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Efficacy and Safety of Lixisenatide Versus Insulin Glulisine on Top of Insulin Glargine With or Without Metformin in Type 2 Diabetic Patients (GetGoal-Duo-2)

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ClinicalTrials.gov Identifier: NCT01768559
Recruitment Status : Completed
First Posted : January 15, 2013
Results First Posted : January 4, 2017
Last Update Posted : January 4, 2017
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
Interventions Drug: Lixisenatide (AVE0010)
Drug: Insulin glulisine QD
Drug: Insulin glulisine TID
Drug: Insulin Glargine (Mandatory background drug)
Drug: Metformin (Background drug)
Enrollment 894
Recruitment Details The study was conducted at 199 centers in 18 countries. A total of 2159 participants were screened between January 08, 2013 and April 10, 2014.
Pre-assignment Details Participants underwent a 12-week run–in period with switch from other basal insulins to insulin glargine. A total of 1265 participants were screen failures/run-in failures; the most frequent reason for run-in failure was that glycosylated hemoglobin (HbA1c) criteria were not met at the end of run-in phase. 894 participants were randomized.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description Lixisenatide 10 mcg once daily (QD) subcutaneously (SC) for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. Insulin glulisine QD SC up to Week 26 on top of insulin glargine with or without metformin. Insulin glulisine thrice daily (TID) SC up to Week 26 on top of insulin glargine with or without metformin.
Period Title: Overall Study
Started 298 298 298
Treated 298 298 [1] 297 [2]
Completed 268 281 285
Not Completed 30 17 13
Reason Not Completed
Randomized but not treated             0             0             1
Adverse Event             15             2             5
Lack of Efficacy             6             4             0
Poor compliance to protocol             0             3             2
Other than specified             9             8             5
[1]
1 participant received Insulin Glulisine TID (for more than 50%)
[2]
4 participants received Insulin Glulisine QD (for more than 50%)
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID Total
Hide Arm/Group Description Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin. Insulin glulisine QD SC up to Week 26 on top of insulin glargine with or without metformin. Insulin glulisine TID SC up to Week 26 on top of insulin glargine with or without metformin. Total of all reporting groups
Overall Number of Baseline Participants 298 298 298 894
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 298 participants 298 participants 298 participants 894 participants
59.8  (8.6) 60.2  (8.6) 59.4  (9.5) 59.8  (8.9)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 298 participants 298 participants 298 participants 894 participants
Female
160
  53.7%
163
  54.7%
166
  55.7%
489
  54.7%
Male
138
  46.3%
135
  45.3%
132
  44.3%
405
  45.3%
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 298 participants 298 participants 298 participants 894 participants
Caucasian/White 276 280 272 828
Black 13 11 12 36
Asian/Oriental 9 7 13 29
Other 0 0 1 1
Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 298 participants 298 participants 298 participants 894 participants
Hispanic 63 58 68 189
Non-Hispanic 235 240 230 705
Metformin Use at Screening  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 298 participants 298 participants 298 participants 894 participants
Yes 262 260 259 781
No 36 38 39 113
Number of Participants with Categorical Body Mass Index (BMI)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 298 participants 298 participants 298 participants 894 participants
<30 kg/m^2 97 118 97 312
≥30 kg/m^2 201 180 200 581
Participants not analyzed for BMI 0 0 1 1
BMI   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 298 participants 298 participants 298 participants 894 participants
32.27  (4.57) 31.86  (4.39) 32.50  (4.60) 32.21  (4.52)
[1]
Measure Description: 893 participants (298 in Lixisenatide arm; 298 in Insulin glulisine QD and 297 in Insulin glulisine TID) were included for baseline BMI analysis.
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 298 participants 298 participants 298 participants 894 participants
90.06  (17.31) 88.45  (15.84) 90.08  (17.18) 89.53  (16.79)
[1]
Measure Description: 893 participants (298 in Lixisenatide arm, 298 in Insulin glulisine QD and 297 in Insulin glulisine TID) were included for baseline weight analysis.
HbA1c   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of hemoglobin
Number Analyzed 298 participants 298 participants 298 participants 894 participants
