Trial Outcomes & Findings for Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin (NCT NCT01596504)

Results Overview

Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 milligram per decilitre (mg/dL) with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\]) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

142 participants

Primary outcome timeframe

0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 56

Results posted on

2016-10-14

Participant Flow

The study was conducted at 8 centers in Germany between 22 May 2012 to 25 July 2013.

A total of 236 participants were screened and 142 participants were randomized and treated.

Participant milestones

Participant milestones
Measure	Lixisenatide 20 μg Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Overall Study STARTED	48	47	47
Overall Study COMPLETED	46	44	46
Overall Study NOT COMPLETED	2	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Lixisenatide 20 μg Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Overall Study Participant's Private Reason	0	1	0
Overall Study Adverse Event	1	2	1
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lixisenatide 20 μg n=48 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=47 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=47 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.	Total n=142 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 7.4 • n=99 Participants	61.4 years STANDARD_DEVIATION 7.9 • n=107 Participants	62.6 years STANDARD_DEVIATION 9.4 • n=206 Participants	61.9 years STANDARD_DEVIATION 8.3 • n=7 Participants
Sex: Female, Male Female	15 Participants n=99 Participants	8 Participants n=107 Participants	14 Participants n=206 Participants	37 Participants n=7 Participants
Sex: Female, Male Male	33 Participants n=99 Participants	39 Participants n=107 Participants	33 Participants n=206 Participants	105 Participants n=7 Participants
Race Caucasian/White	48 participants n=99 Participants	46 participants n=107 Participants	47 participants n=206 Participants	141 participants n=7 Participants
Race Other	0 participants n=99 Participants	1 participants n=107 Participants	0 participants n=206 Participants	1 participants n=7 Participants
Metformin Use at Screening Yes	43 participants n=99 Participants	41 participants n=107 Participants	41 participants n=206 Participants	125 participants n=7 Participants
Metformin Use at Screening No	5 participants n=99 Participants	6 participants n=107 Participants	6 participants n=206 Participants	17 participants n=7 Participants
Weight	90.56 kg STANDARD_DEVIATION 13.09 • n=99 Participants	91.62 kg STANDARD_DEVIATION 13.92 • n=107 Participants	92.92 kg STANDARD_DEVIATION 15.33 • n=206 Participants	91.69 kg STANDARD_DEVIATION 14.07 • n=7 Participants
Body Mass Index (BMI)	30.68 (kg/m²) STANDARD_DEVIATION 4.34 • n=99 Participants	30.52 (kg/m²) STANDARD_DEVIATION 4.01 • n=107 Participants	31.17 (kg/m²) STANDARD_DEVIATION 4.34 • n=206 Participants	30.79 (kg/m²) STANDARD_DEVIATION 4.22 • n=7 Participants
HbA1c at Screening (Day -7)	7.22 percentage of haemoglobin STANDARD_DEVIATION 0.48 • n=99 Participants	7.19 percentage of haemoglobin STANDARD_DEVIATION 0.53 • n=107 Participants	7.33 percentage of haemoglobin STANDARD_DEVIATION 0.5 • n=206 Participants	7.25 percentage of haemoglobin STANDARD_DEVIATION 0.50 • n=7 Participants

PRIMARY outcome

Timeframe: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5 hours post study drug administration on Day 56

Population: Pharmacodynamic (PD) population defined as all randomized participants, who received at least one dose of lixisenatide 20 μg, liraglutide 1.2 mg or liraglutide 1.8 mg, and had both a baseline assessment and at least one post-baseline assessment of any primary or secondary PD variables, irrespective of compliance with study protocol and procedures.

Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 milligram per decilitre (mg/dL) with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\]) to 4 hours after breakfast start (time: 4.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours).

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=45 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in Plasma Glucose Corrected Area Under The Plasma Concentration-Time Curve (AUC) From Time 0.5 Hours to 4.5 Hours	-13.33 h*mmol/L Standard Error 1.11	-7.32 h*mmol/L Standard Error 1.12	-8.72 h*mmol/L Standard Error 1.16

SECONDARY outcome

Timeframe: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

Population: PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.

Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as limit of detection (LOD). Calculation of the AUC was made on Day -3 (baseline) and on Day 56 using the linear trapezoidal rule from time of breakfast start (30 minutes after study drug administration \[time: 0.5 hours\]) to 5 hours after breakfast start (time: 5.5 hours) and corrected by subtracting pre-breakfast plasma glucose concentration (time: 0.5 hours).

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=45 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours	-13.82 h*mmol/L Standard Error 1.19	-9.09 h*mmol/L Standard Error 1.21	-10.33 h*mmol/L Standard Error 1.25

SECONDARY outcome

Timeframe: Day 56

Population: PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.

Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. The 2-hour PPG test measured blood glucose 2 hours after start of a standardised breakfast.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Number of Participants With 2-Hour Post-prandial Plasma Glucose (PPG) <7.77 (mmol/L) at Day 56	35 participants	13 participants	11 participants

SECONDARY outcome

Timeframe: 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

Population: PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.

Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. PPG excursion was determined on Day -3 (Baseline) and Day 56 as the maximum change in PPG from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=45 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in PPG Excursion	-3.26 mmol/L Standard Error 0.4	-1.79 mmol/L Standard Error 0.4	-2.5 mmol/L Standard Error 0.42

SECONDARY outcome

Timeframe: 0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on Day 56

Population: PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.

Plasma glucose was assessed using the Gluco-quant Glucose/hexokinase assay. The range of the method was 3 to 1000 mg/dL with 1 mg/dL as LOD. The value of FPG on Day -3 was the baseline.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=45 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=45 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in Fasting Plasma Glucose (FPG)	0.1 mmol/L Standard Error 0.22	0.12 mmol/L Standard Error 0.22	0.13 mmol/L Standard Error 0.23

SECONDARY outcome

Timeframe: Before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime on Day -3 (Baseline) and on Day 56

Population: PD population. Number of participants analyzed = participants with 7 point SMPG assessment at specified time-points.

Seven-point SMPG (before breakfast, 2 hours post breakfast, before lunch, 2 hours post lunch, before dinner, 2 hours post dinner, and at bedtime) was measured using Freestyle Precision glucometer and average of the 7 measurements was calculated.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in Average 7-Point Self-Monitored Plasma Glucose (SMPG)	-0.69 mmol/L Standard Deviation 1.19	-0.76 mmol/L Standard Deviation 1.23	-1.2 mmol/L Standard Deviation 1.09

SECONDARY outcome

Timeframe: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day-3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

Population: PD population. Number of participants analyzed = participants with C-peptide assessment at specified time-points.

C-peptide was assessed using the Electro Chemiluminescence Immuno Assay.The range of the method was 0.2 to 25 nanogram per millilitre (ng/mL) and the LOD was 0.07 ng/mL. Measurement was done on Day -3 (Baseline) and Day 56 as the maximum change in C-peptide from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=45 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in Corrected C-Peptide AUC From Time 0.5 Hours to 5.5 Hours	-1.16 h*nmol/L Standard Error 0.37	1.23 h*nmol/L Standard Error 0.37	0.88 h*nmol/L Standard Error 0.39

SECONDARY outcome

Timeframe: 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours on Day -3 (baseline); 0.5 (prior to standardized breakfast), 0.67, 0.84, 1, 1.5, 2, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

Population: PD population. Number of participants analyzed = participants with glucagon assessment at specified time-points.

Glucagon was assessed using the radioimmunoassay. The range of the method was 4.7 to 150 picomole per litre (pmol/L). Measurement was done on Day -3 (Baseline) and Day 56 as the maximum change in glucagon from time of breakfast start (time: 0.5 hours) until 5 hours later (time: 5.5 hours) subtracted from pre-meal plasma concentration.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=45 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours	-16.56 h*ng/L Standard Error 19.43	11.58 h*ng/L Standard Error 19.86	5.6 h*ng/L Standard Error 20.3

SECONDARY outcome

Timeframe: Pre-dose (Hour 0) on Day 1 (Baseline) and Day 56

Population: Number of participants analyzed = participants with HbA1c assessment at specified time-points.

