5-OR: Cardioprotective Effect of Luseogliflozin in Patients with Type 2 Diabetes and Established Cardiovascular Disease

Abstract

Recent published CV outcome trials have revealed that sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduced the combined CV endpoint and incidences of heart failure-associated hospitalizations in patients with type 2 diabetes mellitus (T2DM) and CV disease (CVD). However, detailed mechanisms of the benefits by SGLT2i still remain unknown. Especially, nobody can show the consensus opinion in the mechanistic effects of SGLT2i on the left ventricular (LV) diastolic dysfunction associated with T2DM. We focused the spectral tissue Doppler-derived E/e' ratio, which has been validated in simple and reproducible noninvasive assessment of LV diastolic pressures independent of rhythm, and evaluated whether or not the treatment of SGLT2i, luseogliflozin, used for 6 months could affect cardiac function in 25 patients with T2DM and CVD. Luseogliflozin used for 6 months significantly reduced HbA1c levels (8.2 ± 1.2% to 7.4 ± 0.6%, p < 0.01) and systolic blood pressure (SBP)(125.6 ± 18.1 mmHg to 119.3 ± 16.8 mmHg, p = 0.04) compared to baseline levels. Moreover, luseogliflozin also significant reduced left atrial (LA) (42.2 ± 5.7 mm to 39.9 ± 6.8 mm, p = 0.01) and LV diameters (diastolic, 49.5 ± 6.9 mm to 47.6 ± 7.6 mm, p = 0.01; systolic, 35.8 ± 9.1 mm to 33.9 ± 9.8 mm, p < 0.01). Remarkably, early annular tissue Doppler (e’) velocity and peak early diastolic velocity/basal septal diastolic velocity (E/e’) ratio were significantly improved, and these benefits were augmented in the group of e’< 6.0cm/sec of baseline (e’ velocity, 4.8 ± 0.6 cm/sec to 5.8 ± 0.9 cm/sec, p < 0.01; E/e’ ratio, 13.0 ± 4.9 to 10.9 ± 3.4, p = 0.03, respectively). There was a significant negative correlation between the changes in E/e’ ratio and baseline of E/e.’ These results indicated that lusegliflozin improved hemodynamics associated with LV diastolic function in the patients with T2DM and CVD, and support the cardio-protective effects of SGLT2i of T2DM with CVD. Disclosure Y. Ina: None. T. Kishi: None. N. Sekiguchi: None. N. Sakane: Board Member; Spouse/Partner; Kao Corporation.