DRUG
Lixisenatide (AVE0010)
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
Status
Completed
Phase
Phase 3
Enrollment
319
Locations
92
Results
Posted
Publications
0
Study summary
The purpose of this study is to evaluate benefits and risks of lixisenatide (AVE0010), in comparison to sitagliptin, as an add-on treatment to metformin, in obese (body mass index \[BMI\] greater than or equal to 30 kilogram per square meter \[kg/m\^2\]) type 2 diabetic patients less than 50 years of age, over a period of 24 weeks of treatment. The primary objective of this study is to assess the efficacy of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on a composite endpoint of glycemic control in terms of glycosylated hemoglobin (HbA1c) and body weight, at Week 24. Secondary objectives are to assess the effects of lixisenatide, in comparison to sitagliptin, as an add-on treatment to metformin on absolute changes in HbA1c values and body weight; fasting plasma glucose (FPG); plasma glucose, insulin, C-peptide, glucagon, and proinsulin during a 2-hour standardized meal test; insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA-IR); beta cell function assessed by homeostatic model assessment of beta-cell function (HOMA-beta); to evaluate safety, tolerability, and anti-lixisenatide antibody development.
Interventions
DRUG
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
DRUG
Self-administered by subcutaneous injections once daily within the hour preceding breakfast.
DEVICE
DRUG
Administered orally once a day in the morning with or without food at approximately the same time each day.
DRUG
Administered orally once a day in the morning with or without food at approximately the same time each day.
DRUG
Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.
Timeline
First posted
Sep 15, 2009
Study start
Aug 2009
Primary completion
Mar 2011
Study completion
Mar 2011
Results posted
Oct 11, 2016
Registry updated
Oct 11, 2016
Outcomes
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% and at Least 5% Weight Loss From Baseline at Week 24
Time frame · Week 24
Percentage of patients who met both criteria (HbA1c \<7% at Week 24 and at least 5% weight loss from baseline at Week 24) is reported. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Absolute Change From Baseline in HbA1c at Week 24
Time frame · Baseline, Week 24
Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Body Weight at Week 24
Time frame · Baseline, Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) at Week 24
Time frame · Baseline, Week 24
The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Time frame · Baseline, Week 24
Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Glucose Excursion at Week 24
Time frame · Baseline, Week 24
Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Plasma Insulin (FPI) and 2-hour Postprandial Plasma Insulin (PPI) at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting plasma insulin and 2-hour post prandial plasma insulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of the study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting C-peptide and 2-hour Postprandial C-peptide at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting C-peptide and 2-hour postprandial C-peptide by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Glucagon and 2-hour Postprandial Glucagon at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting glucagon and 2-hour postprandial glucagon by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Fasting Proinsulin and 2-hour Postprandial Proinsulin at Week 24
Time frame · Baseline, Week 24
Change was calculated for fasting proinsulin and 2-hour postprandial proinsulin by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of the study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Change From Baseline in Insulin Resistance Assessed by Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) at Week 24
Time frame · Baseline, Week 24
HOMA-IR was derived from FPG and FPI as: (FPI \[micro units per milliliter\]\*FPG \[mmol/L\]) divided by 22.5. Change was calculated for HOMA-IR by subtracting the baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest.
