Sodium–glucose cotransporter-2 inhibitor use and clinical outcomes in patients with cirrhosis: a propensity-matched real-world cohort study

BACKGROUND: Patients with cirrhosis frequently have metabolic comorbidities that complicate treatment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular and renal benefits in type 2 diabetes, but their effects in cirrhosis remain uncertain. We evaluated the association between SGLT2 inhibitor use and clinical outcomes in patients with cirrhosis. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network. Adults with cirrhosis were stratified by SGLT2 inhibitor exposure. Propensity score matching balanced demographics, comorbidities, medication use, BMI, and laboratory variables. Outcomes included all-cause mortality, hepatic decompensation, acute kidney injury/hepatorenal syndrome (AKI/HRS), and hepatocellular carcinoma (HCC). RESULTS: After matching, 34 590 patients remained in each cohort. SGLT2 inhibitor use was associated with lower all-cause mortality [15.0 vs. 24.2%; hazard ratio: 0.67, 95% confidence interval (CI): 0.64-0.69, P < 0.001] and composite hepatic decompensation (28.6 vs. 36.3%; hazard ratio: 0.78, 95% CI: 0.76-0.80, P < 0.001). AKI/HRS was not increased on time-to-event analysis (hazard ratio: 0.99, 95% CI: 0.96-1.02, P = 0.346). HCC incidence was lower among SGLT2 inhibitor users (hazard ratio: 0.57, 95% CI: 0.39-0.86, P = 0.006). CONCLUSION: SGLT2 inhibitor use in patients with cirrhosis was associated with lower mortality, hepatic decompensation, and HCC incidence without increased AKI/HRS. These findings support prospective evaluation in selected patients with cirrhosis.