DPP-4i do not increase weight and SGLT2i are expected to reduce weight; thus, are widely used in daily practice. SGLT2i are recommended as second-line drugs after metformin (Met) in those at high risk of atherosclerotic cardiovascular disease (ASCVD), but suitable second-line drugs for the majority of patients not at high risk are not yet determined. Furthermore, reports of appropriate second-line drugs in East Asians who have a lower risk of ASCVD than Europeans are scarce. We compared the effects of ipraglifrozin (Ipra) and sitagliptin (Sita) after Japanese patients with type 2 diabetes had been taking Met and were without prior ASCVD in a 52-week randomized open-label trial (jRCTs031180205). The primary endpoint (PE) was a HbA1c reduction of ≥0.5% with no weight gain at 52 weeks. Among 111 patients (mean age 59.2 y, mean BMI 26.6 kg/m2, and male 61.3%), 54 and 57 patients received Ipra and Sita, respectively. After 52 weeks, achievement of the PE was statistically the same (37.0% and 40.3%, p=0.72), as was the HbA1c reduction ≥0.5% (38.9% and 54.4%, p=0.13). Lack of weight gain was higher for Ipra than Sita (94.4% and 54.4%, p<0.01). BMI, C-peptide and HDL-C improved with Ipra vs. Sita (p<0.05). Withdrawal for any adverse event occurred in 8 with Ipra and 4 with Sita (14.8% and 7.0%, p=0.23).Although glycemic control did not differ between Ipra and Sita, some ASCVD risk factors improved with Ipra. Disclosure M. Kitazawa: None. T. Katagiri: None. H. Suzuki: None. S. Matsunaga: None. M.H. Yamada: None. T. Ikarashi: None. M. Yamamoto: None. K. Furukawa: None. M. Iwanaga: None. M. Hatta: None. K. Fujihara: None. T. Yamada: None. S. Tanaka: None. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Funding Astellas Pharma Inc.