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)

A Randomized, Open-label, Active-controlled, 3-arm Parallel-group, 26-week Study Comparing the Efficacy and Safety of Lixisenatide to That of Insulin Glulisine Once Daily and Insulin Glulisine Three Times Daily in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine With or Without Metformin

Primary Objective:

- To compare lixisenatide versus insulin glulisine in terms of glycosylated hemoglobin (HbA1c) reduction and body weight change at Week 26 in type 2 diabetic participants not adequately controlled on insulin glargine ± metformin.

Secondary Objectives:

- To compare the treatments/regimens on:

• The percentage of participants reaching the target of HbA1c <7% or ≤6.5%,
• Body weight,
• Self-Monitored Glucose profiles,
• Fasting Plasma Glucose (FPG),
• Post-prandial plasma glucose (PPG) /glucose excursions during a standardized meal test (subset of participants),
• Daily doses of insulins,
• Safety and tolerability.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Lixisenatide (AVE0010); Drug: Insulin Glargine (Mandatory background drug); Drug: Metformin (Background drug); Drug: Insulin glulisine QD; Drug: Insulin glulisine TID

Detailed Description

Approximately 41 weeks including a 26 week treatment period.

• Study Type: Interventional
• Enrollment (Actual): 894
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Brampton, Canada, L6R 3J5
    • Investigational Site Number 124008
  • Burlington, Canada, L7M 4Y1
    • Investigational Site Number 124015
  • Chatham, Canada, N7L 1C1
    • Investigational Site Number 124018
  • Coquitlam, Canada, V3K 3P4
    • Investigational Site Number 124004
  • Etobicoke, Canada, M9R 4E1
    • Investigational Site Number 124016
  • Hamilton, Canada, L8L 5G8
    • Investigational Site Number 124014
  • Montreal, Canada, H1Y 3L1
    • Investigational Site Number 124020
  • Montreal, Canada, H3A 1A1
    • Investigational Site Number 124011
  • Newmarket, Canada, L3Y 5G8
    • Investigational Site Number 124017
  • Quebec, Canada, G1N 4V3
    • Investigational Site Number 124021
  • Red Deer, Canada, T4N 6V7
    • Investigational Site Number 124003
  • Sherbrooke, Canada, J1H 5N4
    • Investigational Site Number 124002
  • St-Romuald, Canada, G6W 5M6
    • Investigational Site Number 124012
  • Toronto, Canada, M4G 3E8
    • Investigational Site Number 124001
  • Toronto, Canada, M5C 2T2
    • Investigational Site Number 124010
  • Vancouver, Canada, V5Z 1M9
    • Investigational Site Number 124005
  • Victoria, Canada, V8V 4A1
    • Investigational Site Number 124006
  • Winnipeg, Canada, R3E 3P4
    • Investigational Site Number 124007
• Chile
  • Santiago, Chile, 7500010
    • Investigational Site Number 152103
  • Santiago, Chile, 7500347
    • Investigational Site Number 152107
  • Santiago, Chile, 7500710
    • Investigational Site Number 152101
  • Santiago, Chile, 7591047
    • Investigational Site Number 152105
  • Santiago, Chile, 7980378
    • Investigational Site Number 152102
  • Santiago, Chile, 8053095
    • Investigational Site Number 152106
  • Santiago, Chile, 8053095
    • Investigational Site Number 152108
  • Santiago, Chile
    • Investigational Site Number 152109
• Czech Republic
  • Beroun, Czech Republic, 26601
    • Investigational Site Number 203107
  • Jilove U Prahy, Czech Republic, 254 01
    • Investigational Site Number 203103
  • Ostrava 2, Czech Republic, 702 00
    • Investigational Site Number 203101
  • Police Nad Metuji, Czech Republic, 549 54
    • Investigational Site Number 203110
  • Praha 4, Czech Republic, 14021
    • Investigational Site Number 203105
  • Praha 4, Czech Republic, 148 00
    • Investigational Site Number 203102
  • Praha 4, Czech Republic, 14900
    • Investigational Site Number 203108
  • Trutnov, Czech Republic, 54101
    • Investigational Site Number 203104
• Estonia
  • Pärnu, Estonia, 80018
    • Investigational Site Number 233102
  • Tallinn, Estonia, 13415
    • Investigational Site Number 233103
  • Tallinn, Estonia, 13419
    • Investigational Site Number 233104
  • Viljandimaa, Estonia, 71024
    • Investigational Site Number 233101
• France
  • Bois Guillaume, France, 76230
    • Investigational Site Number 250108
  • Corbeil Essonnes, France, 91100
    • Investigational Site Number 250105
  • La Rochelle Cedex, France, 17019
    • Investigational Site Number 250104
