Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin

Abstract

Background Empagliflozin increases sodium levels in patients with a chronic syndrome of inappropriate antidiuresis (SIAD) and dapagliflozin increases apelin levels in patients with diabetes mellitus. Exogenous apelin increases sodium levels in rats with SIAD. We aimed to investigate whether an increase in plasma apelin concentration may contribute to the efficacy of empagliflozin in SIAD. Methods Post-hoc secondary analysis of a double-blind, crossover, placebo-controlled trial performed from 12/2017 to 08/2021 at the University Hospital Basel, Switzerland, investigating the effect of 4 weeks treatment with empagliflozin 25 mg/day as compared to placebo in 14 outpatients with chronic SIAD (NCT03202667). The objective was to investigate the effect of empagliflozin on plasma apelin and copeptin concentrations and their ratio. Results Fourteen patients, 50% female, with a median [IQR] age of 72 years [65–77] were analyzed. Median apelin concentration was 956 pmol/l [853, 1038] at baseline. Median [IQR] apelin relative changes were +11% [0.7, 21] and +8% [-5, 25] (P = 0.672) at the end of the placebo and empagliflozin phases, respectively. Median copeptin concentration was 2.6 [2.2, 4.5] pmol/l at baseline and had a relative change of +5 [-2. 11]% and +25% [10, 28] (P = 0.047) over the placebo and empagliflozin phases, respectively. Conclusions Empagliflozin did not lead to significant changes in apelin or the apelin/copeptin ratio in patients with chronic SIAD, but led to an increase in copeptin. This suggests that the efficacy of empagliflozin in SIAD is independent of apelin and is not blunted by the adaptative increase in copeptin.