The efficacy and safety of seven regimens based on metformin (placebo plus metformin, dapagliflozin plus metformin, vildagliptin plus metformin, saxagliptin plus metformin, empagliflozin plus metformin, exenatide plus metformin and sitagliptin plus metformin) on type 2 diabetes (T2D) were compared based on network meta-analysis. PubMed, Embase and Cochrane Library were applied in the computer-based retrieval process. Randomized controlled trials (RCTs) which were related with the above seven regimens based on metformin in the treatment of T2D were included in this study. Network meta-analysis merged the direct and indirect comparison evidence for the estimation of the weighted mean difference (WMD), odd ratios (ORs) and surface under the cumulative sequencing ranking curve (SUCRA) values. Eight eligible RCTs were applied in this network meta-analysis. The results demonstrated that: in terms of efficacy, the glycated hemoglobin (HbA1c) levels of T2D patients receiving vildagliptin plus metformin were relatively lower when compared with placebo plus metformin (WMD=−1.95, 95%CI=−3.70–−0.23); in comparison with exenatide plus metformin, the triglyceride level in T2D patients taking vildagliptin plus metformin remained relatively lower (WMD=−1.36, 95%CI=−2.64–−0.01). In terms of safety, the rate of adverse events in patients with T2D who received empagliflozin plus metformin was relatively lower when compared with saxagliptin plus metformin (OR=0.37, 95%CI=0.14–0.98). Furthermore, the SUCRA value of vildagliptin plus metformin was comparatively higher in efficacy, and that the SUCRA value of saxagliptin plus metformin was relatively lower in safety. The efficacy of vildagliptin plus metformin in patients with T2D is relatively better, while the safety of saxagliptin plus metformin in patients with T2D is relatively poorer.