Conditions: Type 2 Diabetes Mellitus
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 142
Healthy volunteers: no

Brief summary:
Primary Objective:

\- To investigate the effects of repeated subcutaneous doses of lixisenatide 20 μg once daily (QD) as compared to liraglutide 1.2 mg QD or 1.8 mg QD in reducing post-prandial plasma glucose (PPG) assessed as area under the plasma glucose-concentration-time curve (AUC) after a standardized breakfast at the end of a 8-week treatment period in participants with type 2 diabetes mellitus (T2DM) not adequately controlled with insulin glargine (± metformin).

Secondary Objectives:

* To assess the effects of lixisenatide 20 μg QD as compared to liraglutide 1.2 QD or 1.8 mg QD after an 8-week treatment period in participants with T2DM not adequately controlled with insulin glargine (± metformin) on:

  * Post-prandial C-peptide, glucagon and appetite perceptions after a standardized breakfast,
  * Appetite perceptions after standardized dinner,
  * Gastric emptying after a standardized labelled test meal,
  * Fasting plasma glucose, 24-hour plasma glucose profile,
  * Glycosylated hemoglobin (HbA1c),
  * Insulin glargine dose,
  * 7-point self monitored plasma glucose (SMPG),
  * Body weight and waist circumference,
  * 24-hour heart rate and blood pressure,
* To assess lixisenatide and liraglutide safety and tolerability as add on treatment to insulin glargine (± metformin).

Detailed description:
Up to 2-week screening period

* A run-in period of 12 weeks at maximum including a forced titration with insulin glargine up to 11 weeks and 1 baseline pharmacodynamic assessment week
* A 8-week treatment(s) period(s) up to Day 57
* Follow-up: 7 ±2 days after the last treatment day
* Total study duration approximately 14 weeks up to 23 weeks

Arms:
arm 1: Subcutaneous injection of lixisenatide10 μg once daily (QD) for 2 weeks followed by 20 μg QD for 6 weeks under fasted conditions, on top of insulin glargine with or without metformin. arm 2: Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for 7 weeks under fasted conditions, on top of insulin glargine with or without metformin. arm 3: Subcutaneous injection of liraglutide 0.6 mg QD for 1 week followed by 1.2 mg QD for another 1 week and 1.8 mg QD for next 6 weeks under fasted conditions, on top of insulin glargine with or without metformin.

Interventions: intervention 1: Lixisenatide (AVE0010) intervention 2: Liraglutide intervention 3: Insulin Glargine intervention 4: Metformin
Intervention descriptions: intervention 1: Pharmaceutical form: solution for injection self-administered with a pen-like injector (OptiClik®).

Route of administration: subcutaneous intervention 2: Pharmaceutical form:solution for injection

Route of administration: subcutaneous intervention 3: Doses to be adjusted to maintain a fasting self-measured plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL) intervention 4: If previously taken metformin to be continued at stable dose throughout the study

Protocol document: