1835-P: Effect of Luseogliflozin on Myocardial Flow Reserve in Patients with Type 2 Diabetes Mellitus (LUCENT-J Study)

Introduction and Objective: Sodium-glucose cotransporter2 (SGLT2) inhibitors reduce hospital admission rates for heart failure (HF) in patients with type 2 diabetes (T2DM). However, the mechanisms of cardioprotection of SGLT2 inhibitors are not fully understood. Despite advances in the treatment of coronary artery disease (CAD), the prevalence of HF continues to increase among patients with T2DM. Preclinical studies suggest that SGLT2 inhibitors may improve vascular endothelial function through multiple molecular pathways, thereby contributing to the amelioration of impaired myocardial microcirculation commonly observed in diabetes. This study investigated the effects of SGLT2 inhibitors on cardiac microcirculation in patients with T2DM. 13N-ammonia positron emission tomography (PET) studies can be used to assess coronary microvascular dysfunction non-invasively. This study aimed to elucidate the effects of SGLT2 inhibitors on cardiac microcirculation as measured by myocardial flow reserve (MFR) using 13N-ammonia PET. Methods: This study was a prospective, single-center, randomized, parallel-group open-label, active-controlled study including 40 patients. Registration was set with a target HbA1c <8% to minimize the impact on glycemic control, and patients with CAD requiring coronary revascularization or suspected CAD requiring coronary angiography were excluded. The primary outcome was the detection of changes in MFR at week 24. Results: 33 participants met the per-protocol criteria, 17 in the luseogliflozin group and 16 in the control group. Participants were men (55%), with mean (SD) Age of 72.9y (±9.6), HbA1c of 6.9% (±0.9). There was no significant change in MFR in the luseogliflozin group (2.26 ± 0.38 vs 2.35 ± 0.55 p = 0.464 compared with the placebo group 2.25 ± 0.44 vs 2.28 ± 0.51 p = 0.869; Pint= 0.699). Luseogliflozin significantly improved LVEF (72.7 ± 4.9 vs 75.7 ± 4.6 p = 0.033 compared with the placebo group 75.0 ± 5.9 vs 74.6 ± 6.5 p = 0.573; Pint= 0.041). Conclusion: This study showed that MFR didn’t increase by luseogliflozin. Disclosure T. Tamanaha: None. C. Son: Speaker's Bureau; Current; Eli Lilly and Company. Speaker's Bureau; Ended; Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Novo Nordisk, AstraZeneca, Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd. R. Koezuka: None. M. Tochiya: Research Support; Current; SARAYA.co, Sumitomo Dainippon Pharma Co., Ltd. Y. Omura-Ohata: None. K. Kohmo: None. M. Noguchi: None. H. Makino: None. Funding Taisho Pharmaceutical Co., Ltd. Funded this study