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Objective: The aim of this study was to evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). Methods: We searched clinical trials indexed in PubMed, Embase, CENTRAL, Web of Science, and Scopus from inception through December 3, 2018. A meta-analysis was conducted of trials involving patients receiving SGLT2 inhibitors and GLP-1 agonists using Stata 12.0 software. Results: A total of 9 clinical trials, including 5 randomized controlled trials (RCTs), that enrolled 1369 participants were identified for meta-analysis. Compared with the control/placebo group, the combination therapy group had significantly reduced fasting plasma glucose level by 0.78 mmol/L (95% confidence interval [CI]: -1.36, -0.2), 2-h postprandial glucose level by 0.47mmol/L (95% CI: -0.69, -0.24), glycosylated hemoglobin (HbA1c) by 0.73% (95% CI: -1.45, 0); body weight that was lower by 0.39 kg (95% CI: -0.59, -0.18) (4 non-randomized controlled trials indicated a larger reduction in body weight of 3.53 kg), and systolic blood pressure (SBP) that was lower by 0.26 mmHg (95% CI: -0.40, -0.11). The total incidence of adverse events (AEs) and genital and urinary infections in the therapy group did not significantly differ from those in the control group, with relative risks (RRs) of 1.06 (95% CI: 0.96, 1.17) and 1.19 (95% CI: 0.69, 2.07), respectively. An increased incidence of hypoglycemia was seen in the combination therapy group (RR=2.49; 95% CI: 1.40, 4.45). Conclusions: SGLT2 inhibitor and GLP-1 agonist combination treatment improved glycemic control, reduced body weight, and decreased SBP without an increase in total AEs or genital and urinary infections in patients with T2DM. However, the risk of hypoglycemia should be carefully monitored in future clinical trials. Disclosure M. Guo: None. J. Gu: None. J. Li: None. Y. Xu: None. Funding National Natural Science Foundation of China (81800741)