7.77  (0.55) 7.73  (0.59) 7.79  (0.60) 7.76  (0.58)
[1]
Measure Description: 893 participants (298 in Lixisenatide arm; 298 in Insulin glulisine QD and 297 in Insulin glulisine TID) were included for HbA1c analysis.
Fasting Plasma Glucose (FPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 298 participants 298 participants 298 participants 894 participants
6.58  (1.82) 6.84  (1.98) 6.65  (1.89) 6.69  (1.90)
[1]
Measure Description: 893 participants (298 in Lixisenatide arm; 298 in Insulin glulisine QD and 297 in Insulin glulisine TID) were included for FPG analysis.
2-Hour Postprandial Plasma Glucose (PPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 298 participants 298 participants 298 participants 894 participants
14.26  (3.55) 14.02  (3.59) 14.25  (3.35) 14.18  (3.47)
[1]
Measure Description: 258 participants (79 in Lixisenatide arm; 77 in Insulin glulisine QD and 102 in Insulin glulisine TID) were included for PPG analysis.
2-Hour Glucose Excursion   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 298 participants 298 participants 298 participants 894 participants
7.31  (3.19) 7.31  (3.63) 7.35  (3.34) 7.33  (3.37)
[1]
Measure Description: 243 participants (73 in Lixisenatide arm, 74 in Insulin glulisine QD and 96 in Insulin glulisine TID) were included for 2-hour glucose excursion analysis.
Average 7-Point Self-monitored Plasma Glucose (SMPG)   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 298 participants 298 participants 298 participants 894 participants
9.02  (1.75) 9.07  (1.74) 8.99  (1.57) 9.02  (1.68)
[1]
Measure Description: 877 participants (292 in Lixisenatide arm; 291 in Insulin glulisine QD and 294 in Insulin glulisine TID) were included for average 7-point SMPG analysis.
Insulin Glargine Dose   [1] 
Mean (Standard Deviation)
Unit of measure:  Units (U)
Number Analyzed 298 participants 298 participants 298 participants 894 participants
67.25  (31.95) 64.72  (32.07) 64.97  (26.90) 65.65  (30.39)
[1]
Measure Description: 893 participants (298 in Lixisenatide arm; 298 in Insulin glulisine QD and 297 in Insulin glulisine TID) were included for Insulin glargine dose analysis.
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 298 participants 298 participants 298 participants 894 participants
11.89  (6.43) 12.33  (6.75) 12.41  (6.80) 12.21  (6.66)
1.Primary Outcome
Title Change in HbA1c From Baseline to Week 26
Hide Description Change in HbA1C was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last on-treatment 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.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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 efficacy assessment, irrespective of compliance with study protocol/procedures.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 292 292 295
Least Squares Mean (Standard Error)
Unit of Measure: percentage of hemoglobin
-0.63  (0.054) -0.58  (0.054) -0.84  (0.053)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lixisenatide, Insulin Glulisine QD
Comments Analysis was performed using analysis of covariance (ANCOVA) model with treatment groups, strata of Week -1 HbA1c (<8.0, ≥8.0%), randomization strata of metformin use, and country as fixed effects and baseline HbA1c value as a covariate. The non-inferiority was assessed using upper bound of 2-sided 95% Confidence Interval (CI).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Pre-specified non-inferiority margin of 0.4%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean Difference
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.17 to 0.064
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.059
Estimation Comments Lixisenatide vs Insulin Glulisine QD
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lixisenatide, Insulin Glulisine TID
Comments Analysis was performed using ANCOVA model as described above. Hochberg procedure was used to control type 1 error at significance level = 0.025 (1-sided) for comparison between Lixisenatide vs Insulin glulisine TID in HbA1c and body weight. If both comparisons were met, then both would be declared significant. Otherwise, if only one was met, then the one met should be tested at α=0.0125 (1-sided).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Pre-specified non-inferiority margin of 0.4%.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.095 to 0.328
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.059
Estimation Comments Lixisenatide vs Insulin Glulisine TID
2.Primary Outcome
Title Change in Body Weight From Baseline to Week 26
Hide Description

Primary outcome was the comparison between Lixisenatide versus Insulin Glulisine TID.

