Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland;
Department of Clinical Research, University of Basel, Basel, Switzerland; and.
J Am Soc Nephrol. 2020 Mar;31(3):615-624. doi: 10.1681/ASN.2019090944. Epub 2020 Feb 4.
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 urinary glucose excretion and therefore, might offer a novel treatment option for SIAD.
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.
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; =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.
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.
针对抗利尿激素不适当分泌综合征（SIAD）引起的低钠血症，治疗选择有限。钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂恩格列净可促进渗透性利尿和尿糖排泄，因此可能为 SIAD 提供一种新的治疗选择。
在这项双盲、随机试验中，我们于 2016 年 9 月至 2019 年 1 月在巴塞尔大学医院招募了 88 名因 SIAD 导致的血钠<130mmol/L 的住院患者，并将患者分为接受标准液体限制（<1000ml/24h）加每日一次口服恩格列净或安慰剂治疗 4 天的两组。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的易患因素和干预措施的安全性。
87 名完成试验的患者中，43 名（49%）接受恩格列净治疗，44 名（51%）接受安慰剂治疗。两组患者的基线血浆钠浓度相似（恩格列净组中位数为 125.5mmol/L，安慰剂组中位数为 126mmol/L）。与接受安慰剂治疗的患者相比，接受恩格列净治疗的患者的血浆钠浓度中位数升高更显著（分别为 10 与 7mmol/L，P=0.04）。严重低钠血症（<125mmol/L）和较低的基线渗透压水平增加了对恩格列净治疗有反应的可能性。治疗耐受性良好，接受恩格列净治疗的患者未发生低血糖或低血压事件。
在接受液体限制治疗的 SIAD 住院患者中，与接受安慰剂治疗的患者相比，接受恩格列净治疗的患者血浆钠水平升高更显著。这一发现表明，恩格列净作为该疾病的治疗方法值得进一步研究。
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