Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes

Primary Objective:

To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine in glycated hemoglobin (HbA1c) change from baseline to Week 30.

Secondary Objective:

To compare the overall efficacy and safety of insulin glargine/lixisenatide FRC to insulin glargine (with or without metformin) over a 30 week treatment period in participants with type 2 diabetes.

Maximum duration of approximately 39 weeks: an up to 8-week screening period, a 30-week randomized treatment period and 3 days post-treatment safety follow up period.

Eligibility Criteria:
Inclusion criteria :

* Type 2 diabetes mellitus diagnosed at least 1 year before the screening visit.
* Treatment with basal insulin for at least 6 months before the screening visit.
* Stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection) for at least 3 months before the screening visit.
* Stable (plus/minus 20 percent) total daily basal insulin dose between 15 and 40 Units/day for at least 2 months prior to the screening visit.
* For participants receiving basal insulin and 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 could be 1 to 2 out of:

  * metformin (more than or equal to 1500 mg/day or maximal tolerated dose),
  * a sulfonylurea,
  * a glinide,
  * a dipeptidyl-peptidase-4 inhibitor,
  * a sodium glucose co-transporter 2 inhibitor,
* Fasting Plasma Glucose (FPG) less than or equal to 180 mg/dL(10.0 mmol/L) at screening visit for participants receiving basal insulin in combination with 2 OADs or with 1 OAD other than metformin; FPG less than or equal to 200 mg/dL (11.1 mmol/L) at screening visit for participants on basal insulin only or basal insulin plus metformin at screening visit.
* Signed written informed consent.

Exclusion criteria:

* Age under legal age of adulthood at screening visit.
* HbA1c at screening visit less than 7.5% or above 10%.
* Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
* Use of other oral or injectable glucose-lowering agents than stated in the inclusion criteria in a period of 3 months prior to screening.
* Previous use of insulin other than basal insulin eg, prandial or pre-mixed insulin, in the year prior to screening. Note: Short term treatment (≤10 days) due to intercurrent illness is allowed.
* History discontinuation of a previous treatment with Glucagon Like Peptide -1 Receptor Agonists for safety/tolerability or lack of efficacy.
* Participant who had previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide FRC or had previously received lixisenatide.
* Use of weight loss drugs within 3 months prior to screening visit.
* Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.
* History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.
* Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
* Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit.
* At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m\^2.
* At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range.
* At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN.
* At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L).
* Any contraindication to metformin use, according to local labeling, if the participant was taking metformin.
* Participant who had a renal function impairment with creatinine clearance less than 30 mL/min (using the Cockcroft and Gault formula) or end-stage renal disease for participants, not treated with metformin.

Exclusion criteria for randomization:

* HbA1c less than 7% or above 10% .
* Mean fasting SMPG calculated from the self-measurements for 7 days the week before randomization visit was above 140 mg/dL (7.8 mmol/L).
* Average insulin glargine daily dose less than 20 Units or above 50 Units (in the week before randomization visit).
* Amylase and/or lipase more than 3 ULN .

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