Endocrine Abstracts (2017) 49 EP889 | DOI: 10.1530/endoabs.49.EP889

Empagliflozin increases urinary volume output in healthy volunteers with artificial SIADH - a placebo-controlled double blind crossover study

Julie Refardt1, Bettina Winzeler1, Fabian Meienberg1, Deborah Vogt2 & Mirjam Christ-Crain1

1Department Endocrinology University Hospital Basel, Basel, Switzerland; 2Clinical Trial Unit University Hospital Basel, Basel, Switzerland.

Introduction: The Syndrome of inappropriate antidiuresis (SIADH) is the predominant cause of hyponatremia and its therapy options are unsatisfying. SGLT2-inhibitors have become a valuable treatment option for type 2 diabetes by increasing glucose excretion in the urine with concomitant osmotic diuresis. We therefore hypothesized that SGLT2-inhibitors could be a novel treatment option for SIADH.

Material and methods: We included 14 healthy volunteers in this prospective placebo controlled crossover study. To induce SIADH, participants were concomitantly administered desmopressin i.v. and hydrated. After the initial oral volume load and administration of desmopressin, a single dose of the study drug empagliflozin 25 mg or placebo was given in random order. The main outcomes were total urinary volume excretion, glucosuria and the area under the curve (AUC) of the serum sodium concentration. The outcome measures were obtained 2–8 hours after administration of the study drug.

Results: Fourteen participants (64% males), BMI 23.1 kg/m2 (±2.4), age 28.6 years (±9), with similar serum sodium levels on both study days (empagliflozin 140 mmol/l (±1.5) vs placebo 140 mmol/l (±1.3)) completed the study. Empagliflozin lead to significantly increased urinary volume excretion (579.3 ml ±194.8 vs 367.3 ml ±158.8; P=0.001) due to glucosuria (74.18 mmol ±22.3 vs 0.12 mmol ±0.04; P<0.001). There was no difference in the AUC of the serum sodium concentration under Empagliflozin compared to Placebo (Difference of AUC 0.2, CI -7.38; 6.98, P=0.96).

Conclusion: In healthy volunteers with artificially induced SIADH, empagliflozin increased volume excretion due to osmotic diuresis. Most probably due to the short treatment duration serum sodium levels remained unchanged. Additional studies in real live setting are needed to further examine the possible role of empagliflozin as a new treatment option for SIADH.

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