Comparison of the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine in Patients With Type 2 Diabetes Insufficiently Controlled on Basal Insulin

The maximum study duration per patient will be approximately 33 weeks: an up to 2-week screening period (it can be exceptionally extended up to one additional week), a 30-week, open label randomized treatment period comparing iGlarLixi to insulin glargine (± metformin for both treatments), 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 and treated with basal insulin for at least 6 months before screening visit (V1).
• Patients who have been treated with a stable basal insulin regimen (ie, type of insulin and time/frequency of the injection), for at least 3 months before screening visit (V1).
• Stable total daily basal insulin dose (±20 %) in the range of 10 and 25 U/day for at least 2 months before screening visit (V1). Total daily dose should be within the range of 10-25 U, both inclusive, on the day of screening, but individual fluctuations of ±20% within 2 months prior to screening are acceptable.
• For patients receiving basal insulin AND 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months prior to screening. The OAD(s) can be 1 to 2 out of:
• Metformin (≥1500 mg/day or maximal tolerated dose).
• Sulfonylurea (SU)/glinide.
• Alpha-glucosidase inhibitor (alpha-GI).
• Sodium-glucose co-transporter 2 (SGLT2) inhibitor.
• Dipeptidyl-peptidase-4 (DPP-4) inhibitor.
• Fasting plasma glucose (FPG) ≤160 mg/dL (8.9 mmol/L) at screening visit (V1) (can be repeated once to confirm).
• Signed written informed consent.

Exclusion criteria

• Age <18 years at screening visit (V1).
• Screening glycated hemoglobin A1c(HbA1c) <7.0% or >10.5%.
• History of hypoglycemia unawareness.
• History of metabolic acidosis, including diabetic ketoacidosis within one 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 use of insulin regimen other than basal insulin, eg, prandial or pre-mixed insulin, within one year prior to screening (Note: Short term treatment [≤10 days] due to intercurrent illness is allowed).
• History of discontinuation of a previous treatment with glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) due to safety/tolerability reason 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 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 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:
• 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 test for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibody (HCAb).
• Positive urine pregnancy test in female of childbearing potential.
• For patient not treated with metformin at screening: severe renal function impairment with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 or end-stage renal disease.
• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (ie, worsening) or not controlled (ie, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening visit; or history of surgery affecting gastric emptying.
• 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).
• Mean fasting self-monitored plasma glucose (SMPG) is >160 mg/dL (8.9 mmol/L), calculated from all available (minimum of 4 self-measurements) values during the 7 days prior to randomization.

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