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

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ClinicalTrials.gov Identifier: NCT01596504
Recruitment Status : Completed
First Posted : May 11, 2012
Results First Posted : October 14, 2016
Last Update Posted : October 14, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: Lixisenatide (AVE0010)
Drug: Liraglutide
Drug: Insulin Glargine
Drug: Metformin
Enrollment 142
Recruitment Details The study was conducted at 8 centers in Germany between 22 May 2012 to 25 July 2013.
Pre-assignment Details A total of 236 participants were screened and 142 participants were randomized and treated.
Arm/Group Title Lixisenatide 20 μg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 48 47 47
Completed 46 44 46
Not Completed 2 3 1
Reason Not Completed
Participant's Private Reason             0             1             0
Adverse Event             1             2             1
Withdrawal by Subject             1             0             0
Arm/Group Title Lixisenatide 20 μg Liraglutide 1.2 mg Liraglutide 1.8 mg Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 48 47 47 142
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 47 participants 47 participants 142 participants
61.6  (7.4) 61.4  (7.9) 62.6  (9.4) 61.9  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 47 participants 47 participants 142 participants
Female
15
  31.3%
8
  17.0%
14
  29.8%
37
  26.1%
Male
33
  68.8%
39
  83.0%
33
  70.2%
105
  73.9%
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 47 participants 47 participants 142 participants
Caucasian/White 48 46 47 141
Other 0 1 0 1
Metformin Use at Screening  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 47 participants 47 participants 142 participants
Yes 43 41 41 125
No 5 6 6 17
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 48 participants 47 participants 47 participants 142 participants
90.56  (13.09) 91.62  (13.92) 92.92  (15.33) 91.69  (14.07)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  (kg/m²)
Number Analyzed 48 participants 47 participants 47 participants 142 participants
30.68  (4.34) 30.52  (4.01) 31.17  (4.34) 30.79  (4.22)
HbA1c at Screening (Day -7)  
Mean (Standard Deviation)
Unit of measure:  Percentage of haemoglobin
Number Analyzed 48 participants 47 participants 47 participants 142 participants
7.22  (0.48) 7.19  (0.53) 7.33  (0.5) 7.25  (0.50)
1.Primary Outcome
Title 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
Hide Description 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).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Lixisenatide 20 μg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 43 45
Least Squares Mean (Standard Error)
Unit of Measure: h*mmol/L
-13.33  (1.11) -7.32  (1.12) -8.72  (1.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lixisenatide 20 μg, Liraglutide 1.2 mg
Comments Analysis was performed using linear fixed effects model with treatment groups and stratification factors (HbA1c levels on Day -7 [<8% and >=8%], use of metformin at screening [yes or no]) and the study site) as fixed effects and baseline plasma glucose AUC from 0.5 to 4.5 hours as covariate. To address multiplicity issue and ensure overall 1-sided level of 5%, Hochberg method was used for testing procedure of comparison between lixisenatide vs liraglutide 1.2 mg or 1.8 mg.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-values ordered(p1≤p2) as per rules:if p2≤0.05: lixisenatide superior to liraglutide (both doses);if p2>0.05 & p1≤0.025:lixisenatide superior to dose of liraglutide associated with p1;if p2>0.05 & p1>0.025:no comparison as statistically significant.
Method Linear fixed effects model
Comments The threshold for significance at 0.05 level.
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value -6.01
Confidence Interval (1-Sided) 95%
-7.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.06
Estimation Comments Lixisenatide vs Liraglutide 1.2 mg
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lixisenatide 20 μg, Liraglutide 1.8 mg
Comments Analysis was performed using linear mixed effects model with treatment groups and stratification factors (HbA1c levels on Day -7 [<8% and >=8%], use of metformin at screening [yes or no]), and the study site) as fixed effects and baseline plasma glucose AUC from 0.5 to 4.5 hours as covariate. To address multiplicity issue and ensure overall 1-sided level of 5%, Hochberg method was used for testing procedure of comparison between lixisenatide vs liraglutide 1.2 mg or 1.8 mg.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-values ordered(p1≤p2) as per rules:if p2≤0.05:lixisenatide superior to liraglutide (both doses);if p2>0.05 & p1≤0.025:lixisenatide superior to dose of liraglutide associated with p1;if p2>0.05 & p1>0.025: no comparison as statistically significant.
