Object: We aimed to determine clinical variables associated with better glucose lowering response to sodium glucose co-transporter 2 (SGLT2) inhibitor, ipragliflozin, treatment in patients with type 2 diabetes with an interest on urinary glucose excretion (UGE). Methods: This was a single-arm multicenter prospective study. A total of 92 patients with type 2 diabetes aged 20 to 70 years and HbA1c levels ≥ 7.0% and ≤ 9.5% were enrolled and ipragliflozin 50 mg was added to background therapy during 12 weeks. Changes in HbA1c and morning spot urine or 8h overnight UGE were measured before and after treatment. Results: Mean age was 56.5 years and median duration of diabetes was 6 years. After 3 months treatment with ipragliflozin, mean HbA1c levels were decreased from 7.6% to 6.9% and 62.0% of patients reached HbA1c target of less than 7.0% (P < 0.001). In addition, body weight, blood pressure, and lipid parameters were improved after the treatment (all P < 0.001). Baseline HbA1c (r = 0.66, P < 0.001) and morning spot urine glucose to creatinine ratio (r = -0.30, P = 0.001) were independently associated with the reduction of HbA1c. However, the reduction of HbA1c did not show any correlation with changes in clinical and biochemical variables including change in UGE after ipragliflozin treatment. Overall, ipragliflozin treatment was well tolerated and no hypoglycemic events were observed. Conclusion: Ipragliflozin treatment for 12 weeks improved glycemic control and other metabolic parameters. A higher HbA1c and lower UGE at baseline predicted better glucose lowering efficacy in patients with type 2 diabetes.