Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Combination Versus Insulin Glargine Alone on Top of Metformin in Type 2 Diabetic Patients
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Insulin glargine /lixisenatide Fixed Ratio Combination; Insulin glargine; Metformin (Background drug)
Intervention description: FRC was self-administered by subcutaneous (SC) injection within 1 hour before breakfast using pen-type injector (Tactipen®): 100 U/ml insulin glargine and 50 mcg Lixisenatide (ratio of 2 U/1 mcg). The initial dose was 10 U/5 mcg and then dose was adjusted weekly to reach and maintain fasting self-monitored plasma glucose (SMPG) of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L.; Insulin glargine (100 U/ml) was self-administered by SC injection before breakfast using pen-type injector (Lantus® Solostar®). The initial daily dose of insulin glargine was 10 U and then dose was adjusted weekly to reach and maintain fasting SMPG of 80 mg/dL to 100 mg/dL (4.4 mmol/L to 5.6 mmol/L).; Pharmaceutical form: Tablet; Route of administration: oral administration. To be kept at stable dose (≥1.5 g/day) throughout the study.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Lixisenatide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 323.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

        -  The purpose of this study was to compare insulin glargine/ lixisenatide fixed ratio
           combination (FRC) versus insulin glargine on glycemic control over 24 weeks, as
           evaluated by glycosylated hemoglobin (HbA1c) reduction in type 2 diabetic participants
           treated with metformin.

      Secondary Objectives:

        -  To compare insulin glargine/lixisenatide FRC versus insulin glargine over 24 weeks on:

             -  Glycemic control in relation to a meal as evaluated by post-prandial plasma glucose
                and glucose excursions during a standardized meal test;

             -  Percentage of participants reaching HbA1c <7% or ≤6.5%;

             -  7-point Self-Monitored Plasma Glucose (SMPG) profile;

             -  Body weight;

             -  Insulin glargine dose

             -  Fasting Plasma Glucose (FPG);

             -  Percentage of participants requiring rescue therapy during the 24-week open label
                treatment period;

        -  To assess safety and tolerability of insulin glargine/lixisenatide FRC.
    

Eligibility criteria:

        Inclusion criteria:

          -  Participants with type 2 diabetes mellitus diagnosed for at least 1 year.

          -  Metformin treatment at a stable dose of at least 1.5 g/day for at least 3 months prior
             to screening.

        Exclusion criteria:

          -  Age < legal age of adulthood (18 years).

          -  Screening HbA1c <7% or >10%.

          -  Screening FPG >250 mg/dL (>13.9 mmol/L).

          -  Pregnancy or lactation, women of childbearing potential with no effective
             contraceptive method.

          -  Type 1 diabetes mellitus.

          -  Treatment with glucose-lowering agent(s) other than metformin in a period of 3 months
             prior to screening.

          -  Use of insulin within the last 6 months.

          -  Previous use of insulin, except for episode(s) of short-term treatment (≤15
             consecutive days) due to intercurrent illness.

          -  Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN) at
             screening.

          -  Calcitonin ≥20 pg/ml (5.9 pmol/l) at screening.

          -  Alanine Transferase (ALT) >3 ULN at screening.

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy.

          -  Personal or immediate family history of medullary thyroid cancer (MTC) or genetic
             conditions that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes).

          -  Uncontrolled or inadequately controlled hypertension at the time of screening with a
             resting supine systolic or diastolic blood pressure >180 mmHg or >110 mmHg,
             respectively.

          -  Within the last 6 months prior to screening: history of heart failure requiring
             hospitalization, myocardial infarction, or stroke. Planned coronary, carotid or
             peripheral artery revascularisation procedures.

          -  Body Mass Index (BMI) ≤20 or >40 kg/m^2.

          -  Any previous treatment with lixisenatide

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.