Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (FRC) Versus GLP-1 Receptor Agonist in Patients With Type 2 Diabetes, With a FRC Extension Period

The maximum duration for GLP1-RA patients will be approximately 29 weeks: an up to 2 week
screening period, a 26 week treatment period (either randomized or uncontrolled), and a 3 or
9 day post-treatment safety followup period.

Maximum duration for FRC patients will be approximately 55 weeks: an up to 2- week screening
period, a 26-week randomized treatment period, a 26-week extension period and a 3-day
post-treatment safety follow-up period. All primary and secondary efficacy, safety and other
endpoints will be also assessed at the end of the extension period.

Inclusion criteria :

- Patients with type 2 diabetes mellitus diagnosed at least 1 year prior to screening
visit.

- Patients who have been treated with one of the following glucagon-like peptide 1
(GLP-1) receptor agonists for at least 4 months prior to screening visit (V1), and
with stable dose for at least 3 months prior to screening visit (V1):

- Liraglutide (Victoza®) 1.8 mg QD or 1.2 mg QD, if the 1.8 mg QD dose is not well
tolerated according to the Investigator's judgment or

- Exenatide (Byetta®) 10 µg BID or of 5 µg BID, if 10 µg BID dose is not well tolerated
according to the Investigator's judgment in combination with metformin (daily dose
≥1500 mg/day or maximum tolerated dose [MTD]), with or without pioglitazone, with or
without SGLT2 inhibitor, all at stable dose for at least 3 months prior to screening.

or

Patients who have been treated with stable dose of one of the following GLP-1 receptor
agonists for at least 6 months prior to screening visit (V1):

- Exenatide extended-release (Bydureon®) 2 mg once weekly (QW), if well tolerated
according to Investigator's judgment,

- Albiglutide (Tanzeum®) 50 mg QW or 30 mg QW, if 50 mg QW is not well tolerated
according to Investigator's judgment,

- Dulaglutide (Trulicity®) 1.5 mg QW or 0.75 mg QW, if 1.5 mg QW is not well tolerated
according to Investigator's judgment in combination with metformin (daily dose ≥1500
mg/day or MTD), with or without pioglitazone, with or without SGLT2 inhibitor, all at
stable dose for at least 3 months prior to screening;

- Signed written informed consent.

Exclusion criteria:

- At screening visit, age <18.

- Screening HbA1c <7% and >9%.

- Pregnancy or lactation, women of childbearing potential with no effective
contraceptive method.

- Any use of antidiabetic drugs within 3 months prior to the screening visit other than
those described in the inclusion criteria.

- Previous treatment with insulin in the year prior to screening visit (note: short-term
treatment with insulin [≤10 days] due to intercurrent illness including gestational
diabetes is allowed at the discretion of the study physician).

- Laboratory findings at the time of screening, including:

- Fasting plasma glucose (FPG) >250 mg/dL (13.9 mmol/L),

- Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN),

- Alanine transaminase or aspartate transaminase >3 ULN,

- Calcitonin ≥20 pg/mL (5.9 pmol/L),

- Positive pregnancy test.

- Patient who has renal function impairment with estimated glomerular filtration rate
<30mL/min/1.73m2 (using the Modification of Diet in Renal Disease formula) or
end-stage renal disease.

- Contraindication to use of insulin glargine, or lixisenatide or GLP-1 receptor agonist
(Victoza®, Byetta®, Bydureon®, Tanzeum® or Trulicity®) according to local labeling.

- Any contraindication to metformin or pioglitazone or SGLT2 inhibitor use, according to
local labeling.

- History of hypersensitivity to insulin glargine, or to any of the excipients.

- History of allergic reaction to any GLP-1 receptor agonist or to meta-cresol.

- Personal or immediate family history of medullary thyroid cancer (MTC) or genetic
condition that predisposes to MTC (eg, multiple endocrine neoplasia type 2 syndromes).

- 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.

- Body mass index ≤20 or >40 kg/m^2.

Exclusion criteria for the extension period:

- Patients in the FRC arm with a rescue therapy and HbA1c >8% at week 22.

- Patients in the FRC arm who discontinued prematurely from FRC treatment before week
26.

- Patients in the GLP-1 RA treatment arm after randomization.

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