Change in body weight was calculated by subtracting baseline value from Week 26 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.

Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 295 295 295
Least Squares Mean (Standard Error)
Unit of Measure: kg
-0.63  (0.276) 1.03  (0.276) 1.37  (0.271)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lixisenatide, Insulin Glulisine TID
Comments Analysis was performed using ANCOVA model as described above. Hochberg procedure was used to control type 1 error at α = 0.025 (1-sided) for comparison between lixisenatide vs insulin glulisine TID in HbA1c and body weight. If both comparisons were met, then both would be declared significant. Otherwise, if only one was met, then the one met should be tested at α=0.0125 (1-sided).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments Threshold for significance at 0.025 level.
Method ANCOVA
Comments The superiority was assessed by comparing the P-value at significance level = 0.025 or 0.0125.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-2.593 to -1.396
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.305
Estimation Comments Lixisenatide vs Insulin Glulisine TID
3.Secondary Outcome
Title Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26
Hide Description The 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. Missing data was imputed using LOCF.
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline HbA1c assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 292 292 295
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c ≤6.5% 20.5 17.8 30.8
HbA1c <7.0% 42.1 38.4 49.2
4.Secondary Outcome
Title Percentage of Participants With no Weight Gain at Week 26
Hide Description The on-treatment period for this efficacy variable was the time from the first dose of study drug up to 3 days after the last dose of study drug.
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline body weight assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 295 295 295
Measure Type: Number
Unit of Measure: percentage of participants
64.7 36.6 30.5
5.Secondary Outcome
Title Change in Average 7-point SMPG Profiles From Baseline to Week 26
Hide Description Participants recorded a 7-point plasma glucose profile measured before and 2 hours after each meal and at bedtime three times in a week before baseline, before visit Week 12 and before visit week 26 and 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 26 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.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline 7-point SMPG assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 270 268 278
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.784  (0.1141) -0.782  (0.1133) -1.053  (0.1105)
6.Secondary Outcome
Title Change in FPG From Baseline to Week 26
Hide Description Change in FPG was calculated by subtracting baseline value from Week 26 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.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline FPG assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 295 295 294
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-0.23  (0.143) -0.21  (0.142) -0.06  (0.14)
7.Secondary Outcome
Title Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast)
Hide Description The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change in PPG was calculated by subtracting baseline value from Week 26 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 the day of last dose of study drug.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with IMP injection before breakfast and baseline and at least one post-baseline 2-hour PPG assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 69 55 68
Mean (Standard Deviation)
Unit of Measure: mmol/L
-3.93  (4.29) -1.62  (4.01) -1.87  (3.18)
8.Secondary Outcome
Title Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast)
Hide Description Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change in glucose excursions was calculated by subtracting baseline value from Week 26 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 the day of last dose of study drug.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with IMP injection before breakfast and baseline and at least one post-baseline glucose excursion assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 64 53 66
Mean (Standard Deviation)
Unit of Measure: mmol/L
-3.42  (4.13) -1.59  (3.42) -1.56  (2.52)
9.Secondary Outcome
Title Change in Insulin Glargine Dose From Baseline to Week 26
Hide Description Change in Insulin glargine dose was calculated by subtracting the baseline value from Week 26 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 the day of last dose of study drug.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline insulin glargine dose assessment during on-treatment period.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 292 294 294
Least Squares Mean (Standard Error)
Unit of Measure: U
0.7  (1.002) -0.06  (0.999) -3.13  (0.982)
10.Secondary Outcome
Title Insulin Glulisine Dose at Week 26
Hide Description The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF.
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline insulin glulisine dose assessment during on-treatment period.
Arm/Group Title Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 295 293
Mean (Standard Deviation)
Unit of Measure: U
9.97  (7.8) 20.24  (13.04)
11.Secondary Outcome
Title Total Insulin Dose at Week 26
Hide Description

The on-treatment period for this efficacy variable was the time from the first dose of study drug up to the day of last dose of study drug. Missing data was imputed using LOCF.

