Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes

Inclusion criteria

• Type 2 diabetes mellitus diagnosed at least 1 year before the screening visit.
• Treatment with basal insulin for at least 6 months before the screening visit.
• Stable basal insulin regimen (i.e. type of insulin and time/frequency of the injection) for at least 3 months before the screening visit.
• Stable (plus/minus 20 percent) total daily basal insulin dose between 15 and 40 Units/day for at least 2 months prior to the screening visit.
• For participants receiving basal insulin and 1 or 2 oral anti-diabetic drugs (OADs): the OAD dose(s) must be stable during the 3 months before the screening visit. The OADs could be 1 to 2 out of:
• metformin (more than or equal to 1500 mg/day or maximal tolerated dose),
• a sulfonylurea,
• a glinide,
• a dipeptidyl-peptidase-4 inhibitor,
• a sodium glucose co-transporter 2 inhibitor,
• Fasting Plasma Glucose (FPG) less than or equal to 180 mg/dL(10.0 mmol/L) at screening visit for participants receiving basal insulin in combination with 2 OADs or with 1 OAD other than metformin; FPG less than or equal to 200 mg/dL (11.1 mmol/L) at screening visit for participants on basal insulin only or basal insulin plus metformin at screening visit.
• Signed written informed consent.

Exclusion criteria

• Age under legal age of adulthood at screening visit.
• HbA1c at screening visit less than 7.5% or above 10%.
• Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
• Use of other oral or injectable glucose-lowering agents than stated in the inclusion criteria in a period of 3 months prior to screening.
• Previous use of insulin other than basal insulin eg, prandial or pre-mixed insulin, in the year prior to screening. Note: Short term treatment (≤10 days) due to intercurrent illness is allowed.
• History discontinuation of a previous treatment with Glucagon Like Peptide -1 Receptor Agonists for safety/tolerability or lack of efficacy.
• Participant who had previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide FRC or had previously received lixisenatide.
• Use of weight loss drugs within 3 months prior to screening visit.
• Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.
• 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, stomach/gastric surgery.
• Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes).
• Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit.
• At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m^2.
• At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range.
• At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN.
• At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L).
• Any contraindication to metformin use, according to local labeling, if the participant was taking metformin.
• Participant who had a renal function impairment with creatinine clearance less than 30 mL/min (using the Cockcroft and Gault formula) or end-stage renal disease for participants, not treated with metformin.

Exclusion criteria for randomization:

• HbA1c less than 7% or above 10% .
• Mean fasting SMPG calculated from the self-measurements for 7 days the week before randomization visit was above 140 mg/dL (7.8 mmol/L).
• Average insulin glargine daily dose less than