ObjectiveTo evaluate the efficacy and safety of piolitazone combined with metformin for type 2 diabetes mellitus. MethodsThe Cochrane Library (Issue 9, 2015), PubMed, EMbase, CNKI, WanFang Data and VIP databases were searched up to September 2015 for randomized controlled trials (RCTs) about pioglitazone combined with metformin versus sulfonylurea combined with metformin for type 2 diabetes mellitus. Two reviewers independently screened literature, extracted date, and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 7 RCTs involving 3 005 patients were included. The results of metaanalysis showed that when the course of treatment was ≤24 weeks, no significant difference was found in the level of HbA1c between the piolitazone plus metformin group and the sulphonylurea plus metformin group (MD=-0.04, 95%CI -0.26 to 0.19, P=0.74), but the piolitazone plus metformin group had lower risk of hypoglycemia (RR=0.39, 95%CI 0.15 to 1.01, P=0.05); when the course of treatment >24 weeks, only one RCT was included, we didn't conduct pool analysis. ConclusionPiolitazone combined with metformin has similar effect to sulphonylurea combined with metformin in controlling blood sugar, but piolitazone combined with metformin has lower incidence of hypoglycemia. Due to limited quality and quantity of the included studies, the above conclusion need to be verified by more high quality studies.