Method Linear fixed effects model
Comments The threshold for significance at 0.05 level.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.61
Confidence Interval (1-Sided) 95%
-6.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.04
Estimation Comments Lixisenatide vs Liraglutide 1. 8 mg
2.Secondary Outcome
Title Change From Baseline to Day 56 in Plasma Glucose Corrected AUC From Time 0.5 Hours to 5.5 Hours
Hide Description 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).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 43 45
Least Squares Mean (Standard Error)
Unit of Measure: h*mmol/L
-13.82  (1.19) -9.09  (1.21) -10.33  (1.25)
3.Secondary Outcome
Title Number of Participants With 2-Hour Post-prandial Plasma Glucose (PPG) <7.77 (mmol/L) at Day 56
Hide Description 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.
Time Frame Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Measure Type: Number
Unit of Measure: participants
35 13 11
4.Secondary Outcome
Title Change From Baseline to Day 56 in PPG Excursion
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 43 45
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-3.26  (0.4) -1.79  (0.4) -2.5  (0.42)
5.Secondary Outcome
Title Change From Baseline to Day 56 in Fasting Plasma Glucose (FPG)
Hide Description 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.
Time Frame 0.5 hour (prior to standardized breakfast) on Day -3; 0.5 hour (prior to standardized breakfast) on Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with plasma glucose assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 45 44 45
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
0.1  (0.22) 0.12  (0.22) 0.13  (0.23)
6.Secondary Outcome
Title Change From Baseline to Day 56 in Average 7-Point Self-Monitored Plasma Glucose (SMPG)
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with 7 point SMPG assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.69  (1.19) -0.76  (1.23) -1.2  (1.09)
7.Secondary Outcome
Title Change From Baseline to Day 56 in Corrected C-Peptide AUC From Time 0.5 Hours to 5.5 Hours
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with C-peptide assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 43 45
Least Squares Mean (Standard Error)
Unit of Measure: h*nmol/L
-1.16  (0.37) 1.23  (0.37) 0.88  (0.39)
8.Secondary Outcome
Title Change From Baseline to Day 56 in Corrected Glucagon AUC From Time 0.5 Hours to 5.5 Hours
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with glucagon assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 43 45
Least Squares Mean (Standard Error)
Unit of Measure: h*ng/L
-16.56  (19.43) 11.58  (19.86) 5.6  (20.3)
9.Secondary Outcome
Title Change From Baseline to Day 56 in HbA1c
Hide Description HbA1C was assessed using the high performance liquid chromatography method.
Time Frame Pre-dose (Hour 0) on Day 1 (Baseline) and Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed = participants with HbA1c assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-0.58  (0.06) -0.66  (0.06) -0.74  (0.06)
10.Secondary Outcome
Title Change From Baseline to Day 56 in Average Daily Insulin Glargine Dose
Hide Description [Not Specified]
Time Frame Day -7 (Baseline), Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed=participants with insulin glargine dose assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Mean (Standard Deviation)
Unit of Measure: units
-4.7  (4.8) -4.6  (6.8) -4.0  (6.5)
11.Secondary Outcome
Title Change From Baseline to Day 55 in Gastric Emptying Half Life (t1/2)
Hide Description Gastric emptying was measured using 13C-octanoic acid breath test by isotope-selective non-dispersive infrared spectrometry.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed=participants with gastric emptying assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Least Squares Mean (Standard Error)
Unit of Measure: minutes (min)
453.56  (58.24) 175.31  (58.49) 130.49  (60.27)
12.Secondary Outcome
Title Change From Baseline to Day 55 in Gastric Emptying Coefficient
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with gastric emptying at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Mean (Standard Deviation)
Unit of Measure: coefficient (unit-less)
-0.33  (1.09) -0.34  (0.53) -0.28  (0.52)
13.Secondary Outcome
Title Change From Baseline to Day 57/58 in 24-Hour Mean Heart Rate
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with heart rate assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 42 43 44
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute
3.34  (1.33) 9.33  (1.24) 9.17  (1.31)
14.Secondary Outcome
Title Change From Baseline to Day 57/58 in 24-Hour Mean Systolic Blood Pressure and Diastolic Blood Pressure
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed = participants with blood pressure assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 42 43 44
Mean (Standard Deviation)
Unit of Measure: mmHg
24-Hour Mean Systolic Blood Pressure 0.4  (6.4) -0.5  (7.1) -2.5  (7.7)
24-Hour Mean Diastolic Blood Pressure 0.8  (4.1) 2.4  (4.7) 1.6  (4.7)
15.Secondary Outcome
Title Change From Baseline to Day 57 in Body Weight
Hide Description [Not Specified]
Time Frame 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to study drug administration on Day 57
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Hide Analysis Population Description
PD population. Number of participants analyzed = participants with body weight assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Least Squares Mean (Standard Error)
Unit of Measure: kg
-1.61  (0.47) -1.78  (0.48) -2.42  (0.49)
16.Secondary Outcome
Title Change From Baseline to Day 57 in Waist Circumference
Hide Description [Not Specified]
Time Frame 0.5 hours prior to standardized breakfast on Day -1 (Baseline); 0.5 hours prior to IMP administration on Day 57
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Hide Analysis Population Description
PD population. Number of participants analyzed = participants with waist circumference assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 43 46
Mean (Standard Deviation)
Unit of Measure: cm
-1.40  (4.66) -1.93  (3.59) -2.12  (4.95)
17.Secondary Outcome
Title Change From Baseline to Day 56 in the Cumulative Score Mean on the Appetite Perception Using a Visual Analogue Scale After Standardized Solid Breakfast
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PD population. Number of participants analyzed=participants with appetite perception assessment at specified time-points.