  • Lyon, France, 69495
    • Investigational Site Number 250106
  • Lyon, France, 69495
    • Investigational Site Number 250107
  • Mantes La Jolie, France, 78200
    • Investigational Site Number 250109
  • Paris Cedex 15, France, 75908
    • Investigational Site Number 250102
  • Vandoeuvre Les Nancy, France, 54511
    • Investigational Site Number 250101
  • Venissieux, France, 69200
    • Investigational Site Number 250103
• Germany
  • Bad Mergentheim, Germany, 97980
    • Investigational Site Number 276112
  • Berlin, Germany, 13125
    • Investigational Site Number 276108
  • Dortmund, Germany, 44137
    • Investigational Site Number 276102
  • Dresden, Germany, 01067
    • Investigational Site Number 276120
  • Dresden, Germany, 01307
    • Investigational Site Number 276106
  • Frankfurt A.M., Germany, 60596
    • Investigational Site Number 276117
  • Görlitz, Germany, 02826
    • Investigational Site Number 276116
  • Heidelberg, Germany, 69115
    • Investigational Site Number 276113
  • Leipzig, Germany, 04103
    • Investigational Site Number 276118
  • Magdeburg, Germany, 39104
    • Investigational Site Number 276119
  • Neumünster, Germany, 24534
    • Investigational Site Number 276103
  • Speyer, Germany, 67346
    • Investigational Site Number 276115
  • St. Ingbert-Oberwürzbach, Germany, 66386
    • Investigational Site Number 276109
• Hungary
  • Budapest, Hungary, 1134
    • Investigational Site Number 348107
  • Budapest, Hungary, 1138
    • Investigational Site Number 348108
  • Budapest, Hungary, 1139
    • Investigational Site Number 348102
  • Eger, Hungary, 3300
    • Investigational Site Number 348101
  • Pápa, Hungary, 8500
    • Investigational Site Number 348103
  • Szeged, Hungary, 6720
    • Investigational Site Number 348104
  • Sátoraljaújhely, Hungary, 3980
    • Investigational Site Number 348106
  • Zalaegerszeg, Hungary, 8900
    • Investigational Site Number 348105
• Italy
  • Bologna, Italy, 40138
    • Investigational Site Number 380103
  • Catania, Italy, 95122
    • Investigational Site Number 380102
  • Milano, Italy, 20132
    • Investigational Site Number 380101
  • Napoli, Italy, 80131
    • Investigational Site Number 380105
  • Torino, Italy, 10126
    • Investigational Site Number 380104
• Latvia
  • Jelgava, Latvia, LV-3001
    • Investigational Site Number 428103
  • Ogre, Latvia, LV-5001
    • Investigational Site Number 428104
  • Riga, Latvia, LV-1002
    • Investigational Site Number 428102
  • Riga, Latvia, LV-1006
    • Investigational Site Number 428105
  • Sigulda, Latvia, LV-2150
    • Investigational Site Number 428101
• Lithuania
  • Jonava, Lithuania, LT-55201
    • Investigational Site Number 440104
  • Kaunas, Lithuania, LT-48259
    • Investigational Site Number 440103
  • Kaunas, Lithuania, LT-49456
    • Investigational Site Number 440102
  • Kaunas, Lithuania, LT-51270
    • Investigational Site Number 440101
  • Klaipeda, Lithuania, LT-92288
    • Investigational Site Number 440105
• Mexico
  • Chihuahua, Mexico, 31200
    • Investigational Site Number 484108
  • Cuernavaca, Mexico, 62250
    • Investigational Site Number 484101
  • Durango, Mexico, 34080
    • Investigational Site Number 484111
  • Guadalajara, Mexico, 44150
    • Investigational Site Number 484104
  • Guadalajara, Mexico, 44210
    • Investigational Site Number 484109
  • Guadalajara, Mexico, 44600
    • Investigational Site Number 484107
  • Guadalajara, Mexico, 44650
    • Investigational Site Number 484105
  • Guadalajara, Mexico, 44656
    • Investigational Site Number 484110
  • Mexico Df, Mexico, 11850
    • Investigational Site Number 484103
  • Monterrey, Mexico, 64000
    • Investigational Site Number 484106
  • México, Mexico, 06700
    • Investigational Site Number 484102
• Poland
  • Bialystok, Poland, 15-435
    • Investigational Site Number 616101
  • Bydgoszcz, Poland, 85-822
    • Investigational Site Number 616103
  • Bytom, Poland, 41-902
    • Investigational Site Number 616102
  • Krakow, Poland, 31-455
    • Investigational Site Number 616106
  • Krakow, Poland, 31-548
    • Investigational Site Number 616104
  • Pulawy, Poland, 24-100
    • Investigational Site Number 616105
  • Warszawa, Poland, 02-507
    • Investigational Site Number 616107
• Romania
  • Bacau, Romania, 600114
    • Investigational Site Number 642105
  • Cluj Napoca, Romania, 400006
