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

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.

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.