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 46 44 46
Mean (Standard Deviation)
Unit of Measure: mm
How hungry do you feel? -3.7  (16.4) -3.1  (16.8) -1.0  (14.6)
How satisfied do you feel? 4.5  (15.8) 8.9  (13.2) 3.6  (11.0)
How full do you feel? 4.9  (17.0) 9.3  (15.6) 6.4  (13.8)
How much do you think you can eat? -6.4  (16.1) -4.5  (15.7) -7.2  (12.0)
Time Frame 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.
Adverse Event Reporting Description 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]).
 
Arm/Group Title Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/48 (2.08%)   1/47 (2.13%)   0/47 (0.00%) 
Cardiac disorders       
Coronary artery disease  1  1/48 (2.08%)  0/47 (0.00%)  0/47 (0.00%) 
Myocardial infarction  1  0/48 (0.00%)  1/47 (2.13%)  0/47 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lixisenatide 20 µg Liraglutide 1.2 mg Liraglutide 1.8 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   26/48 (54.17%)   27/47 (57.45%)   27/47 (57.45%) 
Gastrointestinal disorders       
Abdominal distension  1  3/48 (6.25%)  7/47 (14.89%)  4/47 (8.51%) 
Abdominal pain  1  2/48 (4.17%)  3/47 (6.38%)  1/47 (2.13%) 
Abdominal pain upper  1  1/48 (2.08%)  0/47 (0.00%)  5/47 (10.64%) 
Constipation  1  0/48 (0.00%)  5/47 (10.64%)  3/47 (6.38%) 
Diarrhoea  1  3/48 (6.25%)  4/47 (8.51%)  5/47 (10.64%) 
Dyspepsia  1  3/48 (6.25%)  3/47 (6.38%)  4/47 (8.51%) 
Flatulence  1  2/48 (4.17%)  0/47 (0.00%)  4/47 (8.51%) 
Nausea  1  9/48 (18.75%)  8/47 (17.02%)  11/47 (23.40%) 
Vomiting  1  5/48 (10.42%)  2/47 (4.26%)  5/47 (10.64%) 
General disorders       
Fatigue  1  3/48 (6.25%)  1/47 (2.13%)  4/47 (8.51%) 
Malaise  1  3/48 (6.25%)  0/47 (0.00%)  1/47 (2.13%) 
Infections and infestations       
Nasopharyngitis  1  6/48 (12.50%)  10/47 (21.28%)  5/47 (10.64%) 
Metabolism and nutrition disorders       
Decreased appetite  1  9/48 (18.75%)  9/47 (19.15%)  13/47 (27.66%) 
Nervous system disorders       
Dizziness postural  1  3/48 (6.25%)  1/47 (2.13%)  0/47 (0.00%) 
Headache  1  4/48 (8.33%)  5/47 (10.64%)  8/47 (17.02%) 
Psychiatric disorders       
Insomnia  1  0/48 (0.00%)  0/47 (0.00%)  3/47 (6.38%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01596504     History of Changes
Other Study ID Numbers: PDY12625
2012-000027-40 ( EudraCT Number )
U1111-1124-1364 ( Other Identifier: UTN )
First Submitted: May 7, 2012
First Posted: May 11, 2012
Results First Submitted: August 22, 2016
Results First Posted: October 14, 2016
Last Update Posted: October 14, 2016