Phase 3
Completed N=514
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
Source: ClinicalTrials.gov NCT02787551 ↗Enrolled (actual)
514
Serious AEs
5.6%
Results posted
Jun 2019
Primary outcomePrimary: Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 26: Core Period — -1.02; -0.38 percentage of HbA1c — p=<0.0001
◆ Published Evidence
Established
80citations · ~11 / year
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.
Summary
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.
Linked Publications (5)
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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.
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Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM).
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Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.
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Concomitant iGlarLixi and Sodium-Glucose Co-transporter-2 Inhibitor Therapy in Adults with Type 2 Diabetes: LixiLan-G Trial and Real-World Evidence Results.
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Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 26: Core Period |
-1.02; -0.38 | <0.0001 sig |
| PRIMARY Change From Baseline in Glycated Hemoglobin (HbA1c) to Week 52: Single Arm Extension Period |
-1.01 | — |
| SECONDARY Percentage of Participants Reaching HbA1c <7% or <=6.5% at Week 26: Core Period |
61.9; 25.7; 40.5; 9.9 | <.0001 sig |
| SECONDARY Percentage of Participants Reaching HbA1c <7 % or <=6.5% at Week 52: Single Arm Extension Period |
64.1; 42.7 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) to Week 26: Core Period |
-2.28; -0.60 | <0.0001 sig |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52: Single Arm Extension Period |
-2.27 | — |
| SECONDARY Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 26: Core Period |
-1.69; -0.67 | <0.0001 sig |
| SECONDARY Change From Baseline in the Daily Average of the 7-point Self-monitored Plasma Glucose (SMPG) to Week 52: Single Arm Extension Period |
-1.68 | — |
| SECONDARY Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 26: Core Period |
-3.96; -1.11 | <0.0001 sig |
| SECONDARY Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) During Standardized Meal Test to Week 52: Single Arm Extension Period |
-4.30 | — |
| SECONDARY Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 26: Core Period |
-1.51; -0.52 | <0.0001 sig |
| SECONDARY Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test to Week 52: Single Arm Extension Period |
-1.85 | — |
| SECONDARY Percentage of Participants Requiring Rescue Therapy During the 26 Week Treatment Period: Core Period |
4.8; 15.0 | — |
| SECONDARY Percentage of Participants Requiring Rescue Therapy During the 52 Week Treatment Period: Single Arm Extension Period |
1.5 | — |
| SECONDARY Change From Baseline in Body Weight at Week 26: Core Period |
1.89; -1.14 | — |
| SECONDARY Change From Baseline in Body Weight to Week 52: Single Arm Extension Period |
2.78 | — |
| SECONDARY Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Core Period |
1.54; 0.08; 0.25; 0.01 | — |
| SECONDARY Number of Documented Symptomatic Hypoglycemia Events Per Participant-Year: Single Arm Extension Period |
1.59; 0.24 | — |
Eligibility Criteria
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 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 [ 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 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.
Data sourced from ClinicalTrials.gov (NCT02787551) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.