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Highlights • Small dense LDL-C (sd LDL-C) convey cardiovascular risk in type 2 diabetes (T2D). • Ipragliflozin reduced sd LDL-C levels in Japanese patients with T2D. • Changes in body weight, TG and LDL-C levels contributed to sd LDL-C reduction., Aims This preliminary randomized, parallel-group comparative study evaluated the efficacy of ipragliflozin for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). Methods Sixty-two patients with T2DM (age, 56 ± 8 years; hemoglobin A1c levels, 8.1 ± 0.9%; BMI, 27.5 ± 3.3 kg/m2) were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day) (treatment group; n = 40) or continued treatment (control group; n = 22) for 12 weeks. The primary endpoints were changes in sd LDL-C levels detected using the LipoPhor AS® system; the secondary endpoints included changes in the sd LDL-C/large buoyant LDL-C (lb LDL-C) ratio, a surrogate marker for LDL particle size, and percent changes in routine lipid parameters. Results The treatment group exhibited a statistically significant reduction from baseline for LDL-C levels (−0.37 mg/dL vs. 14.4 mg/dL, p = 0.038), sd LDL-C levels (−1.28 mg/dL vs. 2.81 mg/dL, p = 0.012), and sd LDL-C/lb LDL-C ratio (−3.20% vs. 4.58%, p = 0.040) compared with the control group. Multiple regression analysis among all subjects revealed change in TG levels (p = 0.011) and LDL-C levels (p = 0.024) as well as change in body weight (p = 0.006) as independent factors contributing to the reduction in sd LDL-C. Conclusions Ipragliflozin may have a potential for lowering sd LDL-C levels associated with increasing LDL particle size in Japanese patients with T2DM.