Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction

Abstract

Aims Sodium glucose co‐transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). Methods and results This study was a post‐hoc analysis of the MUSCAT‐HF trial (UMIN000018395), a multicentre, prospective, open‐label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed‐effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group‐difference −6.43% [95% confidence interval (CI): −9.11 to −3.74]}, at Week 12 [−8.73% (95%CI: −11.40 to −6.05)], and at Week 24 [−11.02% (95%CI: −13.71 to −8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log‐transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). Conclusions Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

“…On the basis of a comprehensive review, we identified 15 studies that evaluated the effect of SGLT2 inhibitors on plasma volume (Table 2). 64,[72][73][74]78,[98][99][100][101][102][103][104][105][106][107][108][109] Unfortunately, most studies estimated changes in plasma volume using the Kaplan-Hakim and Strauss formulae, which cannot be applied to the evaluation of changes produced by SGLT2 inhibitors. Four reports 64,72,74,109 used indicator dilution methods, and of these, 3 were double blind and placebo controlled.…”

Association between Cardiovascular Disease and Liver Disease, from a Clinically Pragmatic Perspective as a Cardiologist

“…Sodium-glucose co-transporter-2 inhibitors have some benefits beyond their glucose-lowering effects, such as promoting natriuresis and osmotic diuresis based on glycosuria. These effects advantageously affect patients with HF as they decrease cardiac preload and improve prognosis [ 69 , 70 , 71 , 72 , 73 , 74 ]. Thus, current guidelines for the management of HF recommend the use of sodium-glucose co-transporter-2 inhibitors for patients with both HF with reduced ejection fraction and HF with preserved ejection fraction regardless of the presence of diabetes mellitus [ 44 ].…”

“…Liver stiffness measured with shear wave elastography has been used to evaluate liver fibrosis non-invasively [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. A shear wave is generated by inducing a push pulse of an ultrasound wave, which deforms a part of the tissue.…”