Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Insulin glargine; Liraglutide; Metformin
Intervention description: 100 Units/mL solution for injection in a pre-filled SoloStar pen; 6 mg/mL solution for injection in a 3-mL pre-filled pen (18mg); Metformin was a background treatment, mandatory for each patient randomized in the study (at the minimum dose of 1g/day). It was not supplied by the sponsor.
Intervention MeSH terms: Metformin; Insulin Glargine; Liraglutide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 978.0
Sex: All
Minimum age: 35 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      Primary objective:

      To demonstrate the superiority of insulin glargine over liraglutide in terms of percentage of
      patients reaching a Glycosylated Haemoglobin (HbA1c) < 7% at the end of the comparative
      period (24 weeks) in Type 2 diabetic patients failing lifestyle management and oral agents

      Secondary objectives of the comparative period (24 weeks):

      >To assess the effect of insulin glargine in comparison with liraglutide on:

        -  HbA1c level

        -  Percentage of patients whose HbA1c has decreased but remains >= 7% at the end of the
           comparative period

        -  Percentage of patients whose HbA1c has increased at the end of the comparative period

        -  Fasting Plasma Glucose (FPG)

        -  7-point Plasma Glucose (PG) profiles

        -  Hypoglycemia occurrence

        -  Body weight

        -  Adverse events

      Objectives of the extension period (24 weeks):

      >To assess the effect of insulin glargine in patients not adequately controlled with
      liraglutide on:

        -  HbA1c level

        -  FPG

        -  7-point PG profiles

        -  Hypoglycemia occurrence

        -  Body weight

        -  Adverse events
    

Eligibility criteria:

        Inclusion criteria (comparative period):

          -  Patients With Type 2 Diabetes diagnosed for at least 1 year,

          -  Treated with lifestyle interventions and metformin at the maximum tolerated dosage
             (with a minimum daily dosage of 1g), either alone or in combination with an oral
             insulin secretagogue (sulfonylurea, glinide or DiPeptidyl Peptidase IV inhibitor), for
             more than 3 months,

          -  7.5% < HbA1c <= 12%,

          -  Body Mass Index (BMI) between 25 and 40 kg/m2 inclusively,

          -  Ability and willingness to perform PG (Plasma Glucose) self monitoring using the
             sponsor-provided glucose meter and to complete the patient diary,

          -  Willingness and ability to comply with the study protocol,

          -  Signed informed consent obtained prior to any study procedure.

        Inclusion criteria (extension period):

          -  Patients treated with liraglutide (at the maximal tolerated dosage), having a mean FPG
             ≥ 250 mg/dL at visit 10 (Week 12) or visit 11 (Week 18), or a HbA1c≥ 7% at visit 12
             (Week 24)

          -  Dosage of metformin compliant with the inclusion criteria of visit 1 (i.e. maximum
             tolerated dosage, with a minimum daily dosage of 1g), and maintained stable during the
             comparative period.

        Exclusion criteria:

          -  Previous treatment with Glucagon Like Peptide-1 analogues or insulin in the past year
             (except in case of temporary treatment for gestational diabetes, surgery,
             hospitalization...),

          -  Treatment with thiazolidinediones or α-Glucosidases inhibitors within 3 months prior
             to study entry,

          -  Diabetes other than Type 2 diabetes (e.g. secondary to pancreatic disorders, drug or
             chemical agents intake),

          -  Pregnant women (women of childbearing potential must have a negative pregnancy test at
             study entry and a medically approved contraceptive method),

          -  Lactating women,

          -  Hospitalized patients (except hospitalization for routine diabetes check-up),

          -  Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy
             occurrence in the 6 months prior to study entry, or any other unstable (rapidly
             progressing) retinopathy that may require photocoagulation or surgical treatment
             during the study, documented by a retina examination within 2 years prior to study
             entry,

          -  Impaired renal function (creatinine clearance < 60 mL/mn),

          -  Impaired hepatic function (Alanine Aminotransferase, Aspartate Aminotransferase 2.5
             times the upper limit of normal range),

          -  Personal or family history of medullary thyroid carcinoma,

          -  Multiple endocrine neoplasia syndrome type 2,

          -  Severe gastro-intestinal disease (including inflammatory bowel disease or diabetic
             gastroparesis),

          -  Congestive heart failure,

          -  History of acute pancreatitis,

          -  Treatment with corticosteroids with potential systemic action for more than 10 days
             within 3 months prior to study entry,

          -  Alcohol or drug abuse in the past 5 years,

          -  History of sensitivity to the study drugs or to drugs with a similar chemical
             structure.

          -  Night shift worker,

          -  Presence of any condition (medical, psychological, social or geographical), current or
             anticipated that would compromise the patients safety or limit the patient successful
             participation in the study,

          -  Participation in a clinical trial (drug or device) within 3 months prior to study
             entry,

          -  Refusal or inability to give informed consent to participate in the study,

          -  Patient is the Investigator or any sub-Investigator, research assistant, pharmacist,
             study coordinator, other staff or relative thereof directly involved in the conduct of
             the protocol.

        Additional exclusion criteria for the extension period:

          -  Treatment with oral antidiabetic drugs other than metformin and patient's usual
             sulfonylurea if any, or with insulin during the comparative period (except in case of
             an emergency, for a period of time less than 7 days),

          -  Treatment with corticosteroids with potential systemic action within the last 3 months
             of the comparative period.

          -  History of sensitivity to insulin glargine.