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 withempagliflozin, 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.
RCT Entities:
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.
Authors: Bernard Zinman; Christoph Wanner; John M Lachin; David Fitchett; Erich Bluhmki; Stefan Hantel; Michaela Mattheus; Theresa Devins; Odd Erik Johansen; Hans J Woerle; Uli C Broedl; Silvio E Inzucchi Journal: N Engl J Med Date: 2015-09-17 Impact factor: 91.245
Authors: Joseph G Verbalis; Steven R Goldsmith; Arthur Greenberg; Cynthia Korzelius; Robert W Schrier; Richard H Sterns; Christopher J Thompson Journal: Am J Med Date: 2013-10 Impact factor: 4.965
Authors: Helbert Rondon-Berrios; Srijan Tandukar; Maria K Mor; Evan C Ray; Filitsa H Bender; Thomas R Kleyman; Steven D Weisbord Journal: Clin J Am Soc Nephrol Date: 2018-09-04 Impact factor: 8.237
Authors: Joseph G Verbalis; Arthur Greenberg; Volker Burst; Jean-Philippe Haymann; Gudmundur Johannsson; Alessandro Peri; Esteban Poch; Joseph A Chiodo; Jiten Dave Journal: Am J Med Date: 2015-11-14 Impact factor: 4.965
Authors: Arthur Greenberg; Joseph G Verbalis; Alpesh N Amin; Volker R Burst; Joseph A Chiodo; Jun R Chiong; Joseph F Dasta; Keith E Friend; Paul J Hauptman; Alessandro Peri; Samuel H Sigal Journal: Kidney Int Date: 2015-02-11 Impact factor: 10.612
Authors: Julie Martin-Grace; Maria Tomkins; Michael W O'Reilly; Chris J Thompson; Mark Sherlock Journal: J Clin Endocrinol Metab Date: 2022-07-14 Impact factor: 6.134
Authors: Jenny Hui Ling Chieng; Tze Kai Sia; Yao Hao Teo; Joseph Zi An Wong; Tricia Jing Ying Ng; Yao Neng Teo; Nicholas L X Syn; Robin Cherian; Yoke-Ching Lim; Ping Chai; Weiqin Lin; Raymond C C Wong; Ching-Hui Sia Journal: Med Princ Pract Date: 2022-04-04 Impact factor: 2.132