Empagliflozin versus dapagliflozin in patients with liver cirrhosis: A comparative real-world study on hepatic decompensation.

Abstract

Background and aim: Sodium-glucose cotransporter-2 inhibitors may improve outcomes in liver cirrhosis, but comparative evidence between individual agents is limited. We compared real-world outcomes of empagliflozin versus dapagliflozin in adults with liver cirrhosis.

Materials and methods: We conducted a multicenter retrospective cohort study using the TriNetX US Collaborative Network (69 healthcare organizations). Adults with cirrhosis who were newly prescribed empagliflozin or dapagliflozin after the diagnosis of cirrhosis between March 1, 2013 and January 1, 2025, were included. Propensity score matching (1:1) was used to balance baseline characteristics. Outcomes were assessed from day 1 after the index prescription through 5 years. Primary outcomes were all-cause mortality and all-cause hospitalization. Secondary outcomes included hepatic decompensation events. Tertiary outcomes included prognostic hepatic and renal biomarkers. Safety outcomes included the incidence of acute kidney injury, urinary tract infection, and diabetic ketoacidosis.

Results: Before matching, 17,700 empagliflozin users and 8,619 dapagliflozin users were identified; 7,852 patients remained in each cohort after matching. Five-year mortality was similar between groups (12.7% vs. 12.6%; odds ratio [OR]: 1.012, 95% confidence interval [CI]: 0.921-1.112; p=0.8075), as was the risk of hospitalization (14.7% vs. 13.4%; OR: 1.105, 95% CI: 0.94-1.30; p=0.216). Empagliflozin was associated with lower rates of hepatic encephalopathy (4.0% vs. 4.7%; OR: 0.84; p=0.0295), hepatorenal syndrome (1.0% vs. 1.6%; OR: 0.614; p=0.0007), and paracentesis (2.9% vs. 3.7%; OR: 0.785; p=0.0083). Albumin levels were higher and bilirubin levels were lower with empagliflozin (p<0.01 for both). Safety outcomes were similar between groups.

Conclusion: In matched adults with cirrhosis, empagliflozin and dapagliflozin demonstrated comparable five-year mortality and hospitalization rates. However, empagliflozin was associated with fewer selected decompensation events without an increase in adverse events.