    • Investigational Site Number 642108
  • Deva, Romania, 330084
    • Investigational Site Number 642106
  • Galati, Romania, 800098
    • Investigational Site Number 642113
  • Hunedoara, Romania, 331057
    • Investigational Site Number 642107
  • Iasi, Romania, 700547
    • Investigational Site Number 642117
  • Oradea, Romania, 410169
    • Investigational Site Number 642103
  • Oradea, Romania, 410169
    • Investigational Site Number 642104
  • Pitesti, Romania, 110084
    • Investigational Site Number 642112
  • Ploiesti, Romania, 100342
    • Investigational Site Number 642114
  • Resita, Romania, 320076
    • Investigational Site Number 642102
  • Sibiu, Romania, 550371
    • Investigational Site Number 642111
  • Targu Mures, Romania, 540142
    • Investigational Site Number 642109
  • Targu Mures, Romania, 540142
    • Investigational Site Number 642110
  • Timisoara, Romania, 300133
    • Investigational Site Number 642116
  • Timisoara, Romania, 300456
    • Investigational Site Number 642101
  • Timisoara, Romania, 300723
    • Investigational Site Number 642115
• Russian Federation
  • Moscow, Russian Federation, 117036
    • Investigational Site Number 643111
  • Moscow, Russian Federation, 119991
    • Investigational Site Number 643107
  • Moscow, Russian Federation, 129110
    • Investigational Site Number 643105
  • Penza, Russian Federation, 440026
    • Investigational Site Number 643110
  • Saratov, Russian Federation, 410030
    • Investigational Site Number 643102
  • St-Petersburg, Russian Federation, 194044
    • Investigational Site Number 643101
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643104
  • St-Petersburg, Russian Federation, 194354
    • Investigational Site Number 643109
  • St-Petersburg, Russian Federation, 195112
    • Investigational Site Number 643108
  • St-Petersburg, Russian Federation, 195257
    • Investigational Site Number 643103
  • St. Petersburg, Russian Federation, 194358
    • Investigational Site Number 643106
• Spain
  • El Ferrol, Spain, 15403
    • Investigational Site Number 724102
  • La Coruña, Spain, 15006
    • Investigational Site Number 724105
  • Malaga, Spain, 29010
    • Investigational Site Number 724103
  • Sevilla, Spain, 41010
    • Investigational Site Number 724104
• Ukraine
  • Chernivtsi, Ukraine, 58022
    • Investigational Site Number 804104
  • Donetsk, Ukraine, 83003
    • Investigational Site Number 804107
  • Donetsk, Ukraine, 83059
    • Investigational Site Number 804103
  • Mykolaiv, Ukraine, 54003
    • Investigational Site Number 804108
  • Odessa, Ukraine, 65059
    • Investigational Site Number 804110
  • Vinnytsya, Ukraine, 21001
    • Investigational Site Number 804105
  • Vinnytsya, Ukraine, 21010
    • Investigational Site Number 804102
  • Zaporizhia, Ukraine, 69600
    • Investigational Site Number 804111
• United Kingdom
  • Ashton-Under-Lyne, United Kingdom, OL6 9RW
    • Investigational Site Number 826006
  • Birmingham, United Kingdom, B9 5SS
    • Investigational Site Number 826002
  • Carmarthen, United Kingdom, SA31 2AF
    • Investigational Site Number 826007
  • Chester, United Kingdom, CH2 1UL
    • Investigational Site Number 826005
  • Coventry, United Kingdom, CV1 4FH
    • Investigational Site Number 826008
  • Dundee, United Kingdom, DD1 9SI
    • Investigational Site Number 826009
  • Durham, United Kingdom, DH1 5TW
    • Investigational Site Number 826001
  • Haddington, United Kingdom, EH41 3PF
    • Investigational Site Number 826011
  • Leicester, United Kingdom, LE5 4PW
    • Investigational Site Number 826012
  • Plymouth, United Kingdom, PL6 8BX
    • Investigational Site Number 826010
  • Sheffield, United Kingdom, S5 7AU
    • Investigational Site Number 826004
  • St Helens, United Kingdom, WA93DA
    • Investigational Site Number 826003
• United States
  • Arizona
    • Sun City, Arizona, United States, 85351
      • Investigational Site Number 840043
    • Tempe, Arizona, United States, 85282
      • Investigational Site Number 840042
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Investigational Site Number 840003
  • California
    • La Mesa, California, United States, 91942
      • Investigational Site Number 840031
    • Mission Viejo, California, United States, 92691
      • Investigational Site Number 840005
    • Northridge, California, United States, 91325
      • Investigational Site Number 840057
