Trial Outcomes & Findings for Comparison of Lixisenatide Injected Prior to the Main Meal of the Day Versus Prior to Breakfast in Type 2 Diabetic Patients on Metformin (NCT NCT01517412)

Last Updated: 2016-10-14

Results Overview

Change in HbA1C was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using last observation carried forward (LOCF). On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

451 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2016-10-14

Participant Flow

The study was conducted at 82 centers in 10 countries. A total of 734 participants were screened between February 15, 2012 and October 16, 2012. 283 participants were screen failures; main reason for screen failure was that glycosylated hemoglobin (HbA1c) values were out of protocol defined range. 451 participants were randomized.

Participants were stratified according to main meal of day (breakfast, lunch or dinner) and screening values of HbA1c (\<8% or ≥8%).

Participant milestones

Participant milestones
Measure	Lixisenatide Main Meal Lixisenatide 10 mcg subcutaneous (SC) injection once daily (QD) within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Overall Study STARTED	225	226
Overall Study COMPLETED	189	202
Overall Study NOT COMPLETED	36	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Lixisenatide Main Meal Lixisenatide 10 mcg subcutaneous (SC) injection once daily (QD) within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Overall Study Adverse Event	10	11
Overall Study Lack of Efficacy	10	5
Overall Study Poor compliance to protocol	8	3
Overall Study Other than specified above	8	5

Baseline Characteristics

Comparison of Lixisenatide Injected Prior to the Main Meal of the Day Versus Prior to Breakfast in Type 2 Diabetic Patients on Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lixisenatide Main Meal n=225 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=226 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Total n=451 Participants Total of all reporting groups
Age, Continuous	56.3 years STANDARD_DEVIATION 10.6 • n=5 Participants	57.5 years STANDARD_DEVIATION 9.7 • n=7 Participants	56.9 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	124 Participants n=5 Participants	129 Participants n=7 Participants	253 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	97 Participants n=7 Participants	198 Participants n=5 Participants
Race Caucasian/White	211 participants n=5 Participants	211 participants n=7 Participants	422 participants n=5 Participants
Race Black	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Race Asian/Oriental	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants
Ethnicity Hispanic	11 participants n=5 Participants	12 participants n=7 Participants	23 participants n=5 Participants
Ethnicity Non-Hispanic	214 participants n=5 Participants	214 participants n=7 Participants	428 participants n=5 Participants
Number of Participants with Categorical Body Mass Index (BMI) <30 kg/m^2	51 participants n=5 Participants	60 participants n=7 Participants	111 participants n=5 Participants
Number of Participants with Categorical Body Mass Index (BMI) ≥30 kg/m^2	174 participants n=5 Participants	166 participants n=7 Participants	340 participants n=5 Participants
BMI, Continuous	33.47 kg/m^2 STANDARD_DEVIATION 4.50 • n=5 Participants	32.77 kg/m^2 STANDARD_DEVIATION 4.62 • n=7 Participants	33.12 kg/m^2 STANDARD_DEVIATION 4.57 • n=5 Participants
HbA1c	7.85 Percentage of hemoglobin STANDARD_DEVIATION 0.76 • n=5 Participants	7.93 Percentage of hemoglobin STANDARD_DEVIATION 0.78 • n=7 Participants	7.89 Percentage of hemoglobin STANDARD_DEVIATION 0.77 • n=5 Participants
Fasting Plasma Glucose (FPG)	9.22 mmol/L STANDARD_DEVIATION 2.03 • n=5 Participants	9.31 mmol/L STANDARD_DEVIATION 2.04 • n=7 Participants	9.26 mmol/L STANDARD_DEVIATION 2.03 • n=5 Participants
Average 7-point Self-monitored Plasma Glucose (SMPG)	9.41 mmol/L STANDARD_DEVIATION 2.01 • n=5 Participants	9.71 mmol/L STANDARD_DEVIATION 2.13 • n=7 Participants	9.56 mmol/L STANDARD_DEVIATION 2.07 • n=5 Participants
Duration of Diabetes	6.69 years STANDARD_DEVIATION 4.92 • n=5 Participants	7.78 years STANDARD_DEVIATION 5.56 • n=7 Participants	7.24 years STANDARD_DEVIATION 5.27 • n=5 Participants
Metformin Daily Dose	2040.7 mg STANDARD_DEVIATION 390.0 • n=5 Participants	2091.2 mg STANDARD_DEVIATION 1255.3 • n=7 Participants	2066.0 mg STANDARD_DEVIATION 929.6 • n=5 Participants
Randomization Strata of Main Meal of the Day Breakfast	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Randomization Strata of Main Meal of the Day Lunch	116 participants n=5 Participants	117 participants n=7 Participants	233 participants n=5 Participants
Randomization Strata of Main Meal of the Day Dinner	89 participants n=5 Participants	89 participants n=7 Participants	178 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Modified intent-to-treat (mITT) population: all randomized participants who received at least one dose of study drug and had both baseline and at least one post-baseline assessment of any primary or secondary efficacy endpoints, irrespective of compliance with study protocol and procedures.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=218 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=222 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Change in HbA1c From Baseline to Week 24	-0.65 Percentage of hemoglobin Standard Error 0.074	-0.74 Percentage of hemoglobin Standard Error 0.074