HbA1C was assessed using the high performance liquid chromatography method.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in HbA1c	-0.58 percentage of HbA1c Standard Error 0.06	-0.66 percentage of HbA1c Standard Error 0.06	-0.74 percentage of HbA1c Standard Error 0.06

SECONDARY outcome

Timeframe: Day -7 (Baseline), Day 56

Population: PD population. Number of participants analyzed=participants with insulin glargine dose assessment at specified time-points.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in Average Daily Insulin Glargine Dose	-4.7 units Standard Deviation 4.8	-4.6 units Standard Deviation 6.8	-4.0 units Standard Deviation 6.5

SECONDARY outcome

Timeframe: 0 (prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55

Population: PD population. Number of participants analyzed=participants with gastric emptying assessment at specified time-points.

Gastric emptying was measured using 13C-octanoic acid breath test by isotope-selective non-dispersive infrared spectrometry.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 55 in Gastric Emptying Half Life (t1/2)	453.56 minutes (min) Standard Error 58.24	175.31 minutes (min) Standard Error 58.49	130.49 minutes (min) Standard Error 60.27

SECONDARY outcome

Timeframe: 0 (7:30 clock time, prior to standardized breakfast), 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 hours on Day -4 (baseline) and on Day 55

Population: PD population. Number of participants analyzed = participants with gastric emptying at specified time-points.

Gastric emptying was measured using 13C-octanoic acid breath test by isotope-selective non-dispersive infrared spectrometry. Gastric emptying coefficient was derived from a mathematical formula that describes the gastric emptying rate and gives an overall index of gastric emptying.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 55 in Gastric Emptying Coefficient	-0.33 coefficient (unit-less) Standard Deviation 1.09	-0.34 coefficient (unit-less) Standard Deviation 0.53	-0.28 coefficient (unit-less) Standard Deviation 0.52

SECONDARY outcome

Timeframe: Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/-1 (Baseline) and Day 57/58

Population: PD population. Number of participants analyzed = participants with heart rate assessment at specified time-points.

The baseline value was the 24-hour mean on Day -2/-1 determined as overall, night and daytime mean. Measurements were made every 15 minutes from 07:00 to 23:00 (daytime) and every 30 minutes from 23:00 to 07:00 (night-time) at baseline and Day 57/58. Measurements were obtained after 10 minutes in the supine resting position.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=42 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 57/58 in 24-Hour Mean Heart Rate	3.34 beats per minute Standard Error 1.33	9.33 beats per minute Standard Error 1.24	9.17 beats per minute Standard Error 1.31

SECONDARY outcome

Timeframe: Every 15 minutes from 07:00 clock time to 23:00 clock time (day-time) and every 30 minutes from 23:00 clock time to 07:00 clock time (night-time) on Day -2/ -1 (Baseline) and Day 57/58

Population: PD population. Number of participants analyzed = participants with blood pressure assessment at specified time-points.

The baseline value was the 24-hour means on Day -2/-1 determined as overall, night and day-time mean. Measurements were made every 15 minutes from 07:00 to 23:00 (day-time) and every 30 minutes from 23:00 to 07:00 (night-time) at baseline and at Day 57/58. Measurements were obtained after 10 minutes in the supine resting position.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=42 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure 24-Hour Mean Systolic Blood Pressure	0.4 mmHg Standard Deviation 6.4	-0.5 mmHg Standard Deviation 7.1	-2.5 mmHg Standard Deviation 7.7
Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure 24-Hour Mean Diastolic Blood Pressure	0.8 mmHg Standard Deviation 4.1	2.4 mmHg Standard Deviation 4.7	1.6 mmHg Standard Deviation 4.7

SECONDARY outcome

Timeframe: 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to study drug administration on Day 57

Population: PD population. Number of participants analyzed = participants with body weight assessment at specified time-points.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 57 in Body Weight	-1.61 kg Standard Error 0.47	-1.78 kg Standard Error 0.48	-2.42 kg Standard Error 0.49

