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
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Insulin glargine/lixisenatide fixed ratio combination; liraglutide; exenatide; exenatide extended-release; albiglutide; dulaglutide; Background therapy: Oral Anti-diabetic Drug (Metformin, Pioglitazone, SGLT2 inhibitor)
Intervention description: Pharmaceutical form: solution for injection
Route of administration: subcutaneous; Pharmaceutical form: solution for injection
Route of administration: subcutaneous; Pharmaceutical form: solution for injection
Route of administration: subcutaneous; Pharmaceutical form: solution for injection
Route of administration: subcutaneous; Pharmaceutical form: solution for injection
Route of administration: subcutaneous; Pharmaceutical form: solution for injection
Route of administration: subcutaneous; Pharmaceutical form: tablet Route of administration: oral If previously taken, doses to remain stable through the study.
Intervention MeSH terms: Metformin; Insulin Glargine; Pioglitazone; Liraglutide; Exenatide; Dulaglutide; Lixisenatide; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; rGLP-1 protein
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 514.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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 <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.