Global 
Deutschland Liver and Bile
Gut. 2025;74(2):284-294
Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease
Objective: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
Design: This population-based cohort study was conducted using a nationwide healthcare claims database (2014–2022) of Korea. The authors included individuals with MASLD (aged ≥ 40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).
Results: After 1:1 propensity score matching, the authors included 22,550 patients who initiated SGLT-2i and GLP-1RA (median age, 57 years, 60% male), and 191,628 patients who initiated SGLT-2i and TZD (median age, 57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR = 0.93, 95% CI: 0.76–1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR = 0.77, 95% CI: 0.72–0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR = 0.87, 95% CI: 0.80–0.94; female: HR = 0.62, 95% CI: 0.55-0.69).
Conclusions: In this nationwide cohort study, sodium-glucose cotransporter-2 inhibitors were associated with a lower risk of hepatic decompensation events in patients with metabolic dysfunction-associated steatotic liver disease compared with thiazolidinedione, while demonstrating similar effectiveness to glucagon-like peptide-1 receptor agonists.