Objective To investigate clinical efficacy and safety of metformin combined with sitagliptin or pioglitazone in treatment of type 2 diabetes mellitus (T2DM).Methods Senvnty-six patients with T2DM hospitalized from January 2011 to December 2012 were randomly divided into A(n =40) and B (n =36) group.Patients in group A were given metformin plus sitagliptin scheme for 12 weeks,and in group B were given metformin plus pioglitazone scheme for 12 weeks.The blood glucose level was measured and clinical efficacy and adverse drug reactions during treatment were record.Results (1) Fasting plasma glucose (FPG),2 h postprandial blood glucose(2 hPBG) and glycosylated hemoglobin(GH) in A and B group after 12 weeks of treatment were (6.4 ± 1.8) mmol/L,(7.0 ± 1.9) mmol/L; (8.1 ± 2.7) mmol/L,(9.5 ± 2.8) mmol/L; (6.2 ± 2.1) ％,(7.1 ± 2.2) ％,lower than that of pre-treatment ((9.4 ± 2.4) mmol/L,(9.1 ± 2.5) mmol/L; (13.6 ± 4.5) mmol/L,(13.3 ± 4.9) mmol/L; (9.2 ± 2.4) ％,(8.9 ± 2.6) ％ and the difference were significant (t =6.325,4.013,6.628,4.040,5.950,3.171 respectively,P ＜ 0.05).2 hPBG level of group A was (8.1 ±2.7) mmol/L,lower than that of group B ((9.5 ±2.8) mmol/L,t =2.214,P =0.030).(2) Efficiency in group A was 90.0％ (36/40),slightly higher than that of group B (83.3％ (30/36)),but the difference was not statistically significance (x2 =0.269,P =0.604).(3) There were no seriously adverse drug reactions in two groups.Rates of adverse reactions in two groups were 25.0％ (10 cases),30.6％ (11 cases) respectively (x2 =0.292,P =0.589).Conclusion Both treatment plans were proved effective in treatment of patients with T2DM.Compared with plan of metformin plus pioglitazone,metformin plus sitagliptin was showed a comparative advantage in clinical efficacy,especially with outstanding curative effect in reducing postprandial blood glucose.