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<p>We previously demonstrated that combining a sodium–glucose cotransporter 2 (SGLT2) inhibitor with diuretics significantly reduces interstitial fluid volume without excessive depletion of circulating plasma volume or activation of the renin–angiotensin–aldosterone system (RAAS). However, the differential effects of SGLT2 inhibitor monotherapy versus combination therapy with diuretics on fluid dynamics in patients with pre-existing fluid retention remain unclear. This study included patients with fluid retention, defined by an extracellular water to total body water (ECW/TBW) ratio &gt; 0.400, as measured by bioimpedance analysis. We evaluated 6-month changes in body fluid status and serum copeptin levels, a surrogate marker for vasopressin, between two groups: patients receiving SGLT2 inhibitor dapagliflozin monotherapy (SGLT2i group, n = 13; estimated glomerular filtration rate [eGFR] 25.0 ± 8.5 mL/min/1.73 m<sup>2</sup>) and those receiving dapagliflozin in combination with loop or thiazide diuretics (SGLT2i + diuretic group, n = 18; eGFR 29.8 ± 15.2 mL/min/1.73 m<sup>2</sup>). Changes in systolic blood pressure and estimated plasma volume did not significantly differ between groups. However, reductions in ECW/TBW, TBW, and interstitial fluid were significantly greater in the combination group than in the monotherapy group. Moreover, the increase in serum copeptin was significantly suppressed in the SGLT2i + diuretic group. No significant intergroup differences were observed in renin and aldosterone changes. These findings suggest that co-administration of SGLT2 inhibitor with diuretics can more effectively reduce interstitial fluid retention without inducing excessive plasma volume reduction or RAAS activation.</p><p></p>

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SGLT2 inhibitor requires co-administration with diuretics to effectively reduce interstitial fluid retention: the DAPA-BODY trial

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • Takahiro Masuda,
  • Maki Asakura-Kinoshita,
  • Kentaro Oka,
  • Ken Ohara,
  • Masato Sakai,
  • Marina Miura,
  • Kyohei Misawa,
  • Keiji Hirai,
  • Masato Morinari,
  • Tetsu Akimoto,
  • Kazuyuki Shimada,
  • Daisuke Nagata,
  • Yoshiyuki Morishita

摘要

We previously demonstrated that combining a sodium–glucose cotransporter 2 (SGLT2) inhibitor with diuretics significantly reduces interstitial fluid volume without excessive depletion of circulating plasma volume or activation of the renin–angiotensin–aldosterone system (RAAS). However, the differential effects of SGLT2 inhibitor monotherapy versus combination therapy with diuretics on fluid dynamics in patients with pre-existing fluid retention remain unclear. This study included patients with fluid retention, defined by an extracellular water to total body water (ECW/TBW) ratio > 0.400, as measured by bioimpedance analysis. We evaluated 6-month changes in body fluid status and serum copeptin levels, a surrogate marker for vasopressin, between two groups: patients receiving SGLT2 inhibitor dapagliflozin monotherapy (SGLT2i group, n = 13; estimated glomerular filtration rate [eGFR] 25.0 ± 8.5 mL/min/1.73 m2) and those receiving dapagliflozin in combination with loop or thiazide diuretics (SGLT2i + diuretic group, n = 18; eGFR 29.8 ± 15.2 mL/min/1.73 m2). Changes in systolic blood pressure and estimated plasma volume did not significantly differ between groups. However, reductions in ECW/TBW, TBW, and interstitial fluid were significantly greater in the combination group than in the monotherapy group. Moreover, the increase in serum copeptin was significantly suppressed in the SGLT2i + diuretic group. No significant intergroup differences were observed in renin and aldosterone changes. These findings suggest that co-administration of SGLT2 inhibitor with diuretics can more effectively reduce interstitial fluid retention without inducing excessive plasma volume reduction or RAAS activation.