Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure

Condition(s) targeted: Diabetes Mellitus, Type 2

Intervention: Insulin glargine (Drug); Liraglutide (Drug); Metformin (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Sanofi

Official(s) and/or principal investigator(s):
Clinical Sciences & Operations, Study Director, Affiliation: Sanofi

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

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period

Secondary outcome:

Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period

Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period

Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period

Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period

Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period

Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period

Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period

Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period

Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period

Body Weight: Change From Baseline to the End of the Comparative Period

Body Weight: Change From Beginning to End of the Extension Period

Daily Dose of Insulin Glargine

Daily Dose of Liraglutide

Daily Dose of Insulin Glargine Administered During the Extension Period

Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period

Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period

Detailed description: 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

Minimum age: 35 Years. Maximum age: 75 Years. Gender(s): Both.

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.

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Starting date: July 2010
Last updated: March 5, 2014