OBJECTIVES: To evaluate the efficacy and safety of therapeutic alternatives provided in the SUS, in monotherapy and combinations for the treatment of T2DM.   METHODS: Systematic review (SR) with meta-analysis of randomized controlled trials (RCTs) available in PubMed, LILACS, CENTRAL databases (October/2014), including manual and gray literature search. Meta-analysis was conducted in Review Manager®5.2 software by applying the random effects model. The primary outcomes were, concentration(%) of glycated hemoglobin (GHb), blood or plasma glucose concentrations and occurrence of adverse events. Methodological quality was assessed using the modified Jadad scale and Risk of bias according to the recommendations of the Cochrane Collaboration. RESULTS: There were included 33 RCT´s of the 9,715 achieved publications: 4 compared NPH Insulin + Regular Insulin (RI) vs. Glibenclamide, 1 (NPH + RI vs. NPH + Glibenclamide), 6 (NPH + IR vs. NPH + RI + metformin), 2 (NPH + RI + Glibenclamide vs. Glibenclamide + Metformin), 1 (NPH + Glibenclamide vs. RI + Glibenclamide), 1(Metformin vs. Gliclazide), 10 (Glibenclamide vs. Metformin ) 1(Metformin vs. Metformin + gliclazide), 7 (Metformin vs Metformin + Glibenclamide), 10 (Glibenclamide vs Glibenclamide + Metformin) 3 (Glibenclamide vs. Gliclazide) and 1(Gliclazide vs. Glibenclamide + Metformin). The evidence points to satisfactory efficacy and safety profiles of the drugs available on SUS for the treatment of T2DM. Insulin preparations have greater GHb reduction capability, but a higher incidence of hypoclycemic episodes than oral antidiabetic agents, which have similar profile of efficacy and safety. Combination therapy followed a similar pattern. Studies on direct comparison between drugs support no sufficient evidence to rank then.  CONCLUSIONS: Considering the efficacy and safety of medicines supplied by SUS, the choice of T2DM therapy depends on the stage of the disease and on patient's preferences. Insulin preparations should preferably be introduced to patients at more advanced stages of the disease.