Objective To determine whether treatment with agonists of glucagon-like peptide-1 receptor (GLP-1R) result in weight loss in overweight or obese patients with or without type 2 diabetes mellitus.Design Systematic review with meta-analyses.Data sources Electronic searches (Cochrane Library, Medline, Embase, and Web of Science) and manual searches (up to May 2011).Review methods Randomised controlled trials of adult participants with a body mass index of 25 or higher; with or without type 2 diabetes mellitus; and who received exenatide twice daily, exenatide once weekly, or liraglutide once daily at clinically relevant doses for at least 20 weeks. Control interventions assessed were placebo, oral antidiabetic drugs, or insulin.Data extraction Three authors independently extracted data. We used random effects models for the primary meta-analyses. We also did subgroup, sensitivity, regression, and sequential analyses to evaluate sources of intertrial heterogeneity, bias, and the robustness of results after adjusting for multiple testing and random errors.Results 25 trials were included in the analysis. GLP-1R agonist groups achieved a greater weight loss than control groups (weighted mean difference −2.9 kg, 95% confidence interval –3.6 to –2.2; 21 trials, 6411 participants). We found evidence of intertrial heterogeneity, but no evidence of bias or small study effects in regression analyses. The results were confirmed in sequential analyses. We recorded weight loss in the GLP-1R agonist groups for patients without diabetes (–3.2 kg, –4.3 to –2.1; three trials) as well as patients with diabetes (–2.8 kg, –3.4 to –2.3; 18 trials). In the overall analysis, GLP-1R agonists had beneficial effects on systolic and diastolic blood pressure, plasma concentrations of cholesterol, and glycaemic control, but did not have a significant effect on plasma concentrations of liver enzymes. GLP-1R agonists were associated with nausea, diarrhoea, and vomiting, but not with hypoglycaemia.Conclusions The present review provides evidence that treatment with GLP-1R agonists leads to weight loss in overweight or obese patients with or without type 2 diabetes mellitus.