Sodium-Glucose Cotransporter-2 Inhibitors Are Associated with Improved Survival in Patients with Cirrhosis.

BACKGROUND AND AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may have favorable hepatic effects, but long-term outcomes in cirrhosis are uncertain. We investigated the relationship between SGLT2i exposure and 5-year outcomes among adults with cirrhosis.

METHODS

We performed a retrospective cohort study in the TriNetX US Collaborative Network (March 2013- January 2025). Adults (≥18 years) with cirrhosis were classified as SGLT2i users (first exposure on/after cirrhosis diagnosis) or non-users (no SGLT2i exposure) and propensity score matched 1:1. Outcomes were assessed over 5 years beginning 1 day after index. Primary outcomes were all-cause mortality and hospitalization burden (inpatient encounters per patient). Secondary outcomes included hepatic decompensation complications and prespecified adverse events; tertiary outcomes were the most recent liver- and kidney-related laboratory values during follow-up.

RESULTS

After matching, 24,559 patients were included per cohort. SGLT2i use was associated with lower all-cause mortality (11.8% vs 26.0%; OR=0.381, 95%CI: 0.363-0.399; p<0.001) and fewer hospitalizations (mean 3.6±10.7 vs 5.4±13.4; p<0.001). Composite hepatic decompensation was less frequent (OR=0.617, 95%CI: 0.580-0.656; p<0.001), including lower odds of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome; hepatic encephalopathy did not differ. Acute kidney failure and urinary tract infection were less frequent, while diabetic ketoacidosis did not differ. Laboratory profiles favored SGLT2i use (lower aspartate aminotransferase and bilirubin, higher albumin, lower international normalized ratio, and improved renal indices).

CONCLUSIONS

In this matched real-world cohort, SGLT2i exposure after cirrhosis diagnosis was associated with an improved 5-year survival, fewer hospitalizations, and fewer decompensation events.