SECONDARY outcome

Timeframe: 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to IMP administration on Day 57

Population: PD population. Number of participants analyzed = participants with waist circumference assessment at specified time-points.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=43 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 57 in Waist Circumference	-1.40 cm Standard Deviation 4.66	-1.93 cm Standard Deviation 3.59	-2.12 cm Standard Deviation 4.95

SECONDARY outcome

Timeframe: 0.5 (8:00 clock time, prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours on Day -3; 0 (prior to standardized breakfast), 1.5, 2.5, 3.5, 4.5, 5.5 hours post study drug administration on Day 56

Population: PD population. Number of participants analyzed=participants with appetite perception assessment at specified time-points.

Visual Analogue Scale, 100 mm in length with words anchored at each end, expressing the most positive (100 mm) and the most negative rating (0 mm), was used to assess hunger, satiety, fullness and prospective food consumption. Responses were measured as distance from the left end of the line to the mark. Mean change from baseline was calculated for each parameter separately.

Outcome measures

Outcome measures
Measure	Lixisenatide 20 μg n=46 Participants Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=44 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=46 Participants Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast How hungry do you feel?	-3.7 mm Standard Deviation 16.4	-3.1 mm Standard Deviation 16.8	-1.0 mm Standard Deviation 14.6
Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast How satisfied do you feel?	4.5 mm Standard Deviation 15.8	8.9 mm Standard Deviation 13.2	3.6 mm Standard Deviation 11.0
Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast How full do you feel?	4.9 mm Standard Deviation 17.0	9.3 mm Standard Deviation 15.6	6.4 mm Standard Deviation 13.8
Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast How much do you think you can eat?	-6.4 mm Standard Deviation 16.1	-4.5 mm Standard Deviation 15.7	-7.2 mm Standard Deviation 12.0

Adverse Events

Lixisenatide 20 µg

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Liraglutide 1.2 mg

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Liraglutide 1.8 mg

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lixisenatide 20 µg n=48 participants at risk Subcutaneous injection of lixisenatide10 μg QD for 2 weeks followed by 20 μg QD for 6 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.2 mg n=47 participants at risk Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks, on top of insulin glargine with or without metformin.	Liraglutide 1.8 mg n=47 participants at risk Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks, on top of insulin glargine with or without metformin.
Cardiac disorders Coronary artery disease	2.1% 1/48 • All Adverse Events (AE) were collected from signature of the informed consent form up to the end of study (10 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (the time from the first drug injection \[included\] up to 3 days after the last injection of drug administration \[included\]).	0.00% 0/47 • All Adverse Events (AE) were collected from signature of the informed consent form up to the end of study (10 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (the time from the first drug injection \[included\] up to 3 days after the last injection of drug administration \[included\]).	0.00% 0/47 • All Adverse Events (AE) were collected from signature of the informed consent form up to the end of study (10 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (the time from the first drug injection \[included\] up to 3 days after the last injection of drug administration \[included\]).
Cardiac disorders Myocardial infarction	0.00% 0/48 • All Adverse Events (AE) were collected from signature of the informed consent form up to the end of study (10 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (the time from the first drug injection \[included\] up to 3 days after the last injection of drug administration \[included\]).	2.1% 1/47 • All Adverse Events (AE) were collected from signature of the informed consent form up to the end of study (10 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (the time from the first drug injection \[included\] up to 3 days after the last injection of drug administration \[included\]).	0.00% 0/47 • All Adverse Events (AE) were collected from signature of the informed consent form up to the end of study (10 weeks) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that developed/worsened during the 'on treatment period' (the time from the first drug injection \[included\] up to 3 days after the last injection of drug administration \[included\]).

Other adverse events

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 after trial completion, the Investigator can present or publish results. The investigator provides the sponsor with a copy of the presentation or publication for review and comment at least 30 days in advance of its submission. The sponsor can delay the submission for a period not exceeding 90 days to allow for filing a patent application or such other measures as sponsor deems appropriate to establish and preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER