SGLT-2 inhibitors may provide liver-related benefits to patients with cirrhosis

The use of a sodium-glucose cotransporter 2 (SGLT-2) inhibitor helps lower the incidence of serious liver events among patients with cirrhosis who are receiving diuretic therapy, according to a study.

In a large propensity-score matched cohort, the risk of serious liver events—defined as a composite of ascites, esophageal or gastric varices with or without bleeding, hyponatremia, or all-cause mortality— was reduced by 32 percent among patients receiving add-on SGLT-2 inhibitor vs those on furosemide plus spironolactone alone (hazard ratio [HR], 0.68, 95 percent confidence interval [CI], 0.66–0.71; p<0.001). [JAMA Netw Open 2025;8:e2518470]

Results for the secondary outcomes also favoured the addition of an SGLT-2 inhibitor, with lower risks of hepatorenal syndrome (HR, 0.47, 95 percent CI, 0.40–0.56), spontaneous bacterial peritonitis (HR, 0.55, 95 percent CI, 0.46–0.65), paracentesis (HR, 0.54, 95 percent CI, 0.50–0.60), variceal bleeding (HR, 0.79, 95 percent CI, 0.73–0.84), hypoglycemia (HR, 0.75, 95 percent CI, 0.62–0.91), and all-cause hospitalizations (HR, 0.67, 95 percent CI, 0.63–0.71).

Furthermore, in the subgroup of patients with MELD 3.0 scores not more than 15, the use of an SGLT-2 inhibitor in addition to furosemide and spironolactone showed a risk-reducing benefit across outcomes including the composite of serious liver events (HR, 0.82, 95 percent CI, 0.74–0.90; p<0.001), paracentesis (HR, 0.67, 95 percent CI, 0.47–0.96), and all-cause hospitalizations (HR, 0.86, 95 percent CI, 0.74–0.99).

“It is important to note that, although not statistically significant, the HR for hepatic encephalopathy was greater than 1 (HR, 1.35, 95 percent CI, 1.00–1.83) in our subgroup analysis. This is consistent with findings from a previous trial on biliary cirrhotic rats, suggesting that SGLT-2 inhibitors should be used with caution in patients with cirrhosis who are at an increased risk for hepatic encephalopathy,” the investigators noted. [J Pharmacol Exp Ther 2022;383:25-31]

Taken together, the present study suggests a potential role for SGLT-2 inhibitors in cirrhosis management, they said. “While recent studies have highlighted the benefits of SGLT-2 inhibitors in patients with heart failure and diabetes, our findings extend these potential benefits to include liver-related complications in a population with cirrhosis.”

The investigators postulated that the observed associated benefits of SGLT-2 inhibitors in patients with cirrhosis may be attributed to the drugs’ capacity for net free water excretion, “resulting from glucosuria and osmotic diuresis, in addition to their RAAS-modulating effects reported in previous studies.” [Front Med (Lausanne) 2021;8:777861; Front Pharmacol 2022;13:800490; J Am Heart Assoc 2020;9:e016270]

Indeed, there is growing evidence supporting the potential therapeutic value of SGLT-2 inhibitors in patients with advanced liver disease, with improvements reported in both liver-related outcomes and overall survival. [BMC Gastroenterol 2023;23:450; Gut 2024;73:2054-2061]

For the present study, the investigators used data from more than 120 healthcare organizations within the TriNetX platform. They identified 10,660 propensity-matched patients (mean age 63.8 years, 57.8 percent male, 66.3 percent White), of which 5,330 used SGLT-2 inhibitors and 5,330 did not.