    • Santa Ana, California, United States, 92704
      • Investigational Site Number 840035
    • Temecula, California, United States, 92591
      • Investigational Site Number 840002
    • Walnut Creek, California, United States, 94598
      • Investigational Site Number 840037
    • West Hills, California, United States, 91345
      • Investigational Site Number 840023
  • Colorado
    • Denver, Colorado, United States, 80246
      • Investigational Site Number 840041
  • Florida
    • Miami, Florida, United States, 33136
      • Investigational Site Number 840012
    • Miami, Florida, United States, 33142
      • Investigational Site Number 840061
  • Georgia
    • Lawrenceville, Georgia, United States, 30045
      • Investigational Site Number 840045
  • Idaho
    • Nampa, Idaho, United States, 83686
      • Investigational Site Number 840036
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Investigational Site Number 840024
    • Evanston, Illinois, United States, 60201
      • Investigational Site Number 840009
  • Indiana
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840004
    • Avon, Indiana, United States, 46123
      • Investigational Site Number 840055
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Investigational Site Number 840027
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Investigational Site Number 840006
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Investigational Site Number 840047
    • Paducah, Kentucky, United States, 42003
      • Investigational Site Number 840056
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Investigational Site Number 840022
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Investigational Site Number 840016
    • Rockville, Maryland, United States, 20852
      • Investigational Site Number 840017
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Investigational Site Number 840025
    • Dearborn, Michigan, United States, 48124
      • Investigational Site Number 840048
    • Kalamazoo, Michigan, United States, 49048
      • Investigational Site Number 840026
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Investigational Site Number 840049
  • New York
    • New Hyde Park, New York, United States, 11042
      • Investigational Site Number 840029
    • Smithtown, New York, United States, 11787
      • Investigational Site Number 840060
    • Staten Island, New York, United States, 10301-3914
      • Investigational Site Number 840030
  • North Carolina
    • Salisbury, North Carolina, United States, 28144
      • Investigational Site Number 840011
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Investigational Site Number 840028
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Investigational Site Number 840007
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Investigational Site Number 840021
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Investigational Site Number 840052
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Investigational Site Number 840032
    • Nashville, Tennessee, United States, 37232
      • Investigational Site Number 840033
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Investigational Site Number 840034
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 840001
    • Houston, Texas, United States, 77081
      • Investigational Site Number 840020
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Investigational Site Number 840018
    • Salem, Virginia, United States, 24153
      • Investigational Site Number 840015
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53217
      • Investigational Site Number 840010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Participants with type 2 diabetes mellitus diagnosed at least 1 year before screening visit (V1).
• Participants treated with basal insulin for at least 6 months.
• Participants treated for at least 3 months prior to visit 1 with a stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection). The insulin dose should be stable (± 20%) and ≥20 U/day for at least 2 months prior to visit 1.
• Participants treated with basal insulin alone or in combination with 1 to 3 oral anti-diabetic drugs (OADs) that could be: metformin (≥1.5 g/day or maximal tolerated dose), a sulfonylurea (SU), a dipeptidyl-peptidase-4 (DPP-4) inhibitor, a glinide. The dose of OADs should be stable for at least 3 months prior to visit 1.

