Effects of the SGLT2-inhibitor Empagliflozin on Patients With SIADH - the SAND Study (SAND)

Syndrome of inappropriate antidiuresis (SIADH) is characterized by an imbalance of antidiuretic vasopressin (AVP) secretion. The impaired AVP regulation leads to water retention and secondary natriuresis and is a common cause for hyponatremia. The therapeutic options, aside from treating the underlying disease, depend upon the onset and severity of the symptoms and involve usually fluid restriction or hypertonic saline infusion. Alternative therapeutic options are loop diuretics, administration of oral urea or vasopressin receptor antagonists (vaptans). Despite those options, there are a considerable number of patients which do not sufficiently respond, making additional therapy necessary. Empagliflozin (Jardiance)® is a sodium glucose co-transporter 2 (SGLT2)-inhibitor, which is a new treatment option developed for patients with diabetes mellitus type 2. The SGLT2 is expressed in the proximal tubule and reabsorbs approximately 90 percent of the filtered glucose. The inhibition of SGLT2 results in renal excretion of glucose with subsequent osmotic diuresis. This mechanism could result in a therapeutic effect in patients with hypotonic hyponatremia as in SIADH. The aim of this study is to evaluate whether empagliflozin (Jardiance)® has an effect on the serum sodium levels of patients with SIADH.

The primary outcome is the change in serum sodium concentration from baseline to day 5, i.e. 4 days after start of treatment with study drug

Inclusion Criteria: - Hyponatremia <130mmol/l due to SIADH Exclusion Criteria: any Treatment for SIADH during >48h before study start severe illness with ICU-Admission Treatment with 3% sodium Chloride (NaCl) solution uncontrolled hypothyroidism uncontrolled adrenal insufficiency severe renal impairment (GFR <30ml/min), end stage renal disease severe hepatic impairment (Child-Pugh class C) systolic blood pressure <90mmHg Diabetes mellitus type 1 acute myocardial infarction or chronic venous insufficiency (CVI) Treatment with SGLT2 Inhibitor, Lithium Chloride or Urea recurrent urinary-/genital tract infections contraindication for lowering blood pressure severe immunosuppression pregnancy or breastfeeding palliative care

Nobbenhuis R, Refardt J, Vogt D, Sailer CO, Winzeler B, Christ-Crain M. Can treatment response to SGLT2-inhibitors in syndrome of inappropriate antidiuresis be predicted by copeptin, natriuretic peptides and inflammatory markers? Biomarkers. 2021 Nov;26(7):647-655. doi: 10.1080/1354750X.2021.1970808. Epub 2021 Aug 30.