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

A Randomized, 24 Week, Active-controlled, Open-label, 3-arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of iGlarLixi to Insulin Glargine and Lixisenatide in Type 2 Diabetes Mellitus Patients 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.

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.