SECONDARY outcome

Timeframe: Week 24

Population: mITT population.

Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=218 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=222 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Percentage of Participants With HbA1c Level <7 % or ≤6.5% at Week 24 HbA1c <7%	43.6 Percentage of participants	42.8 Percentage of participants
Percentage of Participants With HbA1c Level <7 % or ≤6.5% at Week 24 HbA1c ≤6.5%	22.5 Percentage of participants	25.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population.

Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime two times in a week before baseline, before visit Week 8, before visit Week 12 and before visit week 24. The average value across the profiles performed in the week a visit for the 7-time points was calculated. Change in average 7-point SMPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to the day of last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline 7-point SMPG assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=202 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=200 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Change in Average 7-point SMPG Profiles From Baseline to Week 24	-0.80 mmol/L Standard Error 0.145	-1.10 mmol/L Standard Error 0.145

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population.

Change in FPG was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 1 day after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline FPG assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=220 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=222 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Change in FPG From Baseline to Week 24	-0.35 mmol/L Standard Error 0.192	-0.57 mmol/L Standard Error 0.193

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population.

Change in body weight was calculated by subtracting baseline value from Week 24 value. Missing data was imputed using LOCF. On-treatment period for this efficacy variable was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=220 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=224 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Change in Body Weight From Baseline to Week 24	-2.60 kg Standard Error 0.320	-2.80 kg Standard Error 0.319

SECONDARY outcome

Timeframe: Week 24

Population: mITT population.

Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemic episode with an accompanying PG\<60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate if no PG measurement was available. On-treatment period for symptomatic hypoglycemia assessment was defined as time from first dose of study drug up to 1 day after last dose of study drug. Participants without any post-baseline on-treatment value for HbA1c were counted as non-responders if they experienced at least one symptomatic hypoglycemia. Otherwise, they were counted as missing.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=218 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=222 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Percentage of Participants Who Reached the Target of HbA1c <7% at Week 24 And Did Not Experience Confirmed Symptomatic Hypoglycemia (Plasma Glucose [PG] <60 mg/dL [3.3 mmol/L]) During 24-Week Treatment Period	40.4 Percentage of participants	41.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: mITT population.

Participants without post-baseline on-treatment values for (HbA1c and body weight) that were no more than 30 days apart were counted as non-responders if at least one of the components (HbA1c and/or body weight) was available and showed no response. Otherwise, they were counted as missing.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=218 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=223 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Percentage of Participants Who Reached the Target of HbA1c <7% And Had No Body Weight Gain at Week 24	40.8 Percentage of participants	38.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: mITT population.

