Empagliflozin Increases Short-Term Urinary Volume Output in Artificially Induced Syndrome of Inappropriate Antidiuresis

Julie Refardt; Bettina Winzeler; Fabian Meienberg; Deborah R Vogt; Mirjam Christ-Crain

doi:10.1155/2017/7815690

Empagliflozin Increases Short-Term Urinary Volume Output in Artificially Induced Syndrome of Inappropriate Antidiuresis

Int J Endocrinol. 2017:2017:7815690. doi: 10.1155/2017/7815690. Epub 2017 Dec 20.

Authors

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

Affiliations

¹ Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
² Clinical Trial Unit, Department Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.

Abstract

Objective: Syndrome of inappropriate antidiuresis (SIADH) is the predominant cause of hyponatremia, but treatment options are unsatisfying. SGLT2 inhibitors increase urinary glucose excretion with concomitant osmotic diuresis. We therefore hypothesized SGLT2-inhibitors as a novel treatment for SIADH.

Design: Double-blind placebo-controlled randomised crossover study in 14 healthy volunteers.

Methods: We induced an artificial SIADH model by administration of desmopressin and overhydration. Afterwards, empagliflozin 25 mg or placebo was given in random order. The main outcomes were total urinary excretion, glucosuria, and the area under the curve (AUC) of serum sodium concentration. Outcome measures were obtained 2-8 hours after administration of study drug.

Results: 14 participants (64% males), BMI 23 kg/m² (±2.4), aged 28.6 years (±9), completed the study. Empagliflozin led to significantly increased total urinary excretion (579.3 ml (±194.8) versus 367.3 ml (±158.8); treatment effect 158 ml (CI 48.29, 267.74), p = 0.017) due to glucosuria (74.18 mmol (±22.3) versus 0.12 mmol (±0.04); treatment effect (log scale) 2.85 (CI 2.75, 2.96), p < 0.001). There was no difference in the AUC of serum sodium concentration (treatment effect 0.2 (CI -7.38, 6.98), p = 0.96).

Conclusion: In our SIADH model, empagliflozin increased urinary excretion due to osmotic diuresis. Due to the short treatment duration, serum sodium levels remained unchanged. Real-live studies are needed to further examine empagliflozin as a new treatment for SIADH.