SGLT-2 Inhibitors for Ascites Management in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Available Evidence.

Abstract

Goal: The goal is to systematically evaluate the efficacy and safety of SGLT-2 inhibitors (SGLT2i) versus standard therapy for ascites management in liver cirrhosis.

Background: SGLT2i promote natriuresis and osmotic diuresis, offering potential therapeutic benefits for fluid overload in cirrhosis, similar to their established role in heart failure. However, high-quality comparative evidence remains limited.

Study: A systematic search of PubMed, Scopus, Cochrane, Embase, and Web of Science was conducted through October 2025 following PRISMA 2020 guidelines. Eligible studies included randomized controlled trials and prospective comparative studies enrolling adults (≥ 18 years) with confirmed cirrhosis treated with dapagliflozin or empagliflozin, alone or alongside standard therapy, versus placebo or standard care for ≥ 2 weeks. The primary outcome was complete ascites resolution; secondary outcomes included mortality, body weight, eGFR, and serum creatinine and sodium levels.

Results: Three studies (two RCTs and one prospective trial; n = 382) were included, comprising 241 patients receiving SGLT2i and 141 controls. SGLT2i significantly increased complete ascites resolution (OR: 2.39, 95% CI: 1.47-3.90; p < 0.001; I ² = 15%) and reduced body weight (MD: -4.86 kg, 95% CI: -7.57 to -2.14; p = 0.0005; I ² = 0%). No significant differences were observed in eGFR, serum creatinine, serum sodium, or mortality within the RCT subgroup (OR: 1.60, 95% CI: 0.53-4.87; I ² = 0%); the overall three-study pool (OR: 0.27, 95% CI: 0.13-0.56; I ² = 87%) was driven by the nonrandomized trial (test for subgroup differences p = 0.001). The only placebo-controlled RCT reported significantly higher rates of AKI (50% vs. 15%, p = 0.04) and infections (55% vs. 20%, p = 0.04) in the SGLT2i arm.

Conclusions: SGLT2i improved ascites resolution and body weight without changes in routinely measured renal parameters, but unresolved AKI and infection signals and very low GRADE certainty for mortality preclude routine clinical use. SGLT2i should be considered only as individualized investigational therapy under close monitoring pending larger RCTs. PROSPERO (CRD420261303781).