Sodium-Glucose Cotransporter 2 Inhibitors and Serious Liver Events in Patients With Cirrhosis

Importance Cirrhosis is a significant global health burden, with serious liver-related complications leading to high morbidity and mortality. Effective therapeutic options to mitigate these complications remain limited. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, primarily used in diabetes and heart failure management, may offer additional liver-related benefits. Objective To evaluate the association between SGLT-2 inhibitor use and the risk of serious liver events in patients with cirrhosis receiving furosemide and spironolactone. Design, Setting, and Participants This cohort study used data from over 120 health care organizations within the TriNetX platform. Adult patients with cirrhosis who were receiving furosemide and spironolactone from January 2013 to July 2021 were included. Patients who were receiving SGLT-2 inhibitors plus furosemide and spironolactone were matched with a control group of patients who were receiving furosemide and spironolactone alone according to age, demographics, and comorbidities using 1:1 propensity matching. Each patient was followed up for 3 years; follow-up ended on July 11, 2024. Exposure Use of SGLT-2 inhibitors. Main Outcomes and Measures The primary outcome was a composite of serious liver events defined as incidence of ascites, variceal development, hyponatremia, or all-cause mortality. Secondary outcomes included incidence of variceal bleeding, paracentesis, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, hypoglycemia, and all-cause hospitalizations. Continuous variables were compared using an independent-samples t test; categorical variables were compared using the Pearson χ 2 test. Results Among 10 660 propensity-matched patients (mean [SD] age, 63.8 [10.7] years; 57.8% male), those receiving SGLT-2 inhibitors had a lower incidence of serious liver events compared with control patients (hazard ratio [HR], 0.68 [95% CI, 0.66-0.71]; P < .001). Secondary outcomes included hepatorenal syndrome (HR, 0.47 [95% CI, 0.40-0.56]), spontaneous bacterial peritonitis (HR, 0.55 [95% CI, 0.46-0.65]), paracentesis (HR, 0.54 [95% CI, 0.50-0.60]), variceal bleeding (HR, 0.79 [95% CI, 0.73-0.84]), hypoglycemia (HR, 0.75 [95% CI, 0.62-0.91]), and all-cause hospitalizations (HR, 0.67 [95% CI, 0.63-0.71]), all of which were associated with a reduced risk among those in the SGLT-2 inhibitors group. Conclusions and Relevance In this cohort study of adults with cirrhosis who were receiving diuretic therapy, the findings suggest that SGLT-2 inhibitor use was associated with a lower incidence of serious liver events. These findings further suggest a potential role for SGLT-2 inhibitors in cirrhosis management.