Effects of Tofogliflozin on Cardiac Function in Elderly Patients With Diabetes Mellitus

Abstract

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction (EF). Recent clinical data suggest that several sodium glucose transporter-2 (SGLT2) inhibitors are found to reduce cardiovascular disease (CVD) events in elderly diabetic patients, but the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD is unknown. We retrospectively investigated the effect of tofogliflozin on cardiac function in elderly patients with T2DM. Methods: Patients received 20 mg of tofogliflozin daily for 1 month. EF, ratio of early filling to atrial filling (E/A), a change in mitral inflow E and mitral e' annular velocities (E/e'), left atrial dimension (LAD) and maximal diameter of inferior vena cava (IVC max) were measured between baseline and 1 month after the administration of tofogliflozin. Results: Body weight, systolic and diastolic blood pressures significantly decreased, while renin and aldosterone level significantly increased after 1 month of tofogliflozin treatment. Most of the physiological parameters and the level of serum electrolyte did not change significantly. E/A, E/e' and LAD significantly decreased, while no significant changes were observed in EF and IVC max. The interactions of E/e' between time, gender and age were not significant. Conclusion: The present study suggested that tofogliflozin improved left ventricular diastolic function irrespective of gender and age, while preserving IVC, renal function and electrolyte balance.

Gender Differences in Cardiac Function Following Three-Month Administration of Tofogliflozin in Patients With Diabetes Mellitus

“…The present study found that LV diastolic function as measured by E/e' for patients with T2DM had significantly improved 3 months after administration of tofogliflozin in elderly patients with T2DM, consistent with the previous results [ 14 - 16 ]. Other cardiac functional parameters such as diameter of LAD and IVCmax did not change 3 months after administration of tofogliflozin.…”

“…The present study found that LV diastolic function as measured by E/e' for patients with T2DM had significantly improved 3 months after administration of tofogliflozin in elderly patients with T2DM, consistent with the previous results [14][15][16].…”

“…Tofogliflozin was found to improve LV dilatation and vascular endothelial function in Japanese patients with T2DM, presumably via elevation of ketone bodies induced by tofogliflozin which might contribute to a protective effect in LV diastolic dysfunction [14,15]. Recently, our study suggested that there were gender differences in the effect of tofogliflozin in Japanese elderly patients with T2DM using mixed effect model [16]. However, little is known concerning the gender difference of the effect, especially in elderly people.…”

Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study

“…SGLT2 inhibitor-induced plasma volume reduction and hemoconcentration leading to improvement of oxygen transport could contribute to the efficient myocardial energetics. Indeed, SGLT2 inhibitors including tofogliflozin significantly improve left ventricular diastolic function in patients with T2DM [45,47]. It remains unclear whether there are differences in cardiac effects between agents belonging to this class of drugs, while a clinical comparison of tofogliflozin and empagliflozin based on a 48-week retrospective analysis showed that empagliflozin had a significantly stronger effect on the hematocrit than tofogliflozin [48].…”

Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study 

“…In this study the improvement in diastolic function was independent of E, but attributable to reduced early diastolic left ventricular relaxation and paralleled by a reduction in LVMI 22 . Furthermore Higashikawa et al reported Tofogli ozin to improve E/e' in 42 elderly patients with diabetes 23 .…”