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

Primary Objective:

- To compare lixisenatide versus insulin glulisine in terms of glycosylated hemoglobin (HbA1c) reduction and body weight change at Week 26 in type 2 diabetic participants not adequately controlled on insulin glargine ± metformin.

Secondary Objectives:

- To compare the treatments/regimens on:

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

Approximately 41 weeks including a 26 week treatment period.

Eligibility Criteria:
Inclusion criteria :

* Participants with type 2 diabetes mellitus diagnosed at least 1 year before screening visit (V1).
* Participants treated with basal insulin for at least 6 months.
* Participants treated for at least 3 months prior to visit 1 with a stable basal insulin regimen (i.e. 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.
* Participants treated with basal insulin alone or in combination with 1 to 3 oral anti-diabetic drugs (OADs) that could be: metformin (≥1.5 g/day or maximal tolerated dose), a sulfonylurea (SU), a dipeptidyl-peptidase-4 (DPP-4) inhibitor, a glinide. 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 participants treated with basal insulin alone or in combination with metformin only; \< 7.0% and \> 10.0% for participants treated with basal insulin and a combination of oral anti-diabetic drugs which included a SU and/or a DPP-4 inhibitor and/or a glinide.
* 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.
* Any previous treatment with lixisenatide, or any discontinuation from another glucagon-like peptide 1 (GLP-1) receptor agonist due to safety/tolerability issue or lack of efficacy.
* At screening, Body Mass Index (BMI) ≤20 or \>40 kg/m\^2.
* 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 predisposed to MTC (e.g. multiple endocrine neoplasia syndromes).
* Contraindication related to metformin (for participant receiving this treatment), insulin glargine, insulin glulisine or lixisenatide.
* Participants with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease.
* At screening, amylase and/or lipase \>3 times the upper limit of the normal laboratory range (ULN).
* At screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 ULN.
* 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 participant's potential participation in a clinical trial.