Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study

Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study

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.

Especially chronic (>72h) SIADH is difficult to treat as standard therapeutic options (water restriction, urea, salt tablets) often do not succeed in correction of hyponatremia, making additional therapy necessary.

Empagliflozin is a sodium glucose co-transporter 2 (SGLT2)-inhibitor, which is a well-tolerated treatment option for type 2 diabetes mellitus. The inhibition of SGLT2 in the proximal tubule leads to renal excretion of glucose with subsequent osmotic diuresis. This mechanism could result in a therapeutic effect in patients with chronic SIADH, as it resembles the aquaretic effect of urea.

The aim of this study is to evaluate whether empagliflozin has an effect on the serum sodium levels of patients with chronic SIADH.

Inclusion Criteria:

Adult patients (age ≥ 18 years) with hyponatremia (<133mmol/l) due to chronic (>72h) SIADH defined as

• serum osmolality <275mosm/kg
• urine osmolality >100mosm/kg
• urine sodium >30mmol/l

Exclusion Criteria:

• acute (<72h) or transient hyponatremia
• severe symptomatic hyponatremia in need of hospital treatment
• diabetes mellitus type 1
• uncontrolled hypothyroidism
• uncontrolled adrenal insufficiency
• renal impairment (GFR <45ml/min)
• cardiac failure
• symptomatic liver disease / severe hepatic impairment (ALAT / aspartate transaminase (ASAT) > 3x upper limit)
• treatment with SGLT 2 inhibitors, lithium chloride, urea or glitazone
• severe immunosuppression
• pregnancy or breastfeeding
• palliative situation (end of life care)