Skip to content

Trial · Interventional

CompletedPhase 3Results postedRegistry data

Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Versus GLP-1 Receptor Agonist in Patients With Type 2 Diabetes, With a FRC Extension Period

Short name LixiLan-G

NCTNCT02787551 (opens ClinicalTrials.gov in a new tab)Other idEFC13794Other id2014-004850-32Other idU1111-1168-4639Other id2014
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
514 participants (actual)
Sponsor
Sanofi · Industry
Design
Randomized · Open label (no masking)
Countries
9 countries

United States, Canada, Estonia, Germany, Israel, Italy, Romania, Slovakia, Spain

Start
6 Jul 2016
Primary completion
25 May 2018
Completion
17 Nov 2018
First posted
1 Jun 2016 (estimated)
Last update posted
25 Mar 2022
Conditions
Type 2 Diabetes Mellitus

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2016201720182019
  1. Ph 3

    LixiLan-G

    NCT02787551

    6 Jul 2016 to 17 Nov 2018

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Primary Objective: To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) versus GLP-1 receptor agonist (GLP-1 RA) in hemoglobin A1c (HbA1c) change. Secondary Objectives: To compare the overall efficacy and safety of the insulin glargine/lixisenatide FRC to GLP-1 RA on top of metformin (with or without pioglitazone, with or without sodium-glucose co-transporter 2 \[SGLT2\] inhibitor) in participants with type 2 diabetes. To evaluate safety, efficacy and other endpoints of FRC up to the end of the extension period.

Interventions

  • Insulin glargine/lixisenatide fixed ratio combinationDrug
  • liraglutideDrug
  • exenatideDrug
  • exenatide extended-releaseDrug
  • albiglutideDrug
  • dulaglutideDrug
  • Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)Drug

Arms2

  • Experimental

    Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)

    Core period: FRC injected subcutaneously once daily (QD) for 26 weeks on top of oral anti-diabetic drug (OAD) therapy. Dose individually adjusted. Single arm extension period: Participants who completed core treatment period and met eligibility criteria entered in extension treatment period and received same treatment (FRC injected subcutaneously QD on top of OAD therapy) for 26 weeks (up to Week 52). Dose individually adjusted.

  • Active comparator

    GLP-1 Receptor Agonist

    Core period: GLP-1 RA receptor agonist (liraglutide QD, exenatide twice daily \[BID\], exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 26: Core Period

    Time frame · Baseline, Week 26

    Registry description

    Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least squares (LS) mean and standard error (SE) were obtained from Mixed-effect model with repeated measures (MMRM) to account for missing data using all available post baseline data during the 26 week treatment period.

  2. Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 52: Single Arm Extension Period

    Time frame · Baseline, Week 52

    Registry description

    Change in HbA1c was calculated by subtracting baseline value from Week 52 value.

Secondary outcomes(16)

  1. Percentage of Participants Reaching HbA1c <7% or <=6.5% at Week 26: Core Period

    Time frame · Week 26

    Registry description

    Participants without any available HbA1c assessment at Week 26 were considered as non-responders.

  2. Percentage of Participants Reaching HbA1c <7 % or <=6.5% at Week 52: Single Arm Extension Period

    Time frame · Week 52

    Registry description

    Participants without any available HbA1c assessment at Week 52 were considered as non-responders.

  3. Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26: Core Period

    Time frame · Baseline, Week 26

    Registry description

    Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period.

  4. Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52: Single Arm Extension Period

    Time frame · Baseline, Week 52

    Registry description

    Change in FPG was calculated by subtracting baseline value from Week 52 value.

  5. Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 26: Core Period

    Time frame · Baseline, Week 26

    Registry description

    The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal. Adjusted LS means and SE were obtained from MMRM to account for missing data using all available post baseline data during the 26 week treatment period.

  6. Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 52: Single Arm Extension Period

    Time frame · Baseline, Week 52

    Registry description

    The 7-point SMPG profile was measured at the following 7 points: pre-prandial and 2 hours postprandial for breakfast, lunch, dinner and at bedtime. Two hours postprandial (breakfast, lunch and dinner) was defined as 2 hours after the start of the meal.

  7. Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 26: Core Period

    Time frame · Baseline, Week 26

    Registry description

    The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 26 value. Missing data was imputed using last observation carried forward (LOCF).

  8. Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 52: Single Arm Extension Period

    Time frame · Baseline, Week 52

    Registry description

    The 2-hour PPG test measured blood glucose 2 hours after eating a liquid standardized breakfast meal. Change in PPG was calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF.

  9. Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 26: Core Period

    Time frame · Baseline, Week 26

    Registry description

    2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before investigational medicinal product (IMP) administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 26 value. Missing data was imputed using LOCF.

