BACKGROUND Teneligliptin is a novel, highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor. The aim of this study is to explore the glycemic and non-glycemic efficacies of teneligliptin as an initial therapy. METHODS Newly diagnosed, drug naive Japanese subjects with type 2 diabetes (T2DM) were assigned to 20 mg/day teneligliptin monotherapy (n = 31). At 3 months, levels of glycemic and other parameters were compared with those at baseline. RESULTS Significant reductions of HbA1c (from 10.34 ± 2.06 to 8.38 ± 2.23%) and fasting blood glucose (FGB, from 211.3 ± 68.4 to 167.3 ± 70.2 mg/dL) levels were observed without any clinically significant adverse events. However, significant increases of uric acids (UA) levels were observed and two subjects reported mild hypoglycemic events. Homeostasis model assessment-B (HOMA-B) levels significantly increased, while high HOMA-R levels significantly decreased. Significant correlations were observed between the changes (Δ) of HbA1c and those of HOMA-B, and between ΔFBG and ΔHOMA-R. No changes in lipid and body weight were noted. CONCLUSIONS Teneligliptin might be effectively and safely used as an initial therapy for newly diagnosed T2DM. Glycemic efficacy of teneligliptin is obtained through activating beta-cell function as well as decreasing insulin resistance.