Exclusion criteria:

• At screening: age < legal age of majority.
• At screening, HbA1c: <7.5% and >10.0% for participants treated with basal insulin alone or in combination with metformin only; < 7.0% and > 10.0% for participants treated with basal insulin and a combination of oral anti-diabetic drugs which included a SU and/or a DPP-4 inhibitor and/or a glinide.
• Women of childbearing potential with no effective contraceptive method, pregnancy or lactation.
• Type 1 diabetes mellitus.
• Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria within 3 months prior to screening.
• Previous treatment with short or rapid acting insulin other than in relation to hospitalization or an acute illness.
• Any previous treatment with lixisenatide, or any discontinuation from another glucagon-like peptide 1 (GLP-1) receptor agonist due to safety/tolerability issue or lack of efficacy.
• At screening, Body Mass Index (BMI) ≤20 or >40 kg/m^2.
• Weight change of more than 5 kg during the 3 months prior to the screening visit; use of weight loss drugs within 3 months prior to screening.
• Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures.
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.
• At screening resting systolic blood pressure >180 mmHg or diastolic blood pressure >95 mmHg.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposed to MTC (e.g. multiple endocrine neoplasia syndromes).
• Contraindication related to metformin (for participant receiving this treatment), insulin glargine, insulin glulisine or lixisenatide.
• Participants with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease.
• At screening, amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN).
• At screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 ULN.
• At screening calcitonin ≥20 pg/ml (5.9 pmol/L).