  10. Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 52: Single Arm Extension Period

    Time frame · Baseline, Week 52

    Registry description

    2-hour plasma glucose excursion = 2-hour PPG value minus plasma glucose value obtained 30 minutes prior to the start of meal and before IMP administration if IMP was injected before breakfast. Change in plasma glucose excursions were calculated by subtracting baseline value from Week 52 value. Missing data was imputed using LOCF.

  11. Percentage of Participants Requiring Rescue Therapy During the 26 Week Treatment Period: Core Period

    Time frame · From Baseline to Week 26

    Registry description

    Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c \>8%.

  12. Percentage of Participants Requiring Rescue Therapy During the 52 Week Treatment Period: Single Arm Extension Period

    Time frame · From Week 26 to Week 52

    Registry description

    Routine HbA1c value was used to determine the requirement of rescue medication. Threshold values at Week 12 or later on Week 12: HbA1c \>8%.

  13. Change From Baseline in Body Weight at Week 26: Core Period

    Time frame · Baseline, Week 26

    Registry description

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

  14. Change From Baseline in Body Weight to Week 52: Single Arm Extension Period

    Time frame · Baseline, Week 52

    Registry description

    Change in body weight was calculated by subtracting baseline value from Week 52 value.

  15. Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Core Period

    Time frame · From Baseline to Week 26

    Registry description

    Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of \<3.0 mmol/L (54 mg/dL) were also analyzed.

  16. Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Single Arm Extension Period

    Time frame · From Baseline to Week 52

    Registry description

    Documented symptomatic hypoglycemia was an event during which symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=3.9 mmol/L (70 mg/dL). Hypoglycemic episodes with plasma glucose of \<3.0 mmol/L (54 mg/dL) were also analyzed.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 26

Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 26: Core Period

GroupValue (percentage of HbA1c)Spread
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.020.048
GLP-1 Receptor Agonist-0.380.048
Primary outcomeMean· Baseline, Week 52

Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 52: Single Arm Extension Period

GroupValue (percentage of HbA1c)Spread
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.010.063
Secondary and other outcome results(6)
Secondary outcomeNumber· Week 26

Percentage of Participants Reaching HbA1c <7% or <=6.5% at Week 26: Core Period

GroupValue (percentage of participants)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)61.9
GLP-1 Receptor Agonist25.7
Secondary outcomeNumber· Week 52

Percentage of Participants Reaching HbA1c <7 % or <=6.5% at Week 52: Single Arm Extension Period

GroupValue (percentage of participants)
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)64.1
Secondary outcomeLeast squares mean· Baseline, Week 26

Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26: Core Period

GroupValue (millimoles per litre (mmol/L))Spread
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-2.280.120
GLP-1 Receptor Agonist-0.600.119
Secondary outcomeMean· Baseline, Week 52

Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52: Single Arm Extension Period

GroupValue (mmol/L)Spread
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-2.270.173
Secondary outcomeLeast squares mean· Baseline, Week 26

Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 26: Core Period

GroupValue (mmol/L)Spread
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.690.114
GLP-1 Receptor Agonist-0.670.112
Secondary outcomeMean· Baseline, Week 52

Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 52: Single Arm Extension Period

GroupValue (mmol/L)Spread
Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC)-1.680.176

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Fixed Ratio CombinationFRC injected subcutaneously QD for 26 weeks on top of OAD therapy. Dose individually adjusted (median exposure: 183 days).0 / 25510 / 25569 / 255
GLP-1 Receptor AgonistGLP-1 RA receptor agonist (liraglutide QD, exenatide BID, exenatide extended-release QW, albiglutide QW, or dulaglutide QW) injected subcutaneously for 26 weeks on top of OAD therapy. GLP-1 RAs were administered as per local labeling at the same dose schedule as prior to randomization (median exposure: 183 days).0 / 2569 / 25648 / 256
Fixed Ratio Combination Whole Study PeriodParticipants who completed core treatment period and met eligibility criteria entered in extension treatment period and received same treatment (FRC injected subcutaneously QD on top of OAD therapy) for 26 weeks (up to Week 52). Dose individually adjusted (median exposure: 365 days).1 / 20621 / 20675 / 206

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies4

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2019

6 results

Switching to iGlarLixi Versus Continuing Daily or Weekly GLP-1 RA in Type 2 Diabetes Inadequately Controlled by GLP-1 RA and Oral Antihyperglycemic Therapy: The LixiLan-G Randomized Clinical Trial.

