Background: The efficacy and safety of SGLT-2 and DPP-4 inhibitor monotherapies in T2DM is well established; however, data on the effect of combination therapies and sequence of administration are lacking. We investigated the efficacy and safety of the sequence of SGLT-2 and DPP-4 inhibitor administration in Japanese T2DM patients.Research design and methods: In this single-institution, open-label, randomized controlled study, T2DM patients inadequately controlled (HbA1c ≥6.5%) with conventional therapy were randomized to receive luseogliflozin-sitagliptin (LS; luseogliflozin 2.5 mg for 0-12 weeks, then luseogliflozin plus sitagliptin 50 mg for 12-24 weeks) or sitagliptin-luseogliflozin (SL; sitagliptin 50 mg for 0-12 weeks, then sitagliptin plus luseogliflozin 2.5 mg for 12-24 weeks). The main outcome was the difference in mean change in HbA1c at 24 weeks relative to baseline between both groups.Results: Of the 41 enrolled and randomized patients, 34 completed the study. Mean ± SD HbA1c at baseline was 10.35 ± 1.04% and 10.02 ± 1.40% in the LS and SL groups, respectively, and mean ± SD change in HbA1c at 24 weeks from baseline was -3.81 ± 1.21% vs -2.46 ± 1.42% (P < 0.01), respectively. No drug-related adverse events were reported.Conclusion: Over the 24-week period, LS was more effective in reducing HbA1c levels than SL in Japanese T2DM patients.