • n=93 Participants	88.89 nanogram per liter (ng/L) STANDARD_DEVIATION 32.90 • n=4 Participants	88.53 nanogram per liter (ng/L) STANDARD_DEVIATION 27.30 • n=27 Participants	88.51 nanogram per liter (ng/L) STANDARD_DEVIATION 29.88 • n=483 Participants
2-hour Postprandial Glucagon	101.30 ng/L STANDARD_DEVIATION 33.88 • n=93 Participants	101.46 ng/L STANDARD_DEVIATION 34.54 • n=4 Participants	100.90 ng/L STANDARD_DEVIATION 34.12 • n=27 Participants	101.21 ng/L STANDARD_DEVIATION 34.17 • n=483 Participants
Fasting Proinsulin	31.68 pmol/L STANDARD_DEVIATION 20.10 • n=93 Participants	34.93 pmol/L STANDARD_DEVIATION 24.14 • n=4 Participants	32.35 pmol/L STANDARD_DEVIATION 18.45 • n=27 Participants	33.16 pmol/L STANDARD_DEVIATION 21.16 • n=483 Participants
2-hour Postprandial Proinsulin	83.48 pmol/L STANDARD_DEVIATION 58.02 • n=93 Participants	83.71 pmol/L STANDARD_DEVIATION 54.65 • n=4 Participants	77.19 pmol/L STANDARD_DEVIATION 53.44 • n=27 Participants	81.15 pmol/L STANDARD_DEVIATION 55.05 • n=483 Participants
Glucose Excursion	5.64 mmol/L STANDARD_DEVIATION 2.81 • n=93 Participants	6.09 mmol/L STANDARD_DEVIATION 3.09 • n=4 Participants	5.80 mmol/L STANDARD_DEVIATION 3.13 • n=27 Participants	5.87 mmol/L STANDARD_DEVIATION 3.04 • n=483 Participants
Body Mass Index (BMI)	33.12 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.45 • n=93 Participants	33.22 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.85 • n=4 Participants	32.47 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.77 • n=27 Participants	32.91 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.36 • n=483 Participants
Duration of Diabetes	5.87 years STANDARD_DEVIATION 4.72 • n=93 Participants	6.18 years STANDARD_DEVIATION 5.25 • n=4 Participants	6.21 years STANDARD_DEVIATION 5.40 • n=27 Participants	6.11 years STANDARD_DEVIATION 5.17 • n=483 Participants
Duration of Metformin Treatment	3.34 years STANDARD_DEVIATION 3.45 • n=93 Participants	3.73 years STANDARD_DEVIATION 3.34 • n=4 Participants	3.68 years STANDARD_DEVIATION 3.90 • n=27 Participants	3.61 years STANDARD_DEVIATION 3.59 • n=483 Participants
Metformin Daily Dose	2001.18 milligram (mg) STANDARD_DEVIATION 439.70 • n=93 Participants	1968.82 milligram (mg) STANDARD_DEVIATION 446.99 • n=4 Participants	1942.65 milligram (mg) STANDARD_DEVIATION 406.17 • n=27 Participants	1967.10 milligram (mg) STANDARD_DEVIATION 430.22 • n=483 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: mITT population:all randomized patients who received at least 1 dose;had baseline,at least 1 post-baseline efficacy assessment, irrespective of compliance with study protocol/procedures. Last observation carried forward used. Number of patients analyzed=patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=164 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=244 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=239 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24	-0.38 percentage of hemoglobin Standard Error 0.075	-0.87 percentage of hemoglobin Standard Error 0.065	-0.75 percentage of hemoglobin Standard Error 0.066	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using last observation carried forward (LOCF). Here, number of patients analyzed = patients with baseline and at least 1 post-baseline FPG assessment during on-treatment period.

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=170 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=253 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=255 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	-0.25 mmol/L Standard Error 0.166	-1.19 mmol/L Standard Error 0.145	-0.81 mmol/L Standard Error 0.146	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Subgroup for standardized meal test (patients from morning injection arms only) as pre-specified in the protocol. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline 2-hour PPG assessment during on-treatment period.

