SGLT2 inhibitors (SGLT2is) promote diuresis and reduce plasma volume (PV). However, the impact of long-term administration and subsequent withdrawal of SGLT2is on PV is little known. This study investigated the effect of long-term administration and then withdrawal of the SGLT2i, tofogliflozin (TOFO), on PV and explored correlations with variables in type 2 diabetes mellitus (T2DM).

Analyzed were 166 T2DM patients who received TOFO for 52 weeks as initial monotherapy and underwent 2 weeks of withdrawal (week 54) in a phase-3 study. Percent change in estimated PV (%ΔePV) was calculated by the Strauss formula: {100*(pre Hb/post Hb)*[(100 - pre Ht)/(100 - post Ht)] - 100}. Baseline characteristics were: male (66%), age (mean: 58 y), HbA1c (8%), BMI (26kg/m2), BNP (12pg/mL) and eGFR (84mL/min/1.73m2). Paired t-tests analyzed differences from baseline to week 52 and from week 52 to 54. Correlation analysis was performed by Pearson’s product-moment correlation coefficients. Multivariate analysis explored predictors for %ΔePV.

Body weight (BW) [mean, -3kg (-5%)*; * p<0.01 vs. baseline], ePV (-2.7%*) and ln-transformed BNP [ln-BNP: -0.1ln(pg/mL)*] had significantly decreased by week 52. %ΔBW was not significantly correlated with %ΔePV (r=-0.06) and Δln-BNP (r=0.13) while %ΔePV was significantly correlated with Δln-BNP (r=0.35). Higher baseline ln-BNP levels were independently correlated with greater reductions in %ΔePV. After 2 weeks of withdrawal, BW [+0.9kg (+1.3%)†, † p<0.001 vs. week 52], ePV (+6.5%†) and ln-BNP [+0.3ln(pg/mL) †] were significantly increased. %ΔBW was significantly correlated with %ΔePV (r=0.22) and Δln-BNP (r=0.32). Also, %ΔePV was significantly correlated with Δln-BNP (r=0.30).

After long-term TOFO therapy, reduced PV might be correlated not with weight loss but with reduced BNP indicating fluid loss and baseline BNP might predict changed PV. Weight gain after TOFO withdrawal might be caused by fluid gain.


Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Company, Ltd. T. Nojima: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. K. Fujihara: None. K. Kaku: Advisory Panel; Self; Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc. Consultant; Self; Sanwa Kagaku Kenkyusho. Research Support; Self; Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

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