24-week Study Comparing Lixisenatide (AVE0010) to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50

Inclusion criteria

• Patients with type 2 diabetes mellitus, as defined by WHO (25), diagnosed for at least 1 year at the time of screening visit, insufficiently controlled with metformin at a stable dose of at least 1.5 g/day for at least 3 months prior to the screening visit.
• Patients with obesity (BMI ≥ 30kg/m2) and aged from 18 years to less than 50 years.

Exclusion criteria

• HbA1c < 7.0% or HbA1c >10% at screening
• Type 1 diabetes mellitus
• Pregnancy or lactation
• Women of childbearing potential with no effective contraceptive method
• Fasting Plasma Glucose at screening > 250 mg/dL (> 13.9 mmol/L)
• Weight change of more than 5 kg during the 3 months preceding the screening visit
• History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g. multiple endocrine neoplasia syndromes),
• History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
• Hemoglobinopathy or hemolytic anemia or receipt of blood or plasma products within 3 months prior to the time of screening
• Within the last 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization
• Known history of drug or alcohol abuse within 6 months prior to the time of screening
• Any clinically significant abnormality identified on physical examination, laboratory tests, ECG or vital signs at the time of screening that in the judgment of the investigator or any sub investigator would preclude safe completion of the study or constrains efficacy assessment such as major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require laser treatment within the study period.
• Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure > 180 mmHg or > 110 mmHg, respectively

• Laboratory findings at the time of screening:

  • Amylase and/or lipase > 3 times the upper limit of the normal laboratory range
  • Total bilirubin: > 1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome)
  • Hemoglobin < 11 g/dL and/or neutrophils < 1,500/mm3 and/or platelets < 100,000/mm3
  • Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody
  • Positive serum pregnancy test in females of childbearing potential
  • Calcitonin ≥ 20 pg/mL (5.9 pml/L)
• Use of other oral or injectable antidiabetic or hypoglycemic agents than metformin (e.g., sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, exenatide, DPP-IV inhibitors, insulin etc.) within 3 months prior to the time of screening
• Unstable diet or unstable anti-obesity treatment within 3 months prior to the time of screening
• Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening
• Use of any investigational drug within 3 months prior to screening 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 AVE0010 (e.g. participation in a previous study with AVE0010)
• Allergic reaction to any GLP 1-agonist in the past (e.g. exenatide, liraglutide) or to metacresol
• History of a serious hypersensitivity reaction to sitagliptin.
• Moderate or severe renal impairment (creatinine clearance inferior to 50 ml/mn)

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