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

Conditions: Type 2 Diabetes Mellitus

Summary: primary objective: to demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (frc) versus glp-1 receptor agonist (glp-1 ra) in hemoglobin a1c (hba1c) change. secondary objectives: to compare the overall efficacy and safety of the insulin glargine/lixisenatide frc to glp-1 ra on top of metformin (with or without pioglitazone, with or without sodium-glucose co-transporter 2 \[sglt2\] inhibitor) in participants with type 2 diabetes. to evaluate safety, efficacy and other endpoints of frc up to the end of the extension period.

the maximum duration for glp1-ra participants was approximately 29 weeks: up to 2 week screening period, a 26 week treatment period (either randomized or uncontrolled), and a 3 or 9 day post-treatment safety follow-up period. maximum duration for frc participants was approximately 55 weeks: 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 outcome measures were assessed at the end of the extension period.

Eligibility criteria:
inclusion criteria : * participants with type 2 diabetes mellitus diagnosed at least 1 year prior to screening visit. * participants who were treated with one of the following glp-1 receptor agonists for at least 4 months prior to screening visit 1 (v1), and with stable dose for at least 3 months prior to screening visit (v1): * liraglutide (victoza®) 1.8 milligram (mg) qd or 1.2 mg qd, if the 1.8 mg qd dose was not well tolerated according to the investigator's judgment or * exenatide (byetta®) 10 microgram (µg) bid or of 5 µg bid, if 10 µg bid dose was not well tolerated according to the investigator's judgment in combination with metformin (daily dose greater than equal to \[\>=\] 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 participants who were 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 was not well tolerated according to investigator's judgment, * dulaglutide (trulicity®) 1.5 mg qw or 0.75 mg qw, if 1.5 mg qw was 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 \ 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 was 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 millimoles per litre \[mmol/l\]), * 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. * participant who had renal function impairment with estimated glomerular filtration rate \<30ml/min/1.73m\^2 (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 \ 40 kg/m\^2. exclusion criteria for the extension period: * participants in the frc arm with a rescue therapy and hba1c \>8% at week 22. * participants in the frc arm who discontinued prematurely from frc treatment before week 26. * participants 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.