BACKGROUND Treatment options to address the hyponatremia induced by the syndrome of inappropriate antidiuresis (SIAD) are inadequate. The sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion and therefore, might offer a novel treatment option for SIAD. METHODS In this double-blind, randomized trial, we recruited 88 hospitalized patients with SIAD-induced hyponatremia <130 mmol/L at the University Hospital Basel from September 2016 until January 2019 and assigned patients to receive, in addition to standard fluid restriction of <1000 ml/24 h, a once-daily dose of oral empagliflozin or placebo for 4 days. The primary end point was the absolute change in plasma sodium concentration after 4 days of treatment. Secondary end points included predisposing factors for treatment response and safety of the intervention. RESULTS Of the 87 patients who completed the trial, 43 (49%) received treatment with empagliflozin, and 44 (51%) received placebo. Baseline plasma sodium concentrations were similar for the two groups (median 125.5 mmol/L for the empaflozin group and median 126 mmol/L for the placebo group). Patients treated with empagliflozin had a significantly higher increase of median plasma sodium concentration compared with those receiving placebo (10 versus 7 mmol/L, respectively; P=0.04). Profound hyponatremia (<125 mmol/L) and lower baseline osmolality levels increased the likelihood of response to treatment with empagliflozin. Treatment was well tolerated, and no events of hypoglycemia or hypotension occurred among those receiving empagliflozin. CONCLUSIONS Among hospitalized patients with SIAD treated with fluid restriction, those who received empagliflozin had a larger increase in plasma sodium levels compared with those who received placebo. This finding indicates that empagliflozin warrants further study as a treatment for the disorder.

中文翻译：

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恩帕格列净增加抗利尿不当综合征患者血浆钠水平的随机试验。

背景技术解决由不适当抗利尿综合征（SIAD）引起的低钠血症的治疗选择是不足的。钠葡萄糖共转运蛋白2（SGLT2）抑制剂依帕格列净通过尿葡萄糖排泄促进渗透性利尿，因此，可能为SIAD提供新的治疗选择。方法在这项双盲，随机试验中，我们从2016年9月至2019年1月在巴塞尔大学医院招募了88名SIAD引起的低钠血症<130 mmol / L的住院患者，除标准体液限制为< 1000毫升/ 24小时，每天一次口服口服恩帕格列净或安慰剂，持续4天。主要终点是治疗4天后血浆钠浓度的绝对变化。次要终点包括治疗反应和干预安全性的诱发因素。结果在完成试验的87位患者中，有43位（49％）接受了依帕格列净治疗，而44位（51％）接受了安慰剂。两组的基线血浆钠浓度相似（安非氟嗪组中位数为125.5 mmol / L，安慰剂组中位数为126 mmol / L）。与接受安慰剂的患者相比，接受依帕格列净治疗的患者的血浆钠中位数增加明显（分别为10和7 mmol / L； P = 0.04）。严重的低钠血症（<125 mmol / L）和较低的基础摩尔渗透压浓度增加了依帕格列净治疗反应的可能性。治疗耐受良好，接受恩帕格列净的患者未发生低血糖或低血压事件。结论在接受液体限制治疗的SIAD住院患者中，与接受安慰剂的患者相比，接受依帕格列净治疗的患者血浆钠水平的升高幅度更大。这一发现表明，依帕格列净值得进一步研究以治疗该疾病。