Natriuretic Effect of Dapagliflozin in Cirrhosis With Ascites: A Randomized, Placebo‐Controlled Crossover Trial

Background Ascites is a frequent complication of decompensated liver cirrhosis and is associated with a poor prognosis. Dapagliflozin, a sodium‐glucose cotransporter 2 (SGLT2) inhibitor, induces osmotic diuresis and natriuresis, with established use in heart failure. However, studies on SGLT2 inhibitors in cirrhotic patients with ascites are limited. Objectives The objective of this study is to evaluate changes in urine parameters in cirrhotic patients with ascites treated with dapagliflozin. Methods This randomized, double‐blind, placebo‐controlled, crossover trial enrolled 10 patients with Child–Pugh Class B or C cirrhosis who had persistently moderate or tense ascites. Participants received dapagliflozin or placebo for 4 weeks, followed by a 2‐week washout, and then crossed over to alternate treatment. The primary outcome was the change in 24‐h urine sodium (UNa) excretion on Days 0, 3, and 28. Secondary outcomes included changes in 24‐h urine volume (UV) and serum sodium. Results Dapagliflozin significantly increased 24‐h urinary sodium excretion at Day 3 compared with placebo (treatment difference +35.1 mmol/day; 95% CI 17.5–52.7; p < 0.001), indicating a transient natriuretic effect. This effect was not sustained at Day 28 ( p = 0.42). There were no significant changes in 24‐h UV or serum sodium at either time point. At the end of the dapagliflozin phase, 5 of 7 evaluable participants demonstrated improvement in ascites grade, whereas 2 did not. One serious adverse event occurred; one participant died during the washout period after completing the placebo phase due to variceal bleeding complicated by spontaneous bacterial peritonitis. Conclusions In cirrhotic patients with persistent ascites, dapagliflozin was associated with a transient increase in 24‐h urinary sodium excretion, without significant sustained effects on urine volume or serum sodium. Dapagliflozin was generally well tolerated in this small pilot trial. Trial Registration Thai Clinical Trial Registry: TCTR20241016007