Evaluation of Insulin Glargine/Lixisenatide Fixed Ratio Combination in Patients With Type 2 Diabetes Insufficiently Controlled With Oral Antidiabetic Drug(s)

Primary Objectives:

The co-primary objective of this study is:

* To demonstrate the superiority of iGlarLixi (fixed ratio combination of insulin glargine and lixisenatide) versus lixisenatide on glycemic control as assessed by glycated hemoglobin A1c (HbA1c) change.
* To demonstrate the non-inferiority of iGlarLixi versus insulin glargine on glycemic control as assessed by HbA1c change.

Secondary Objectives:

* To assess the effects of iGlarLixi in comparison with insulin glargine alone and lixisenatide alone.
* To assess the safety in each treatment group.

The maximum study duration per patient will be approximately 31 weeks: an up-to 6-week screening and run-in period (with an up-to 2-week screening phase and a 4-week run-in phase), followed by a 24-week randomized treatment period and a 3-day post-treatment safety follow up period.

Eligibility Criteria:
Inclusion criteria :

* Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit (V1), treated for at least 3 months prior to the screening visit (V1) with metformin alone or metformin and a second oral antidiabetic treatment that can be a sulfonylurea (SU), a glinide, an alpha-glucosidase inhibitor (alpha-GI), a dipeptidyl peptidase-4 (DPP-4) inhibitor or a sodium-glucose co transporter 2 (SGLT-2) inhibitor and who are not adequately controlled with this treatment.
* Signed written informed consent.

Exclusion criteria:

* Age \< legal age of majority at the screening visit (V1).
* Body mass index (BMI) \>40 kg/m² at screening.
* Glycated hemoglobin A1c (HbA1c) at screening visit:
* \<7.5% or \>11% for patients previously treated with metformin alone;
* \<7.0% or \>10% for patients previously treated with metformin and a second oral antidiabetic treatment.
* History of hypoglycemia unawareness.
* History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening.
* Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria within 3 months prior to screening.
* Previous treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator) within 1 year prior to screening.
* History of discontinuation of a previous treatment with glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) due to safety/tolerability reasons or lack of efficacy.
* Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to screening.
* Use of weight loss drugs within 3 months prior to screening.
* Use of any investigational drug other than specified in this protocol within 1 month or 5 half-lives, whichever is longer, prior to screening.
* Within 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization.
* Planned coronary, carotid, or peripheral artery revascularization procedures to be performed during the study period.
* Known history of drug or alcohol abuse within 6 months prior to screening.
* Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>95 mmHg.
* Laboratory findings at screening visit (V1):
* Amylase and/or lipase \>3 times the upper limit of normal (ULN) laboratory range.
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 ULN.
* Total bilirubin \>1.5 ULN (except in case of Gilbert's syndrome).
* Calcitonin ≥20 pg/mL (5.9 pmol/L).
* Hemoglobin \<10.5 g/dL and/or neutrophils \<1500/mm3 and/or platelets \<100 000/mm3.
* Positive urine pregnancy test in female of childbearing potential.
* Patient who has a severe renal function impairment with an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 or end-stage renal disease.
* History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy.
* Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
* Use of SU, glinide, alpha-GI, DPP-4 inhibitor, and SGLT-2 inhibitor after start of run-in (from V2 \[Week -4\]).
* HbA1c at V4 (Week -1) : \<7.0% or \>10%.
* Fasting plasma glucose \>250 mg/dL (13.9 mmol/L) at V4 (Week-1) (can be repeated once to confirm).
* Metformin maximal tolerated dose \<1500 mg/day.
* Amylase and/or lipase \>3 ULN at V4 (Week-1).

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