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=64 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=200 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24	-1.41 mmol/L Standard Error 0.588	-5.92 mmol/L Standard Error 0.415	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=168 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=248 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=249 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Body Weight at Week 24	-1.64 kilogram Standard Error 0.269	-2.01 kilogram Standard Error 0.234	-2.02 kilogram Standard Error 0.236	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline plasma insulin assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=157 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=237 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=229 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Fasting Plasma Insulin (FPI) at Week 24	-6.23 pmol/L Standard Error 3.254	-5.09 pmol/L Standard Error 2.812	-1.88 pmol/L Standard Error 2.862	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to the last dosing day of the study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=54 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=181 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in 2-Hour Postprandial Plasma Insulin (PPI) at Week 24	-25.67 pmol/L Standard Error 38.028	-87.24 pmol/L Standard Error 24.885	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=48 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=154 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Fasting Proinsulin at Week 24	-3.78 pmol/L Standard Error 2.246	-7.78 pmol/L Standard Error 1.414	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=43 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=129 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in 2-Hour Postprandial Proinsulin at Week 24	-6.83 pmol/L Standard Error 5.253	-18.88 pmol/L Standard Error 3.406	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=63 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=192 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Fasting C-Peptide at Week 24	-0.13 nmol/L Standard Error 0.031	-0.10 nmol/L Standard Error 0.020	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=62 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=193 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in 2-Hour Postprandial C-Peptide at Week 24	-0.20 nmol/L Standard Error 0.137	-0.46 nmol/L Standard Error 0.097	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=59 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=191 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Fasting Glucagon at Week 24	-13.53 ng/L Standard Error 3.054	-13.27 ng/L Standard Error 2.074	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=62 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=191 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in 2-Hour Postprandial Glucagon at Week 24	-12.79 ng/L Standard Error 3.551	-27.04 ng/L Standard Error 2.467	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline adiponectin assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=155 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=236 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=227 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Adiponectin at Week 24	0.54 mcg/mL Standard Error 0.183	0.55 mcg/mL Standard Error 0.159	0.58 mcg/mL Standard Error 0.160	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HOMA-beta assessment during on-treatment period.

Beta cell function was assessed by HOMA-beta. HOMA-beta (% of normal beta cells function) = (20 multiplied by fasting plasma insulin \[micro unit per milliliter\]) divided by (FPG \[mmol/L\] minus 3.5). Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 1 day after last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=157 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=235 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=226 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Beta-cell Function Assessed by Homeostasis Model Assessment for Beta-cell Function (HOMA-beta) at Week 24	-4.16 % of normal beta cells function Standard Error 2.823	7.96 % of normal beta cells function Standard Error 2.450	4.80 % of normal beta cells function Standard Error 2.486	—	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: mITT population.

Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG \>270 milligram/deciliter (mg/dL) (15.0 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG \>240 mg/dL (13.3 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG \>200 mg/dL (11.1 mmol/L) or HbA1c \>8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=170 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=255 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=255 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Percentage of Patients Requiring Rescue Therapy During the Main 24-Week Period	10.6 percentage of participants	2.7 percentage of participants	3.9 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.

The on-treatment period for this efficacy variable is time from the first dose of study drug and up to 3 days after the last dose of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy. For a patient to be included in mITT population, both baseline and at least 1 post baseline assessment for at least 1 efficacy variable, were required.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=164 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=244 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=239 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24	22.0 percentage of participants	43.0 percentage of participants	40.6 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline HbA1c assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=164 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=244 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=239 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24	10.4 percentage of participants	23.8 percentage of participants	19.2 percentage of participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 24

Population: Subgroup for standardized meal teat. Missing data was imputed using LOCF. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline glucose excursion assessment during on-treatment period.

Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is time from the first dose of study drug and up to last dosing day of study drug, on or before Visit 12 (Week 24) or Day 169 if Visit 12 is not available, and before the introduction of rescue therapy.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=63 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=198 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Change From Baseline in Glucose Excursion at Week 24	-0.76 mmol/L Standard Error 0.483	-4.64 mmol/L Standard Error 0.340	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 24

Population: mITT population. Here, number of patients analyzed = patients with baseline and at least 1 post-baseline body weight assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=168 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=248 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=249 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24	11.3 percentage of participants	14.9 percentage of participants	19.3 percentage of participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose of study drug up to 3 days after the last dose administration

Population: Safety population included all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.

Outcome measures

Outcome measures
Measure	Placebo (Combined) n=85 Participants Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=85 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=170 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Morning Injection) n=255 Participants 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=255 Participants 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) n=510 Participants Included all patients who received 2-step initiation, morning and evening regimen of lixisenatide.
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia Symptomatic Hypoglycemia	0 participants	4 participants	4 participants	18 participants	22 participants	40 participants
Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia Severe Symptomatic Hypoglycemia	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

Adverse Events

Placebo (Morning Injection)

Serious events: 2 serious events

Other events: 45 other events

Deaths: 0 deaths

Placebo (Evening Injection)

Serious events: 9 serious events

Other events: 50 other events

Deaths: 0 deaths

Placebo (Combined)

Serious events: 11 serious events

Other events: 95 other events

Deaths: 0 deaths

Lixisenatide (Morning Injection)

Serious events: 21 serious events

Other events: 182 other events

Deaths: 0 deaths

Lixisenatide (Evening Injection)

Serious events: 26 serious events

Other events: 169 other events

Deaths: 0 deaths

Lixisenatide (Combined)

Serious events: 47 serious events

Other events: 351 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo (Morning Injection) n=85 participants at risk 2-step initiation morning regimen of volume matching placebo.	Placebo (Evening Injection) n=85 participants at risk 2-step initiation evening regimen of volume matching placebo.	Placebo (Combined) n=170 participants at risk Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=255 participants at risk 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=255 participants at risk 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) n=510 participants at risk Included all patients who received 2-step initiation morning and evening regimen of lixisenatide.
Infections and infestations Anal abscess	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Bacterial sepsis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Escherichia urinary tract infection	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Influenza	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Pneumonia	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.78% 2/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 3/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Staphylococcal sepsis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Signet-ring cell carcinoma	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Endocrine disorders Hypothyroidism	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Metabolism and nutrition disorders Obesity	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Psychiatric disorders Insomnia	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Psychiatric disorders Psychosomatic disease	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Psychiatric disorders Suicide attempt	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Carpal tunnel syndrome	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Cerebral infarction	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Dizziness	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Hypertensive encephalopathy	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Lacunar infarction	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Ruptured cerebral aneurysm	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Eye disorders Retinal haemorrhage	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Eye disorders Vitreous haemorrhage	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Acute myocardial infarction	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 2/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Angina unstable	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 2/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Atrial fibrillation	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Atrioventricular block first degree	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Cardiac failure congestive	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Cardiomyopathy	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Coronary artery disease	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Cardiac disorders Ventricular extrasystoles	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Vascular disorders Hypertensive crisis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.78% 2/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 3/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Abdominal adhesions	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Gastric haemorrhage	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Gastritis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Haemorrhoids	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Inguinal hernia	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Inguinal hernia, obstructive	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Rectal polyp	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Hepatobiliary disorders Cholecystitis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Hepatobiliary disorders Cholelithiasis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 3/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.78% 4/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Renal and urinary disorders Nephrolithiasis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
General disorders Necrobiosis	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Investigations Pancreatic enzymes increased	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Dislocation of vertebra	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Fall	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Joint injury	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Skull fracture	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Spinal cord injury	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Surgical and medical procedures Cardiac pacemaker insertion	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Surgical and medical procedures Coronary artery bypass	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.39% 1/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.20% 1/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Other adverse events

