我们先前报道过,钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂通过代偿性增加渗透性利尿诱导的加压素分泌和液体摄入而发挥持续的液体稳态作用。然而,单独的SGLT2抑制剂不能产生流体潴留的持久改善。在这项研究中,我们检查了SGLT2抑制剂达格列净(SGLT2i组,n=53)以及达格列净和常规利尿剂的联合使用,包括loop利尿剂和/或噻嗪类(SGLT2i利尿剂组,n=23),血清和肽素,一个稳定的,敏感,和血管加压素释放和体液状态的简单替代标记。经过6个月的治疗,SGLT2i利尿剂组的和肽素变化明显低于SGLT2i组(-1.4±31.5%vs.31.5±56.3%,p=0.0153)。使用Strauss公式计算的估计血浆体积的变化在两组之间没有显着差异。相反,间质液的变化,细胞外水,细胞内水,SGLT2i+利尿剂组的总水量明显低于SGLT2i组。肾素的变化,醛固酮,和绝对肾上腺素水平在两组之间没有显着差异。总之,SGLT2抑制剂dapagliflozin和常规利尿剂的联合使用抑制了和肽素水平的升高,并显著改善了液体潴留,而不会过度减少血浆容量和激活肾素-血管紧张素-醛固酮和交感神经系统.
We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.