OBJECTIVE： To systematically evaluate therapeutic efficacy and safety of long-acting glucagon like peptide-1 （GLP-1） receptor agonist Semaglutide vs. placebo or other glucose-lowering drugs in the treatment of type 2 diabetes mellitus （T2DM）， and to provide evidence-based reference for T2DM in clinic. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane library， randomized controlled trials （RCT） about Semaglutide （trial group） vs. placebo or other glucose-lowering drugs （control group） in the treatment of T2DM were selected during the establishment of database to Sept. 2018. After data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was performed for HbA1c level and compliance rate， fasting plasma glucose （FPG） level， systolic blood pressure （SBP）， diastolic blood pressure （DBP）， body mass index （BMI）， body weight pulse frequency level， the incidence of hypoglycemia and gastrointestinal reaction by using Rev Man 5.3 software.  RESULTS： A total of 12 RCTs involving 9 966 patients were included. The results of Meta-analysis showed that compared with control group， trial group could effectively decrease the levels of HbA1c [MD＝－1.03， 95％CI（－1.22，－0.85）， P＜0.001] and FPG [MD＝－1.14， 95％CI（－1.53，－0.76）， P＜0.001]， increase compliance rate of HbA1c [RD＝0.40， 95％CI（0.31，0.49）， P＜0.001]， reduce SBP [MD＝－2.61， 95％CI （－3.23， －1.98）， P＜0.001] and DBP [MD＝－0.56， 95％CI     （－0.96， －0.16）， P＝0.006]， decrease BMI [MD＝－1.25， 95％CI （－1.51， －0.99）， P＜0.001] and body weight [MD＝     －3.60， 95％CI（－4.24， －2.96）， P＜0.001]， increase pulse frequency [MD＝2.16， 95％CI （1.51， 2.81）， P＜0.001]. The major adverse drug reactions were gastrointestinal reaction； the incidence of gastrointestinal reaction was higher than control group [RD＝0.20， 95％CI（0.15，0.26）， P＜0.001]， but there was no statistical significance in the incidence of hypoglycemia events between 2 groups [RD＝0.00， 95％CI（－0.01，0.02）， P＝0.44]. CONCLUSIONS： Semaglutide can significantly decrease HbA1c， FPG， body weight， blood pressure and increase pulse frequency in T2DM patients， and increase the compliance rate of HbA1c. Although the incidence of gastrointestinal reaction is higher than control group， but the risk of hypoglycemia is not higher， indicating Semaglutide is well tolerated and safe.