Objective: The aim of this study was to compare the efficacy and safety of metformin/thiazolidinediones (TZDs) / glucagon-like peptide 1 (GLP-1) analogs (triple therapy) with conventional glucose-lowering therapy(conventional therapy) for patients with type 2 diabetes and metabolic syndrome. Methods: A prospective randomized-controlled 26-week study was carried out. A total of 82 patients with type 2 diabetes and metabolic syndrome were randomized to receive either triple therapy protocal or just conventional therapy, altogether with 41 cases in each group. Results: HbA_1C value was significantly reduced in triple therapy group versus the conventional therapy group [(2.23±1.75)% vs (1.48±1.59)%, P<0.05]. Values of body mass index, waist circumference, and visceral fat area were significantly reduced in triple therapy group as compared to those of conventional therapy group [(2.50±1.81 vs 0.92±1.82)kg/m², (6.75±4.92 vs 1.66±3.25)cm, (24.10±19.10 vs 10.02±20.10)cm², all P<0.01, respectively]. Control rates of HbA_1C and fasting plasma glucose for triple therapy were higher than those for conventional therapy (both P<0.05). No hypoglycemia occurred in triple therapy group. Subjects receiving triple therapy experienced more frequent gastrointestinal side effects than those in conventional therapy group (18.87% vs 3.92%, P<0.05). The most common side event was mild nausea (90%). Conclusion Combination therapy with metformin/TZDs/GLP-1 analogs had statistically significant advantages in the control of body weight, waist circumference, and visceral fat area in addition to the control of blood glucose over conventional glucose-lowering therapy in our patient cohort, it seems to be an optimized therapeutic regimen for patients with type 2 diabete and metabolic syndrome.