Introduction The present study aimed to evaluate the effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on clinical and safety outcomes including glycemic control and cardiometabolic indicators using network meta-analysis. Methods MEDLINE, Embase, and Cochrane Library Central Register of Controlled Trials were searched from inception through June 30, 2019. Randomized clinical trials comparing one or more of six eligible GLP-1RAs with placebo or another eligible GLP-1RA were identified. We further screened studies that had 24-30 week follow-up periods and target endpoints. The primary outcome was change in hemoglobin A(1c) (HbA(1c)). Secondary outcomes included additional glycemic control indicators, cardiometabolic measures, and adverse events. Frequentist random-effect network meta-analyses were conducted for effect comparison. Results The NMA synthesized evidence from 54 studies covering 23,209 patients and 18 GLP-1RA regimens. All included GLP-1RA regimens except liraglutide 0.3 mg once weekly (QW) significantly lowered HbA(1c) after 24-30 weeks compared with placebo. The pairwise comparison of HbA(1c)-lowering effect showed that dulaglutide 0.75 mg QW, dulaglutide 1.5 mg QW, exenatide 2 mg QW, liraglutide 0.9 mg QW, liraglutide 1.2 mg QW, liraglutide 1.8 mg QW, loxenatide 100 mu g QW, and loxenatide 200 mu g QW were not significantly outperformed by any of the other regimens. The effects on blood pressure, weight, and lipids were relatively mixed. The GLP-1RA regimens had comparable safety profiles with regard to hypoglycemia and adverse events. Conclusion Regimens of GLP-1RAs had differential glycemic control and cardiometabolic effectiveness. Policymaking and patient-centric clinical decisions should take into consideration the comparative effectiveness profiles.