SGLT-2 Inhibitors Reduce Liver-Related Complications in Cirrhosis, Study Suggests

Use of SGLT-2 inhibitors may reduce the incidence of serious liver events, including ascites, variceal development, hyponatremia, and all-cause mortality, in patients with cirrhosis receiving diuretic therapy, according to findings from a recent study.1

Leveraging data for more than 118,000 patients form 120 health care organizations in the TriNetX database, the retrospective cohort study found use of SGLT-2 inhibitors in patients with cirrhosis taking furosemide and spironolactone was associated with significantly lower rates of the composite outcome of serious liver events compared with patients with cirrhosis who did not receive SGLT-2 inhibitors. Additionally, these agents were associated with a reduced incidence of spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, paracentesis, hypoglycemia, and all-cause hospitalizations.1

According to the US Centers for Disease Control and Prevention, liver disease and cirrhosis affect an estimated 4.5 million adults and ranks as the ninth leading cause of death in the US.2 While treatment with diuretics is successful for many patients, some go on to develop refractory ascites and other major complications.1

“In the context of patients with cirrhosis, who are treated by diuretic therapy such as spironolactone and furosemide, the RAAS-modulating effects of SGLT-2 inhibitors could theoretically provide additional benefits. These benefits include improved volume status without exacerbating electrolyte imbalances, which is particularly relevant given the hemodynamic challenges in this patient population,” Dian Chiang, MD, MPH, Cleveland Clinic, and colleagues wrote.1 “The natriuretic and diuretic effects of SGLT-2 inhibitors could help manage fluid overload while potentially reducing the need for large-volume paracentesis.”

To address the lack of current data on the safety or efficacy of SGLT-2 inhibitors in patients with cirrhosis, investigators conducted a retrospective cohort study using data from more than 120 health care organizations within the TriNetX platform for adult patients with cirrhosis who were receiving furosemide and spironolactone from January 2013 to July 2021. 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, with follow-up ending in July 2024.1

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.1

Before propensity score matching, the study sample included 118,751 patients, 5330 of whom used SGLT-2 inhibitors and 113,421 of whom did not. After propensity score matching, 10,660 patients were included in the study; of these, 5330 used SGLT-2 inhibitors and 5330 (the control group) did not. Among the cohort, the mean age was 63.8 (standard deviation, 10.7) years, 57.8% of patients were male, and 66.3% were White.1

Results showed that compared with furosemide and spironolactone alone, use of SGLT-2 inhibitors with concurrent furosemide and spironolactone was associated with a statistically significant reduction in the risk of serious liver events (hazard ratio [HR], 0.68; 95% CI, 0.66-0.71; P <.001).1

Similarly, secondary outcomes’ analysis revealed use of SGLT-2 inhibitors was associated with a reduced risk of cirrhosis complications:

• 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)
• All-cause hospitalizations (HR, 0.67; 95% CI, 0.63-0.71)

“These findings suggest that SGLT-2 inhibitors may offer potential liver-related benefits in patients with cirrhosis,” investigators concluded.1 “Prospective trials are needed to further evaluate their safety and efficacy. Future studies should specifically examine changes in sodium levels following SGLT-2 inhibitor initiation, as well as the incidence of recurrent urinary tract infections and euglycemic diabetic ketoacidosis, given that these are known adverse effects of this drug class.”

References

1. Abu-Hammour MN, Abdel-Razeq R, Vignarajah A, et al. Sodium-Glucose Cotransporter 2 Inhibitors and Serious Liver Events in Patients With Cirrhosis. JAMA Network Open. 2025;8(6):e2518470. doi:10.1001/jamanetworkopen.2025.18470

2. US Centers for Disease Control and Prevention. Chronic Liver Disease and Cirrhosis. January 15, 2025. Accessed June 27, 2025. https://www.cdc.gov/nchs/fastats/liver-disease.htm