pharmacodynamic effects of lixisenatide compared to liraglutide in patients with type 2 diabetes not adequately controlled with insulin glargine with or without metformin

Conditions: Type 2 Diabetes Mellitus

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).

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

Eligibility criteria:
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.