Efficacy and Safety of Lixisenatide Versus Insulin Glulisine on Top of Insulin Glargine With or Without Metformin in Type 2 Diabetic Patients (GetGoal Duo-2)

• Change from baseline in HbA1c [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Change from baseline in body weight [ Time Frame: week 26 ] [ Designated as safety issue: No ]

• Percentage of patients reaching HbA1c <7% [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Percentage of patients reaching HbA1c ≤6.5% [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Change in body weight from baseline [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Percentage of patients with no weight gain [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Change in 7-point SMPG profiles from baseline [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Change from baseline in FPG [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Change from baseline in post-prandial glucose /glucose excursions during a standardized meal test (subset of patients) [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Change from baseline in insulin glargine dose [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Daily dose of insulin glulisine [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Total daily dose of insulin [ Time Frame: week 26 ] [ Designated as safety issue: No ]
• Documented (PG <60 mg/dl) symptomatic hypoglycemia (percentage of subjects with at least one episode, number of events per patient-year) [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
• Severe hypoglycemia [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]

Primary Objective:

- To compare lixisenatide versus insulin glulisine in terms of HbA1c reduction and body weight change at week 26 in type 2 diabetic patients not adequately controlled on insulin glargine ± metformin.

Secondary Objectives:

- To compare the treatments/regimens on:

• The percentage of patients reaching the target of HbA1c <7% or ≤6.5%
• Body weight
• Self-Monitored Glucose profiles
• Fasting Plasma Glucose (FPG)
• Post-prandial plasma glucose /glucose excursions during a standardized meal test (subset of patients)
• Daily doses of insulins
• Safety and tolerability

Approximately 41 weeks including a 26 week treatment period

• Drug: lixisenatide (AVE0010)

  Pharmaceutical form:solution for injection (disposable self injector)

  Route of administration: subcutaneous injection

• Drug: insulin glulisine (HMR1964)

  Pharmaceutical form:solution for injection (disposable self injector)

  Route of administration: subcutaneous injection

  Other Name: Apidra©

• Experimental: lixisenatide
  lixisenatide once a day (injected before breakfast or dinner) on top of insulin glargine with or without metformin. Starting dose will be 10µg, then increased to the 20µg maintenance dose after 2 weeks
  Intervention: Drug: lixisenatide (AVE0010)
• Active Comparator: insulin glulisine once a day
  Insulin glulisine once a day (injected before breakfast or dinner) on top of insulin glargine with or without metformin. Treatment will be initiated and then individually titrated
  Intervention: Drug: insulin glulisine (HMR1964)
• Active Comparator: insulin glulisine three times a day
  Insulin glulisine three times a day (injected before breakfast, lunch and dinner) on top of insulin glargine with or without metformin. Treatment will be initiated and then individually titrated
  Intervention: Drug: insulin glulisine (HMR1964)

Inclusion criteria :

• Patients with type 2 diabetes mellitus diagnosed at least 1 year before screening visit (V1).
• Patients treated with basal insulin for at least 6 months.
• Patients treated for at least 3 months prior to visit 1 with a stable basal insulin regimen (ie type of insulin and time/frequency of the injection). The insulin dose should be stable (± 20 %) and ≥20 U/day for at least 2 months prior to visit 1.
• Patients treated with basal insulin alone or in combination with 1 to 3 oral anti-diabetic drugs (OADs) that can be: metformin (≥1.5g/day or maximal tolerated dose), a sulfonylurea (SU), a dipeptidyl-peptidase-4 (DPP-4) inhibitor. The dose of OADs should be stable for at least 3 months prior to visit 1.

Exclusion criteria:

• At screening: age < legal age of majority
• At screening, HbA1c: < 7.5% and > 10.0% for patients treated with basal insulin alone or in combination with metformin only; < 7.0% and > 10.0% for patients treated with basal insulin and a combination of oral anti-diabetic drugs which includes a SU and/or a DPP-4 inhibitor
• Women of childbearing potential with no effective contraceptive method, pregnancy or lactation
• Type 1 diabetes mellitus
• Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria within 3 months prior to screening.
• Previous treatment with short or rapid acting insulin other than in relation to hospitalization or an acute illness.
• Previous treatment with exenatide, liraglutide or any other GLP-1 receptor agonist
• At screening, Body Mass Index (BMI) ≤20 or >40 kg/m².
• Weight change of more than 5 kg during the 3 months prior to the screening visit; use of weight loss drugs within 3 months prior to screening.
• Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures.
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.
• At screening resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 95 mmHg
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes)
• Contraindication related to metformin (for patient receiving this treatment), insulin glargine, insulin glulisine or lixisenatide.
• Patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease, if no treatment with metformin
• At screening, amylase and/or lipase > 3 times the upper limit of the normal laboratory range (ULN)
• At screening ALT or AST>3ULN
• At screening calcitonin ≥20 pg/ml (5.9 pmol/L)

Exclusion Criteria for randomization at the end of the screening period before randomization:

• HbA1c <7.0% or >9.0%.
• 7-day mean fasting SMPG >140 mg/dl (7.8 mmol/L).
• Amylase and/or lipase > 3 times ULN.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.