The outcome is reporting results of total insulin (amounts of Insulin Glargine plus Insulin Glulisine ) only for the arms in which Insulin Glulisine was administered and is not applicable for the lixisenatide arm in which only Insulin Glargine is administered. Change in dose of the insulin used by patients in the Lixisenatide arm (i.e. Insulin Glargine) is reported in the secondary Outcome Measure 9.

Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. Here, number of participants analyzed = participants with baseline and at least one post-baseline total insulin dose assessment during on-treatment period.
Arm/Group Title Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 295 294
Mean (Standard Deviation)
Unit of Measure: U
73.61  (39.13) 81.05  (33.55)
12.Secondary Outcome
Title Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia
Hide Description Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <60 mg/dL (3.3 mmol/L). Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the participant required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available.
Time Frame First dose of study drug up to 3 days after the last dose administration (maximum of 185 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All randomized participants who were exposed to at least one dose of study drug, regardless of the amount of treatment administered.

The 4 participants in the TID group who received Insulin Glulisine QD were analyzed according to the QD dose.The 1 participant in the QD group who received Insulin Glulisine TID was analyzed according to the TID dose

Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 298 301 294
Measure Type: Number
Unit of Measure: percentage of participants
Documented symptomatic hypoglycemia 31.5 37.5 44.6
Severe symptomatic hypoglycemia 0 0.7 0
13.Secondary Outcome
Title Percentage of Participants Who Reached the Target of HbA1c <7% at Week 26 and Did Not Experienced Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26 Week Treatment Period
Hide Description The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug.
Time Frame Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population. 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.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 296 293 295
Measure Type: Number
Unit of Measure: percentage of participants
29.4 24.2 26.1
14.Secondary Outcome
Title Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26
Hide Description The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug.
Time Frame Week 26
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Hide Analysis Population Description
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 non-response. Otherwise, they were counted as missing data.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin.
Overall Number of Participants Analyzed 295 293 295
Measure Type: Number
Unit of Measure: percentage of participants
31.2 16.7 17.6
15.Secondary Outcome
Title Percentage of Participants Who Reached the Target of HbA1c <7%, Had no Weight Gain at Week 26, and Did Not Experience Documented (Plasma Glucose <60 mg/dL) Symptomatic Hypoglycemia During 26-Week Treatment Period
Hide Description The on-treatment period for HbA1c assessment was defined as the time from the first dose of study drug up to 14 days after the last dose of study drug. The on-treatment period for body weight assessment was defined as the time from the first dose of study drug up to 3 days after the last dose of study drug. The on-treatment period for symptomatic hypoglycemia assessment was defined as the time from the first dose of study drug up to 1 day after the last dose of study drug. Participants without post-baseline on-treatment values (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 non-response, or if they experienced at least one documented symptomatic hypoglycemia during the on-treatment period. Otherwise, they were counted as missing data.
Time Frame Week 26
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Hide Analysis Population Description
mITT population.Participants without post-baseline on-treatment values(HbA1c;body weight),no more than 30 days apart counted as non-responders if at least one of components(HbA1c;body weight) was available,showed non-response or experienced at least one symptomatic hypoglycemia during on-treatment period.Otherwise,they were counted as missing data.
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description:
Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine QD SC up to Week 26 on top of insulin glargine with or without metformin.
Insulin glulisine TID SC up to Week 26 on top of insulin glargine with or without metformin.
Overall Number of Participants Analyzed 297 294 295
Measure Type: Number
Unit of Measure: percentage of participants
22.2 9.2 10.8
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Day 185) regardless of seriousness or relationship to IMP.
Adverse Event Reporting Description

Reported AEs are treatment-emergent adverse events that is AEs 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). Analysis was done on safety population.

4 participants randomized to TID group, but received insulin glulisine QD were analyzed according to the QD dose. 1 participant randomized to QD group, but received insulin glulisine TID was analyzed according to the TID dose.