Eligibility
Inclusion criteria * Type 2 diabetes mellitus, 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 gram/day (g/day) for at least 3 months prior to the screening visit * Patients with obesity (BMI greater than equal to \[\>=\] 30 kg/m\^2) and aged from 18 years to less than 50 years Exclusion criteria * HbA1c less than (\<) 7.0 percent (%) or HbA1c greater than (\>) 10% at screening * Type 1 diabetes mellitus * Pregnant or breastfeeding women or women of childbearing potential with no effective contraceptive method * FPG at screening \>250 milligram/deciliter (mg/dL) (\>13.9 millimole/ liter \[mmol/L\]) * 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 (for example, 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, electrocardiogram (ECG) or vital signs at the time of screening that in the judgment of the investigator or any sub-investigator could have precludes 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 millimeter of mercury (mmHg) or \>110 mmHg, respectively * Laboratory findings at the time of screening : Amylase and/or lipase \>3 times the upper limit of normal (ULN) laboratory range; alanine aminotransferase (ALT): \>3 times ULN; total bilirubin: \>1.5 times ULN (except in case of Gilbert's syndrome); hemoglobin \<11 gram/deciliter and/or neutrophils \<1500 per cubic millimeter (mm\^3) and/or platelets \<100 000/mm\^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCAb), positive serum pregnancy test in females of childbearing potential, and calcitonin \>=20 picogram per milliliter (pg/mL) (5.9 picomole per liter) * Patients who are considered by the investigator or any sub-investigator as inappropriate for the study for any reason (for example, impossibility to meet specific protocol requirements \[such as scheduled visits, being able to do self-injections\], likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol, investigator or any sub-investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol) * Use of other oral or injectable antidiabetic or hypoglycemic agents than metformin (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, exenatide, dipeptidyl peptidase IV (DPP-IV) inhibitors, insulin) within 3 months prior to the time of screening * History of bariatric surgery, anti-obesity treatment, or unstable diet 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, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening * Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide) * Allergic reaction to any glucagon like peptide-1 (GLP 1) agonist in the past (for example, exenatide, liraglutide) or to metacresol * History of a serious hypersensitivity reaction to sitagliptin * Moderate or severe renal impairment (creatinine clearance inferior to 50 milliliter/minute \[mL/min\]) * Additional exclusion criteria at the end of the run-in phase: informed consent withdrawal; lack of compliance during the single-blind placebo run-in period (\>2 injections missed or \>2 capsules missed); and patient with any adverse event which could have precludes the inclusion in the study, as assessed by the investigator
Study locations
Australia · Brazil · Canada · Chile · Germany · Guatemala · Mexico · Peru · Poland · Romania · Russia · Ukraine · United States. Showing up to 24 locations stored in the fast local snapshot.
Sanofi-Aventis Investigational Site Number 840019
Montgomery, Alabama, United States
Sanofi-Aventis Investigational Site Number 840003
Muscle Shoals, Alabama, United States
Sanofi-Aventis Investigational Site Number 840022
Mesa, Arizona, United States
Sanofi-Aventis Investigational Site Number 840011
Anaheim, California, United States
Sanofi-Aventis Investigational Site Number 840014
Paramount, California, United States
Sanofi-Aventis Investigational Site Number 840027
Redlands, California, United States
Sanofi-Aventis Investigational Site Number 840021
Augusta, Georgia, United States
Sanofi-Aventis Investigational Site Number 840007
Roswell, Georgia, United States
Sanofi-Aventis Investigational Site Number 840016
Chicago, Illinois, United States
Sanofi-Aventis Investigational Site Number 840018
Chicago, Illinois, United States
Sanofi-Aventis Investigational Site Number 840001
Evansville, Indiana, United States
Sanofi-Aventis Investigational Site Number 840002
Baton Rouge, Louisiana, United States
Sanofi-Aventis Investigational Site Number 840031
Clarkston, Michigan, United States
Sanofi-Aventis Investigational Site Number 840020
Florissant, Missouri, United States
Sanofi-Aventis Investigational Site Number 840006
Butte, Montana, United States
Sanofi-Aventis Investigational Site Number 840026
Perrysburg, Ohio, United States
Sanofi-Aventis Investigational Site Number 840004
Medford, Oregon, United States
Sanofi-Aventis Investigational Site Number 840025
Altoona, Pennsylvania, United States
Sanofi-Aventis Investigational Site Number 840009
Brentwood, Tennessee, United States
Sanofi-Aventis Investigational Site Number 840008
Dallas, Texas, United States
Sanofi-Aventis Investigational Site Number 840010
San Antonio, Texas, United States
Sanofi-Aventis Investigational Site Number 036006
Adelaide, Australia
Sanofi-Aventis Investigational Site Number 036001
Box Hill, Australia
Sanofi-Aventis Investigational Site Number 036004
Elizabeth Vale, Australia
Publications
No PMID-linked publications were present in this registry snapshot.
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