Abstract
SAFETY AND EFFICACY OF DAPAGLIFLOZIN IN RECURRENT ASCITES: A PILOT STUDY
Background: The pathophysiology of ascites in cirrhosis entails vasodilatation with the consequential activation of sympathetic nervous system and renin-angiotensin-aldosterone system, leading to retention of sodium and water. Dapagliflozin, a sodium glucose linked transporter-2 inhibitor, induces natriuresis and is beneficial in patients with heart failure. We hypothesised that a similar natriuretic effect may improve mobilization of ascites in patients with cirrhosis. In this pilot study, we evaluated the efficacy and safety of dapagliflozin in patients with cirrhosis with recurrent ascites.
Methods: Forty patients with recurrent ascites and cirrhosis were randomized 1:1 in a double blinded fashion to receive either dapagliflozin (10 mg/day) with standard medical therapy (Group A) or placebo with standard medical therapy (Group B). The primary outcome was control of ascites at 6-months. Secondary outcomes were urine output, 24-hour urinary sodium, estimated glomerular filtration rate, HbA1c, mean arterial pressure, Child Turcotte Pugh (CTP), model for end stage liver disease (MELD) scores and survival at 6-months, incidence of acute kidney injury (AKI), infections, hepatic encephalopathy, hyponatremia, hypokalemia, hepatocellular carcinoma, diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic coma.
Results: The 2 groups were comparable at baseline. Complete and partial control of ascites at 6-months were seen in 3 (15%) and 11 (55%) patients in Group A which was significantly better than that in Group B (complete control: 0, partial resolution: 7 (35%), p=0.01). Change in urinary sodium was significantly higher in Group A [13.3 (-10.9 to 30.1) vs -4.4 (-16.4 to 5.6), p<0.001]. However, there was no difference in change in urine output, estimated glomerular filtration rate, HbA1c, mean arterial pressure, CTP or MELD scores between the groups at 6-months. Incidence of AKI (50% vs 15%, p=0.04) and infections (55% vs 20%, p=0.04) were significantly higher in Group A but there was no difference in hepatic encephalopathy, hyponatremia, hypokalemia, hepatocellular carcinoma, diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic coma. Survival at 6-months was similar in the 2 groups (65% vs 68.2%, p=0.75).
Conclusion: Significantly better control of ascites and higher natriuresis are observed with dapagliflozin. However, it does not improve disease severity scores or survival, and is associated with increased AKI and infections (NCT05014594).