Exclusion Criteria for randomization at the end of the screening period before randomization:

• HbA1c <7.0% or >9.0%.
• 7-day mean fasting SMPG >140 mg/dl (7.8 mmol/L).
• Amylase and/or lipase >3 times ULN.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lixisenatide; Lixisenatide 10 mcg once daily (QD) for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to Week 26 on top of insulin glargine with or without metformin.	Drug: Lixisenatide (AVE0010); Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection 30 to 60 minutes before breakfast or dinner.; Other Names: Lyxumia®; Device: Disposable self-injector prefilled pen (Delta 14®); Drug: Insulin Glargine (Mandatory background drug); Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL).; Other Names: Device: Disposable self-injector prefilled pen (Lantus® Solostar®); Drug: Metformin (Background drug); Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study.
Active Comparator: Insulin Glulisine QD; Insulin glulisine QD from randomization up to Week 26 on top of Insulin glargine with or without metformin.	Drug: Insulin Glargine (Mandatory background drug); Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL).; Other Names: Device: Disposable self-injector prefilled pen (Lantus® Solostar®); Drug: Metformin (Background drug); Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study.; Drug: Insulin glulisine QD; Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before breakfast or dinner. The initial dose was 3-5 units and then individually titrated to obtain the SMPG value >5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before lunch (if administered at breakfast) or at bedtime (if administered at dinner).; Other Names: HMR1964; Device: Disposable self-injector prefilled pen (Apidra® Solostar®)
Active Comparator: Insulin Glulisine TID; Insulin glulisine thrice daily (TID) from randomization up to Week 26 on top of Insulin glargine with or without metformin.	Drug: Insulin Glargine (Mandatory background drug); Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL).; Other Names: Device: Disposable self-injector prefilled pen (Lantus® Solostar®); Drug: Metformin (Background drug); Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study.; Drug: Insulin glulisine TID; Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before each meal. The initial dose was 3-5 units for each meal and then individually titrated to obtain the SMPG value >5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before the next meal or at bedtime (for injection at dinner).; Other Names: HMR1964; Device: Disposable self-injector prefilled pen (Apidra® Solostar®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c From Baseline to Week 26	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.	Baseline, Week 26
Change in Body Weight From Baseline to Week 26	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.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HbA1c Level <7% and ≤6.5% at Week 26	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.	Week 26
Percentage of Participants With no Weight Gain at Week 26	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.	Week 26
Change in Average 7-point SMPG Profiles From Baseline to Week 26	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.	Baseline, Week 26
Change in FPG From Baseline to Week 26	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.	Baseline, Week 26
Change in PPG From Baseline to Week 26 (in Participants Who Had an Injection of Investigational Medicinal Product [IMP] Before Breakfast)	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.	Baseline, Week 26
Change in Glucose Excursions From Baseline to Week 26 (in Participants Who Had an Injection of IMP Before Breakfast)	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.	Baseline, Week 26
Change in Insulin Glargine Dose From Baseline to Week 26	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.	Baseline, Week 26
Insulin Glulisine Dose at Week 26	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.	Week 26
Total Insulin Dose at Week 26	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.	Week 26
Percentage of Participants With Documented Symptomatic and Severe Symptomatic Hypoglycemia	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.	First dose of study drug up to 3 days after the last dose administration (maximum of 185 days)
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	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.	Week 26
Percentage of Participants Who Reached the Target of HbA1c <7% and Had no Weight Gain at Week 26	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.	Week 26
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	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.	Week 26

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Rosenstock J, Handelsman Y, Vidal J, Ampudia Blasco FJ, Giorgino F, Liu M, Perfetti R, Meier JJ. Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes. Diabetes Obes Metab. 2018 Dec;20(12):2821-2829. doi: 10.1111/dom.13462. Epub 2018 Aug 13.
• Tabak AG, Anderson J, Aschner P, Liu M, Saremi A, Stella P, Tinahones FJ, Wysham C, Meier JJ. Efficacy and Safety of iGlarLixi, Fixed-Ratio Combination of Insulin Glargine and Lixisenatide, Compared with Basal-Bolus Regimen in Patients with Type 2 Diabetes: Propensity Score Matched Analysis. Diabetes Ther. 2020 Jan;11(1):305-318. doi: 10.1007/s13300-019-00735-7. Epub 2019 Dec 17.
• Rosenstock J, Guerci B, Hanefeld M, Gentile S, Aronson R, Tinahones FJ, Roy-Duval C, Souhami E, Wardecki M, Ye J, Perfetti R, Heller S; GetGoal Duo-2 Trial Investigators. Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial. Diabetes Care. 2016 Aug;39(8):1318-28. doi: 10.2337/dc16-0014. Epub 2016 May 23.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: January 11, 2013
• First Submitted That Met QC Criteria: January 11, 2013
• First Posted (Estimate): January 15, 2013

Study Record Updates

• Last Update Posted (Estimate): January 4, 2017
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Insulin glulisine; Lixisenatide
• Other Study ID Numbers: EFC12626; 2012-004096-38 (EudraCT Number); U1111-1131-4936 (Other Identifier: UTN)