Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Liraglutide; Insulin Glargine; Metformin
Intervention description: Pharmaceutical form: solution for injection self-administered with a pen-like injector (OptiClik®).
Route of administration: subcutaneous; Pharmaceutical form:solution for injection
Route of administration: subcutaneous; Doses to be adjusted to maintain a fasting self-measured plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL); If previously taken metformin to be continued at stable dose throughout the study
Intervention MeSH terms: Metformin; Insulin Glargine; Liraglutide; Lixisenatide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      - To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg once daily
      (QD) as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma
      glucose (PPG) assessed as area under the plasma glucose-concentration-time curve (AUC) after
      a standardized breakfast at the end of a 8-week treatment period in participants with type 2
      diabetes mellitus (T2DM) not adequately controlled with insulin glargine (± metformin).

      Secondary Objectives:

        -  To assess the effects of lixisenatide 20 μg QD as compared to liraglutide 1.2 QD or 1.8
           mg QD after an 8-week treatment period in participants with T2DM not adequately
           controlled with insulin glargine (± metformin) on:

             -  Post-prandial C-peptide, glucagon and appetite perceptions after a standardized
                breakfast,

             -  Appetite perceptions after standardized dinner,

             -  Gastric emptying after a standardized labelled test meal,

             -  Fasting plasma glucose, 24-hour plasma glucose profile,

             -  Glycosylated hemoglobin (HbA1c),

             -  Insulin glargine dose,

             -  7-point self monitored plasma glucose (SMPG),

             -  Body weight and waist circumference,

             -  24-hour heart rate and blood pressure,

        -  To assess lixisenatide and liraglutide safety and tolerability as add on treatment to
           insulin glargine (± metformin).
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with T2DM diagnosed at least 1 year before the screening visit.

          -  Treatment with neutral protamine hagedorn (NPH) or insulin glargine for at least 3
             months and at a stable dose (±20%) of at least 10 IU/day (for at least 2 months prior
             to screening) alone or combined with a stable dose of metformin with or without
             dipeptidyl peptidase 4 (DPP-4) inhibitor or sulfonylurea.

          -  Glycosylated hemoglobin (HbA1c) ≥6.5 and ≤9.5%.

          -  Body mass index (BMI) between 20 and 40 kg/m^2.

        Exclusion criteria:

          -  Pregnant women or breastfeeding women.

          -  Clinically relevant history of gastrointestinal disease associated with prolonged
             nausea and vomiting, including, but not limited to, gastroparesis and gastroesophageal
             reflux disease requiring medical treatment within 6 months prior to the time of
             screening.

          -  Any previous treatment with lixisenatide or participation in a previous study with
             lixisenatide (AVE0010), and any previous treatment with liraglutide stopped for safety
             concern or lack of efficacy.

          -  Allergic reaction to any glucagon-like peptide-1 (GLP-1) agonist in the past (eg,
             exenatide) or to metacresol.

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
             stomach/gastric surgery, inflammatory bowel disease.

          -  Personal or family history of medullary thyroid cancer (MTC) or a genetic condition
             that predisposes to MTC.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.