Objective: Initial dual combination therapy of oral hypoglycemic agents showed good glycemic control compared to monotherapy. But there was no study using triple agents as initial combination, which is expected to show strong efficacy in glycemic control through potentially complementary mechanisms. The present study investigated the efficacy and safety of initial triple combination of metformin, sitagliptin, and lobeglitazone in patients with recently diagnosed type 2 diabetes. Methods: Seventy-eight patients aged 20 to 80 years with HbA1c level between 9.0-12.0% at diagnosis and no severe hyperglycemic symptoms were included. Metformin 500-2000mg/day, sitagliptin 100mg/day, and lobeglitazone 0.5mg/day were given to all patients for 12 months. Primary outcome was change of HbA1c level after treatment. Secondary outcomes were changes of β-cell function, insulin resistance, and lipid profiles. Body weight and body composition changes were assessed. We also assessed the percentage of receiving rescue therapy and adverse events. Results: The HbA1c levels decreased from 11.1 ± 1.7 to 7.2 ± 1.6% for 12 months. Among 78 patients, 58 (74.4%) were successfully maintained glycemic control (< 7.0% of HbA1c) for 12 months. In these patients, mean HbA1c level was significantly decreased from 11.1 ± 1.7 to 6.8 ± 1.3% (P < 0.001). The fasting plasma glucose showed significant decrease (233.3 ± 82.2 to 126.8 ± 38.7 mg/dL, P < 0.001) in treatment success group, and there were also significant changes in HOMA-β (27.5 ± 21.6 to 88.7 ± 55.3, P < 0.001) and HOMA-IR (7.6 ± 5.7 to 3.2 ± 1.7, P = 0.002). In this study, 20 patients needed the rescue therapy (sulfonylurea or insulin) due to insufficient glycemic control. This treatment failure group had longer duration of diabetes and lower fasting insulin levels compared to the success group (8.5 ± 6.0 vs. 4.4 ± 7.8 years; 6.6 ± 2.9 vs. 10.7 ± 6.4 μIU/mL, respectively). Adverse event such as hypoglycemia was not reported during study period in triple combination therapy. Conclusion: The present study demonstrated that initial triple combination therapy with metformin, sitagliptin, and lobeglitazone in drug-naïve patients with type 2 diabetes was effective and safe. Longer studies with large scale are needed to validate these results.