evaluation of insulin glargine/lixisenatide fixed ratio combination in patients with type 2 diabetes insufficiently controlled with oral antidiabetic drug(s)

Conditions: Type 2 Diabetes Mellitus

Summary: 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: * \ 11% for patients previously treated with metformin alone; * \ 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) : \ 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.