Association of estimated plasma volume and weight loss after long‐term administration and subsequent discontinuation of the sodium‐glucose cotransporter‐2 inhibitor tofogliflozin

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2) are drugs that have been reported to have several effects through the regulation of plasma volume, for example, antihypertensive effects. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2 inhibitor tofogliflozin on estimated plasma volume (ePV), brain natriuretic peptide (BNP) and the relationship between changes in ePV, BNP and body weight (BW). Data from 157 participants with type 2 diabetes receiving tofogliflozin monotherapy in a phase 3 study were analysed.Changes in variables or correlations among them during a 52-week administration and a 2-week post-treatment period were investigated. Percent change in ePV was calculated using the Strauss formula. Significant decreases in BW, ePV and ln-transformed BNP (ln-BNP) were noted by week 52. %ΔBW was not significantly correlated with %ΔePV and Δln-BNP, while %ΔePV was significantly correlated with Δln-BNP. Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased. %ΔBW was significantly correlated with %ΔePV and Δln-BNP. Furthermore, ePV and BNP were significantly higher than baseline levels.

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.…”

Effects of long-term use of sodium-glucose co-transporter-2 inhibitors on plasma volume status in patients with type 2 diabetes mellitus: Sub-analysis of a prospective, observational study during the COVID-19 pandemic

“…Rapid attenuation of PV at 12 weeks has been shown with canagliflozin in patients with T2DM [11]. Finally, in the longest available study, long-term monotherapy with tofogliflozin in patients with T2DM produced a significant decrease in estimated PV 52 weeks post-initiation of treatment, however, that effect was rapidly ameliorated [12].…”

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

“… 12 Previous studies have reported that SGLT2 inhibitors reduced both the plasma volume measured by 125 I‐labelled human serum albumin and ePV by using laboratory data in patients with T2DM. 18 , 19 Other studies have also reported that SGLT2 inhibitors reduced the ePV in patients with T2DM complicated by cardiovascular diseases or HFrEF. 20 , 21 In addition, SGLT2 inhibitors reduced pulmonary arterial pressure in patients with heart failure.…”

“…Sodium glucose co‐transporter 2 inhibitors have some favourable effects on heart failure beyond their glucose‐lowering effects 12 . Previous studies have reported that SGLT2 inhibitors reduced both the plasma volume measured by 125 I‐labelled human serum albumin and ePV by using laboratory data in patients with T2DM 18,19 . Other studies have also reported that SGLT2 inhibitors reduced the ePV in patients with T2DM complicated by cardiovascular diseases or HFrEF 20,21 .…”

“… 16 , 17 Recently, SGLT2 inhibitors have been reported to reduce estimated plasma volume (ePV). 18 , 19 , 20 , 21 Although these results suggest that SGLT2 inhibitors may be effective in reducing intravascular volume, which may improve heart failure prognosis, there is little evidence of the efficacy of SGLT2 inhibitors on intravascular volume in patients with HFpEF.…”