efficacy assessment of insulin glargine versus liraglutide after oral agents failure

Conditions: Diabetes Mellitus, Type 2

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

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

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.