OBJECTIVE: To evaluate the effectiveness and safety of different Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating type 2 diabetes mellitus (T2DM) with overweight/obesity using a systematic review and network meta-analysis. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science up to December 20, 2024, for randomized controlled trials (RCTs) involving T2DM patients with overweight/obesity treated with GLP-1RAs, with the control group receiving either a placebo or another GLP-1RA. We conducted a network meta-analysis assessed evidence using CINeMA. RESULTS: A total of 4548 articles were retrieved, and 41 RCTs were included, comprising 15,126 patients and 13 different GLP-1RAs. Tirzepatide showed superior effects in lowering blood glucose (Compared with placebo, increased glycated hemoglobin: -1.64 (-1.94, -1.35), increased fasting blood glucose: -2.10 (-2.95, -1.25)) and weight loss (Compared with placebo, increased weight: -9.89 (-11.29, -8.49), rincreased BMI: -3.85 (-4.71, -2.99)). However, clinical efficacy of GLP-1RAs in lipid levels, blood pressure, and pancreatic function was not widely observed. Adverse reactions were significant with GLP-1RAs, but overall acceptable. CONCLUSION: GLP-1RAs demonstrate efficacy and safety in T2DM patients with overweight/obesity, with certain advantages over other drugs. However, due to limitations in the number and quality of included studies, conclusions should be interpreted with caution.