Objective We performed a multicenter randomized trial to compare the long term effects of early short-term intensive diabetes treatment modalities. Methods Newly diagnosed, drug naive 97 type 2 diabetes mellitus (T2DM) patients were randomized to intensive insulin treatment (IIT, n = 50, multiple insulin treatment with glargine and glulisine) or combined oral antidiabetic agent (COAD, n = 47, glimepiride and metformin) group for early intensive treatment. Intensive treatment was performed in outpatient clinic and was finished after achieving A1c< 7% or total insulin requirement < 10 U/day or 12 weeks of duration. Patients were then followed-up for 104 weeks on diet/exercise alone or rescue drug therapy as a protocol. Primary endpoint was long term glycemic control and remission (A1c < 7% without medication) rate at 2 year after intensive therapy. Results After intensive treatment, both intervention groups could achieve successful glycemic control status within 12 weeks. However, mean intensive treatment period was significantly shorter in the IIT group (P < 0.001). During 104 weeks of follow-up period, both groups could maintain favorable glycemic control. However, mean A1c was significantly lower (P = 0.030), and proportion of subjects with A1c < 7% was higher in the IIT group during the follow-up period. Remission rate at 104 weeks was also significantly higher in the IIT groups (45.7% in IIT vs. 17.6% in COAD, P = 0.019). Conclusion Early intensive treatments with IIT or COAD in newly diagnosed T2DM patients were both effective on long glycemic control, but IIT was more favorable on the remission rate and maintenance of optimal glycemic control (NCT00474838).