Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure

A 24-week, Multicenter, International, Randomized (1:1), Parallel-group, Open-label, Comparative Study of Insulin Glargine Versus Liraglutide in Insulin-naïve Patients With Type 2 Diabetes Treated With Oral Agents and Not Adequately Controlled, Followed by a 24-week Extension Period With Insulin Glargine for Patients Not Adequately Controlled With Liraglutide

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

Maximum estimated study duration per patient: either 27 weeks (patients randomized to insulin glargine arm) or 51 weeks (patients randomized to liraglutide arm) broken down as follow:

• A 2-week of screening period,
• A 24-week comparative period,
• A 24-week extension period (only for patients treated with liraglutide, not adequately controlled at the end of the comparative period),
• A 1-week follow-up period

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.