 
Arm/Group Title Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Hide Arm/Group Description Lixisenatide 10 mcg QD SC for 2 weeks, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin (Median exposure of 182 days). Insulin glulisine QD SC up to Week 26 on top of Insulin glargine with or without metformin (Median exposure of 182 days). Insulin glulisine TID SC up to Week 26 on top of Insulin glargine with or without metformin (Median exposure of 182 days).
All-Cause Mortality
Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/298 (3.69%)   11/301 (3.65%)   14/294 (4.76%) 
Cardiac disorders       
Angina pectoris  1  1/298 (0.34%)  0/301 (0.00%)  1/294 (0.34%) 
Angina unstable  1  0/298 (0.00%)  1/301 (0.33%)  0/294 (0.00%) 
Atrial fibrillation  1  0/298 (0.00%)  1/301 (0.33%)  0/294 (0.00%) 
Atrioventricular block complete  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Cardiac failure chronic  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Cardiac failure congestive  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Myocardial infarction  1  0/298 (0.00%)  1/301 (0.33%)  0/294 (0.00%) 
Myocardial ischaemia  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Gastrointestinal disorders       
Abdominal pain  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Epigastric discomfort  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Gastric ulcer haemorrhage  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Hepatobiliary disorders       
Hepatic mass  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Infections and infestations       
Erysipelas  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Penile infection  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Septic arthritis staphylococcal  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Cellulitis  1  0/298 (0.00%)  1/301 (0.33%)  1/294 (0.34%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  0/298 (0.00%)  2/301 (0.66%)  1/294 (0.34%) 
Ankle fracture  1  0/298 (0.00%)  1/301 (0.33%)  0/294 (0.00%) 
Incisional hernia  1  0/298 (0.00%)  1/301 (0.33%)  0/294 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Dehydration  1  1/298 (0.34%)  1/301 (0.33%)  0/294 (0.00%) 
Hypoglycaemia  1  0/298 (0.00%)  1/301 (0.33%)  0/294 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Invasive ductal breast carcinoma  1  1/298 (0.34%)  0/301 (0.00%)  1/294 (0.34%) 
Pancreatic carcinoma metastatic  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Uterine cancer  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Basal cell carcinoma  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Neoplasm malignant  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Nervous system disorders       
Cerebrovascular accident  1  1/298 (0.34%)  0/301 (0.00%)  2/294 (0.68%) 
Hypoglycaemic unconsciousness  1  0/298 (0.00%)  2/301 (0.66%)  0/294 (0.00%) 
Neuritis cranial  1  0/298 (0.00%)  1/301 (0.33%)  0/294 (0.00%) 
Renal and urinary disorders       
Renal failure  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Renal failure acute  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Skin and subcutaneous tissue disorders       
Diabetic bullosis  1  1/298 (0.34%)  0/301 (0.00%)  0/294 (0.00%) 
Skin ulcer haemorrhage  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Vascular disorders       
Hypertension  1  0/298 (0.00%)  0/301 (0.00%)  1/294 (0.34%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lixisenatide Insulin Glulisine QD Insulin Glulisine TID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   183/298 (61.41%)   186/301 (61.79%)   195/294 (66.33%) 
Gastrointestinal disorders       
Nausea  1  75/298 (25.17%)  5/301 (1.66%)  3/294 (1.02%) 
Vomiting  1  26/298 (8.72%)  5/301 (1.66%)  6/294 (2.04%) 
Diarrhoea  1  20/298 (6.71%)  10/301 (3.32%)  4/294 (1.36%) 
Infections and infestations       
Nasopharyngitis  1  14/298 (4.70%)  21/301 (6.98%)  18/294 (6.12%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  0/298 (0.00%)  12/301 (3.99%)  20/294 (6.80%) 
Investigations       
Blood glucose decreased  1  60/298 (20.13%)  67/301 (22.26%)  82/294 (27.89%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  107/298 (35.91%)  140/301 (46.51%)  154/294 (52.38%) 
Nervous system disorders       
Headache  1  20/298 (6.71%)  8/301 (2.66%)  12/294 (4.08%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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 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.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01768559     History of Changes
Other Study ID Numbers: EFC12626
2012-004096-38 ( EudraCT Number )
U1111-1131-4936 ( Other Identifier: UTN )
First Submitted: January 11, 2013
First Posted: January 15, 2013
Results First Submitted: August 22, 2016
Results First Posted: January 4, 2017
Last Update Posted: January 4, 2017