Treatment with empagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), increases plasma sodium levels in patients with hyponatremia caused by SIAD, according to findings of a study reported in the Journal of the American Society of Nephrology.¹

Eighty-seven adult patients with hyponatremia (<130 mmol/L [130 mEq/L]) due to SIAD admitted to a University Hospital in Switzerland from September 2016 to January 2019 were enrolled for this prospective, randomized, placebo-controlled trial. They were randomized to either oral empagliflozin (43/87;49%) once-a-day or placebo (44/87;51%) for 4 days. Additionally, all participants were subjected to standard fluid restriction to less than1000 ml in 24 hours. The objective of the study was to investigate the impact of empagliflozin on plasma sodium levels. The absolute change in plasma sodium levels from the time of study entry to day 4 was the primary end point.

Analysis of data showed that the median plasma sodium levels were comparable between the two groups at baseline; 125.5 mmol/L (125.5 mEq/L) in the empagliflozin-treated patients and 126 mmol/L (126 mEq/L) in those who received placebo. The rise in median plasma sodium was significantly greater following the 4-day treatment with empagliflozin (10 mmol/L) than with placebo (7 mmol/L). Response to empagliflozin was more likely in patients with sodium levels less than 125 mmol/L (125 mEq/L) and lower osmolality levels at baseline. Patients tolerated empagliflozin well without occurrence of hypotension or hypoglycemia. However, the researchers have cautioned about the occurrence of prerenal stress due to the “combination of fluid restriction and increased excretion of free water” causing transient renal dysfunction with empagliflozin. This must particularly be taken into consideration when managing elderly patients.

The management of hyponatremia due to syndrome of inappropriate antidiuresis (SIAD) is wrought with several challenges. Fluid restriction, the standard treatment, may not always be of help. Compliance to drugs like the vaptans (vasopressin receptor antagonists) is poor due to their high costs and the risk of rapid overcorrection.  There is therefore a need for a safe and effective treatment option for SIAD.  This trial is the first to show the increase in plasma sodium levels with empagliflozin in these patients compared to placebo suggesting empagliflozin as a potential new therapeutic option for the treatment of hyponatremia due to SIAD besides fluid restriction.

Reference

1. Julie Refardt, et al. A randomized trial of empagliflozin to increase plasma sodium levels in patients with the syndrome of inappropriate antidiuresis. J Am Soc Nephrol. 2020 Mar;31(3):615-624. doi: 10.1681/ASN.2019090944.