Efficacy and Safety of LixiLan Versus Insulin Glargine Alone Both With Metformin in Japanese With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Drugs

Primary Objective:

To compare LixiLan to insulin glargine in glycated hemoglobin (HbA1c) change from baseline to week 26 in patients with type 2 diabetes mellitus.

Secondary Objective:

To compare overall efficacy and safety of LixiLan to insulin glargine over 26 weeks in patients with type 2 diabetes mellitus.

The maximum study duration per patient will be approximately 41 weeks: an up to 14-week screening period (consisting of an up to 2-week screening phase and a 12-week run-in phase), a 26-week randomized treatment period, and a 3-day post-treatment safety follow-up period.

Eligibility Criteria:
Inclusion criteria :

* Patient with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit (V1).
* Patient treated with a stable, once a day basal insulin regimen (ie, type of insulin and time/frequency of the injection), for at least 3 months before the screening visit.
* The total daily basal insulin dose should be stable (± 20%) and \<15 U/day for at least 1 month before the screening visit.
* Patient receiving 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months before the screening visit. The OADs can be 1 to 2 out of:
* Metformin;
* Sulfonylurea (SU);
* Glinide;
* Dipeptidyl-peptidase-4 (DPP-4) inhibitor;
* Sodium glucose co-transporter 2 (SGLT2) inhibitor;
* Alpha glucosidase inhibitor (alpha-GI).
* Signed written informed consent.

Exclusion criteria:

* Age \<20 years at screening visit.
* HbA1c at screening visit \<7.5% or \>9.5%.
* Fasting plasma glucose (FPG) \>180 mg/dL (10.0 mmol/L) at screening visit.
* Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
* Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria in the 3 months before screening visit.
* Previous use of insulin regimen other than basal insulin, eg, prandial or pre-mixed insulin.

Note: Short-term treatment (≤10 days) due to intercurrent illness including gestational diabetes is allowed at the discretion of the Investigator.

* Use of thiazolidinedione (TZD) within 6 months prior to screening visit.
* History of discontinuation of a previous treatment with a glucagon-like peptide-1(GLP-1) receptor agonist due to safety/ tolerability issues or lack of efficacy.
* Laboratory findings at the screening visit; including:
* Amylase and/or lipase \>3 times the upper limit of the normal (ULN) laboratory range;
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 ULN;
* Calcitonin ≥20 pg/mL (5.9 pmol/L);
* Positive serum pregnancy test.
* Any contraindication to metformin use according to local labeling.
* History of hypersensitivity to any GLP-1 receptor agonist or to metacresol.
* Contraindication to use of insulin glargine or lixisenatide according to local labeling. History of hypersensitivity to insulin glargine or to any of the excipients.
* Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes).
* History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has now been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, stomach/gastric surgery.
* Exclusion criteria for randomization at the end of the run-in phase:
* HbA1c \<7.5% or \>9.5% at visit 6 (Week -1).
* Mean fasting self monitored plasma glucose (SMPG) \>160 mg/dL (8.9 mmol/L), calculated from all available (minimum of 4 self-measurements) values during the 7 days prior to randomization.

Note:fasting SMPG on the day of randomization can be included if assessed before randomization.

* Average insulin glargine daily dose ≥15 U/day or \<5U/day calculated for the last 3 days before Visit 7.
* Metformin total daily dose \<750 mg/day.
* Amylase and/or lipase \>3 ULN at Visit 6 (Week -1).

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