Blonde et al. 2019Diabetes carecited by 75

PMID 31530665DOI 10.2337/dc19-1357PUB-31530665

Full text at the publisher6 results
Publisher pageSee results (6)

More studies

3 studies on this page

PubMed tag: none · 2022

Concomitant iGlarLixi and Sodium-Glucose Co-transporter-2 Inhibitor Therapy in Adults with Type 2 Diabetes: LixiLan-G Trial and Real-World Evidence Results.

Guja et al. 2022Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 6

PMID 34894329PMC8776928DOI 10.1007/s13300-021-01180-1PUB-34894329

Free to read · publisher termsCC BY-NC
Read at source

Indexing hint: Randomized controlled trial · 2022

Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.

Ferrannini et al. 2022Diabetes, obesity & metabolismcited by 7

PMID 35257461PMC9314929DOI 10.1111/dom.14688PUB-35257461

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2021

Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study.

Blonde et al. 2021Diabetes carecited by 7

PMID 33468520PMC7896258DOI 10.2337/dc20-2023PUB-33468520

Rights unknown
Source link

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedKuruvilla DE, Mann JI, Tepper SJ, Starling AJ, Panza G, Johnson MAL. Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM). Sci Rep. 2022 Mar 24;12(1):5110. doi: 10.1038/s41598-022-09071-6. PMID 35332216

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria : * Participants with type 2 diabetes mellitus diagnosed at least 1 year prior to screening visit. * Participants who were treated with one of the following GLP-1 receptor agonists for at least 4 months prior to screening visit 1 (V1), and with stable dose for at least 3 months prior to screening visit (V1): * Liraglutide (Victoza®) 1.8 milligram (mg) QD or 1.2 mg QD, if the 1.8 mg QD dose was not well tolerated according to the Investigator's judgment or * Exenatide (Byetta®) 10 microgram (µg) BID or of 5 µg BID, if 10 µg BID dose was not well tolerated according to the Investigator's judgment in combination with metformin (daily dose greater than equal to \[\>=\] 1500 mg/day or maximum tolerated dose \[MTD\]), with or without pioglitazone, with or without SGLT2 inhibitor, all at stable dose for at least 3 months prior to screening. or Participants who were treated with stable dose of one of the following GLP-1 receptor agonists for at least 6 months prior to screening visit (V1): * Exenatide extended-release (Bydureon®) 2 mg once weekly (QW), if well tolerated according to Investigator's judgment, * Albiglutide (Tanzeum®) 50 mg QW or 30 mg QW, if 50 mg QW was not well tolerated according to Investigator's judgment, * Dulaglutide (Trulicity®) 1.5 mg QW or 0.75 mg QW, if 1.5 mg QW was not well tolerated according to Investigator's judgment in combination with metformin (daily dose ≥1500 mg/day or MTD), with or without pioglitazone, with or without SGLT2 inhibitor, all at stable dose for at least 3 months prior to screening; -Signed written informed consent. Exclusion criteria: * At screening visit, age \<18. * Screening HbA1c \<7% and \>9%. * Pregnancy or lactation, women of childbearing potential with no effective contraceptive method. * Any use of antidiabetic drugs within 3 months prior to the screening visit other than those described in the inclusion criteria. * Previous treatment with insulin in the year prior to screening visit (note: short-term treatment with insulin \[\<=10 days\] due to intercurrent illness including gestational diabetes was allowed at the discretion of the study physician). * Laboratory findings at the time of screening, including: * Fasting plasma glucose (FPG) \>250 mg/dL (13.9 millimoles per litre \[mmol/L\]), * Amylase and/or lipase \>3 times the upper limit of the normal laboratory range (ULN), * Alanine transaminase or aspartate transaminase \>3 ULN, * Calcitonin \>=20 pg/mL (5.9 pmol/L), * Positive pregnancy test. * Participant who had renal function impairment with estimated glomerular filtration rate \<30mL/min/1.73m\^2 (using the Modification of Diet in Renal Disease formula) or end-stage renal disease. * Contraindication to use of insulin glargine, or lixisenatide or GLP-1 receptor agonist (Victoza®, Byetta®, Bydureon®, Tanzeum® or Trulicity®) according to local labeling. * Any contraindication to metformin or pioglitazone or SGLT2 inhibitor use, according to local labeling. * History of hypersensitivity to insulin glargine, or to any of the excipients. * History of allergic reaction to any GLP-1 receptor agonist or to meta-cresol. * Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia type 2 syndromes). * History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy. * Body mass index \<=20 or \>40 kg/m\^2. Exclusion criteria for the extension period: * Participants in the FRC arm with a rescue therapy and HbA1c \>8% at week 22. * Participants in the FRC arm who discontinued prematurely from FRC treatment before week 26. * Participants in the GLP-1 RA treatment arm after randomization. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

PepBank is a research reference. Talk to a doctor before you use any peptide.