Participants without post-baseline on-treatment values (for HbA1c and body weight) that were no more than 30 days apart not more than 30-days apart were counted as non-responders if at least one of components (HbA1c and/or body weight) was available and showed no response. Otherwise, they were counted as missing.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=218 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=223 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Percentage of Participants Who Reached the Target of HbA1c <7% And Had No Body Weight Gain at Week 24 And Did Not Experience Confirmed Symptomatic Hypoglycemia (PG<60 mg/dL [3.3 mmol/L]) During the 24-Week Treatment Period	38.1 Percentage of participants	37.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: mITT population.

On-treatment period for 2-hour PPG assessment was defined as the time from the first dose of study drug up to the day of last dose of study drug. Participants without post-baseline on-treatment values (for HbA1c and 2-hour PPG) that were no more than 30-days apart were counted as non-responders if at least one of the components (HbA1cand/or 2-hour PPG) was available and showed no response. Otherwise, they were counted as missing.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=218 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=221 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Percentage of Participants Who Reached the Target of HbA1c <7% And Had a 2-hour Postprandial Plasma Glucose (PPG) <140mg/dL After Breakfast or Main Meal At Week 24	28.9 Percentage of participants	27.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: mITT population.

DTSQ is a validated measure to assess how satisfied participants with diabetes are with their treatment and how they perceive hyper- and hypoglycemia. It consists of 8 questions which are answered on a Likert scale from 0 to 6. DTSQ treatment satisfaction score is the sum of question 1, 4, 5, 6, 7 and 8 scores and ranges between 0 and 36, where higher scores indicate more treatment satisfaction. On-treatment period for treatment satisfaction assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. Missing data was imputed using LOCF. Here, number of participants analyzed = participants with both baseline and Week 24 DTSQ score assessment during on-treatment period.

Outcome measures

Outcome measures
Measure	Lixisenatide Main Meal n=204 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=215 Participants Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Change in Diabetes Treatment Satisfaction Questionnaire Score (DTSQs) From Baseline to Week 24	3.01 Units on a scale Standard Error 0.546	3.54 Units on a scale Standard Error 0.529

Adverse Events

Lixisenatide Main Meal

Serious events: 7 serious events

Other events: 65 other events

Deaths: 0 deaths

Lixisenatide Breakfast

Serious events: 7 serious events

Other events: 60 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lixisenatide Main Meal n=225 participants at risk Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=226 participants at risk Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Infections and infestations Cellulitis	0.44% 1/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.00% 0/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Infections and infestations Postoperative wound infection	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell renal cell carcinoma	0.44% 1/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.00% 0/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Nervous system disorders Cerebral infarction	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	0.44% 1/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.00% 0/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Vascular disorders Peripheral arterial occlusive disease	0.44% 1/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.00% 0/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal hernia	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal strangulated hernia	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Renal and urinary disorders Renal colic	0.89% 2/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.00% 0/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Renal and urinary disorders Cystitis noninfective	0.44% 1/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.00% 0/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Renal and urinary disorders Calculus ureteric	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	0.44% 1/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Lixisenatide Main Meal n=225 participants at risk Lixisenatide 10 mcg SC injection QD within 1 hour before "main meal of the day" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.	Lixisenatide Breakfast n=226 participants at risk Lixisenatide 10 mcg SC injection QD within 1 hour before "breakfast" for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 24 on top of metformin.
Infections and infestations Nasopharyngitis	9.8% 22/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	7.1% 16/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	6.7% 15/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	3.1% 7/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	3.6% 8/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	7.1% 16/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	14.7% 33/225 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.	15.5% 35/226 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 171) regardless of seriousness or relationship to investigational medicinal product (IMP). Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (time from the first dose of study drug up to 3 days after the last dose of study drug). Safety population defined as all randomized participants who received at least one dose of study drug.

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