Sodium-glucose cotransporter 2 inhibitors may decrease risk of serious liver events in patients with cirrhosis

1. Use of Sodium-Glucose Cotransporter 2 (SGLT-2) inhibitors among adults with cirrhosis receiving diuretic therapy was associated with lower incidence of serious liver events, defined as the incidence of ascites, variceal development, hyponatremia, or all-cause mortality.

Evidence Rating Level: 2 (Good)

Liver cirrhosis ranks as the 11th most common cause of mortality globally. Among patients with cirrhosis, 10% develop refractory ascites, defined as ascites that cannot be mobilized even with diuretic therapy. More effective therapies are thus needed to improve patient outcomes. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors may offer additional liver-related benefits through their natriuretic and diuretic effects. Due to limited research on the efficacy of SGLT-2 inhibitors in patients with cirrhosis, this study evaluated the association between SGLT-2 inhibitor use and the risk of serious liver events in patients with cirrhosis on diuretic therapy. This retrospective cohort study used data from over 120 healthcare organizations within the TriNetX platform. Adult (>19 years) patients with cirrhosis receiving diuretic therapy (furosemide and spironolactone) from January 2013 to July 2021 were included and followed up for 3 years. 1:1 propensity score matching was used to balance baseline characteristics between patients receiving SGLT-2 inhibitors plus furosemide and spironolactone, and those receiving furosemide and spironolactone alone. The primary outcome was a composite variable of serious liver events, including the incidence of esophageal or gastric variceal development, ascites, hyponatremia, or all-cause mortality. Out of the 10 660 propensity-matched patients (mean [SD] age, 63.8 [10.7] years; 57.8% male), 5330 used SGLT-2 inhibitors and 5330 did not (control group). Patients receiving SGLT-2 inhibitors had a lower incidence of serious liver events (hazard ratio [HR], 0.68 [95% CI, 0.66-0.71) compared to control patients. Use of SGLT-2 inhibitors was also associated with reduced risk of 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]). Overall, this study found that use of SGLT-2 inhibitors was associated with a lower incidence of serious liver events among adults with cirrhosis receiving diuretic therapy compared to those receiving diuretic therapy alone. Future studies are needed to confirm study findings and compare different types and dosages of SGLT-2 inhibitors to optimize treatment for patients with cirrhosis.

Click to read the study in JAMA Network Open

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