Pharmacodynamic Effects of Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin

An Open-label, Randomized, Three-parallel-group Study on Pharmacodynamic Effects of 8-week QD Treatment With Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin

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).

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

Inclusion criteria :

• Participants with T2DM diagnosed at least 1 year before the screening visit.
• Treatment with neutral protamine hagedorn (NPH) or insulin glargine for at least 3 months and at a stable dose (±20%) of at least 10 IU/day (for at least 2 months prior to screening) alone or combined with a stable dose of metformin with or without dipeptidyl peptidase 4 (DPP-4) inhibitor or sulfonylurea.
• Glycosylated hemoglobin (HbA1c) ≥6.5 and ≤9.5%.
• Body mass index (BMI) between 20 and 40 kg/m^2.

Exclusion criteria:

• Pregnant women or breastfeeding women.
• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to, gastroparesis and gastroesophageal reflux disease requiring medical treatment within 6 months prior to the time of screening.
• Any previous treatment with lixisenatide or participation in a previous study with lixisenatide (AVE0010), and any previous treatment with liraglutide stopped for safety concern or lack of efficacy.
• Allergic reaction to any glucagon-like peptide-1 (GLP-1) agonist in the past (eg, exenatide) or to metacresol.
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease.
• Personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC.

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