OBJECTIVES: Exenatide is increasingly used in obese or overweight patients with diabetes. However, its safety profile and effects on weight loss in nondiabetic obese or overweight population remain unclear. We aimed to evaluate efficacy and safety of exenatide in obese or overweight participants without diabetes. METHODS: We searched up to January 2016 in MEDLINE (Ovid SP),EMBASE (Ovid SP), Cochrane Central Register of Controlled Trials (CENTRAL), some Chinese databases and ClinicalTrials.gov for randomized controlled trials (RCTs) investigating exenatide in obese or overweight participants without diabetes. The primary outcomes included body weight and body mass index (BMI). We pooled data to calculate the mean differences (MDs) with their 95% confidence intervals (CIs). We assessed overall evidence quality of BMI reduction and weight los according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Six randomized controlled trials involving 362 patients were included in the meta- analysis. The follow-up duration ranged from12 to 24 weeks. Compared with control group, a larger body weight loss (MD:−%CI: −− patients in exenatide group. Exenatide also elicited a greater reduction in BMI (MD: −− to −−−− with the control. No significant benefits were showed in exenatide group in terms of blood pressure and lipid profiles. Gastrointestinal adverse events were mostly common during the treatment of exenatide. CONCLUSIONS: Exenatide could significantly reduce body weight in obese or overweight participants without diabetes, and might be a safe alternative GLP-1 receptor agonist for weight control in such patients. Larger randomized trials with longer follow-up duration are required to confirm the effectiveness and safety of exenatide.