Other adverse events
Measure	Placebo (Morning Injection) n=85 participants at risk 2-step initiation morning regimen of volume matching placebo.	Placebo (Evening Injection) n=85 participants at risk 2-step initiation evening regimen of volume matching placebo.	Placebo (Combined) n=170 participants at risk Included all patients who received 2-step initiation morning and evening regimen of volume matching placebo.	Lixisenatide (Morning Injection) n=255 participants at risk 2-step initiation morning regimen of lixisenatide.	Lixisenatide (Evening Injection) n=255 participants at risk 2-step initiation evening regimen of lixisenatide.	Lixisenatide (Combined) n=510 participants at risk Included all patients who received 2-step initiation morning and evening regimen of lixisenatide.
Infections and infestations Bronchitis	9.4% 8/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.2% 14/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.6% 22/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 6/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.5% 28/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Gastroenteritis	4.7% 4/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.7% 4/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.7% 8/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.5% 14/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.7% 12/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.1% 26/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Influenza	5.9% 5/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	10.6% 9/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.2% 14/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.8% 30/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.0% 28/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.4% 58/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Nasopharyngitis	12.9% 11/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	17.6% 15/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	15.3% 26/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	14.9% 38/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.8% 20/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.4% 58/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Pharyngitis	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.5% 3/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.9% 5/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 6/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.3% 16/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.3% 22/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Upper respiratory tract infection	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.8% 10/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	9.4% 16/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.6% 22/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 15/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.3% 37/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Infections and infestations Urinary tract infection	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 5/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.1% 7/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 15/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.9% 10/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.9% 25/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 5/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.9% 5/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	9.0% 23/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.0% 28/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	10.0% 51/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Dizziness	5.9% 5/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.5% 11/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 18/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.5% 14/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.3% 32/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Nervous system disorders Headache	9.4% 8/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	23.5% 20/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	16.5% 28/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	19.2% 49/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	16.5% 42/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	17.8% 91/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Vascular disorders Hypertension	3.5% 3/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.3% 9/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.7% 17/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 15/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	6.3% 32/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Respiratory, thoracic and mediastinal disorders Cough	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 5/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.1% 7/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.9% 10/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.5% 9/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.7% 19/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Abdominal pain	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 4/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.5% 14/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 6/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.9% 20/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Abdominal pain upper	3.5% 3/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.3% 9/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.3% 11/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.9% 10/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.1% 21/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Diarrhoea	11.8% 10/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.8% 10/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	11.8% 20/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	15.3% 39/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	14.1% 36/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	14.7% 75/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Dyspepsia	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.00% 0/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	0.59% 1/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 15/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.1% 13/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.5% 28/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Nausea	8.2% 7/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	10.6% 9/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	9.4% 16/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	25.1% 64/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	24.7% 63/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	24.9% 127/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Gastrointestinal disorders Vomiting	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.5% 3/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.3% 9/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	13.7% 35/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	15.7% 40/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	14.7% 75/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Musculoskeletal and connective tissue disorders Arthralgia	3.5% 3/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.9% 5/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 18/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.5% 9/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.3% 27/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Musculoskeletal and connective tissue disorders Back pain	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 6/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 12/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.2% 21/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.2% 21/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	8.2% 42/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.8% 3/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.5% 14/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.5% 9/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.5% 23/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
Musculoskeletal and connective tissue disorders Pain in extremity	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.2% 1/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	1.8% 3/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	7.1% 18/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.7% 12/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.9% 30/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.
General disorders Fatigue	3.5% 3/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.4% 2/85 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	2.9% 5/170 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	5.5% 14/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	3.5% 9/255 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.	4.5% 23/510 • First dose of study drug up to 3 days after the last dose administration Median exposure to study treatment were 564, 561.5 and 567.5 days for the morning lixisenatide, evening lixisenatide combined placebo treatment arms, respectively.The analysis was performed on safety population, defined as all randomized patients who were exposed to at least 1 dose of study drug, regardless of the amount of treatment administered.

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER