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SAN DIEGO — Patients with cirrhosis treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors show significant reductions in a range of portal hypertension complications and all-cause mortality compared with those not receiving the drugs, new research shows.

“Our study found that SGLT2 inhibitors were associated with fewer portal hypertension complications and lower mortality, suggesting they may be a valuable addition to cirrhosis management,” first author Abhinav K. Rao, MD, of the Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News.

The findings were presented at Digestive Disease Week (DDW) 2025.

Portal hypertension, a potentially life-threatening complication of cirrhosis, can be a key driver of additional complications including ascites and gastro-esophageal varices in cirrhosis.

Current treatments such as beta-blockers can prevent some complications, however, more effective therapies are needed.

SGLT2 inhibitors are often used in the treatment of cardiovascular disease as well as metabolic dysfunction–associated steatohepatitis (MASH)–mediated liver disease; research is lacking regarding their effects in portal hypertension in the broader population of people with cirrhosis.

“The therapeutic efficacy of SGLT2 inhibitors might be related to their ability to improve vascular function, making them attractive in portal hypertension,” Rao explained.

To investigate, Rao and colleagues evaluated data on 637,079 patients with cirrhosis in the TriNetX database, which includes patients in the United States from 66 healthcare organizations.

Patients were divided into three subgroups, including those with MASH, alcohol-associated, and other etiologies of cirrhosis.

Using robust 1:1 propensity score matching, patients in each subgroup were stratified as either having or not having been treated with SGLT2 inhibitors, limited to those who initiated the drugs within 1 year of their cirrhosis diagnosis to prevent immortal time bias. Patients were matched on other characteristics.

For the primary outcome of all-cause mortality, with an overall median follow-up of 2 years, patients prescribed SGLT2 inhibitors in the MASH cirrhosis (n = 47,385), alcohol-associated cirrhosis (n = 107,844), and other etiologies of cirrhosis (n = 59,499) groups all had a significantly lower risk for all-cause mortality than those not prescribed SGLT2 inhibitors (P < .05 for all).

SGLT2 Inhibitors in MASH Cirrhosis

Specifically looking at the MASH cirrhosis group, Rao described outcomes of the two groups of 3026 patients each who were and were not treated with SGLT2 inhibitors.

The patients had similar rates of esophageal varices (25% in the SGLT2 group and 22% in the no SGLT2 group), ascites (19% in each group), and a similar rate of 19% had hepatic encephalopathy (HE).

About 57% of patients in each treatment group used beta-blockers and 33% used glucagon-like peptide 1 (GLP-1) receptor agonists. Those with a history of liver transplantation, hemodialysis, or transjugular intrahepatic portosystemic shunt placement were excluded.

The secondary outcome results in those patients showed that treatment with SGLT2 inhibitors was associated with significantly reduced risks of developing portal hypertension complications including ascites, HE, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (P < .05 for all).

Esophageal variceal bleeding was also reduced with SGLT-2 inhibitors; however the difference was not statistically significant.

Effects Diminished With Beta-Blocker Treatment

In a secondary analysis of patients in the MASH cirrhosis group treated with one type of a nonselective beta-blockers (n = 509) and another nonselective beta-blockers (n = 2561), the beneficial effects of SGLT2 inhibitors on portal hypertension, with the exception of HE and SBP, were found to be somewhat diminished, likely because patients were already benefitting from the beta-blockers, Rao noted.

Other Groups

In outcomes of the non–MASH-related cirrhosis groups, patients prescribed SGLT2 inhibitors also had a reduced risk for specific, as well as any portal hypertension complications (P < .05), Rao noted.

Overall, the findings add to previous studies on SGLT2 inhibitors in MASH and expand on the possible benefits, he said.

“Our findings validate these [previous] results and suggest potential benefits across for patients with other types of liver disease and raise the possibility of a beneficial effect in portal hypertension,” he said.

“Given the marked reduction in portal hypertension complications after SGLT2 inhibitor initiation, the associated survival benefit may not be surprising,” he noted.

“However, we were intrigued by the consistent reduction in portal hypertension complications across all cirrhosis types, especially since SGLT-2 inhibitors are most commonly used in patients with diabetes who have MASH-mediated liver disease.”

‘Real World Glimpse’ at SGLT2 Inhibitors; Limitations Need Noting 

Commenting on the study, Rotonya M. Carr, MD, Division Head of Gastroenterology at the University of Washington, Seattle, said the study sheds important light on an issue previously addressed only in smaller cohorts.

“To date, there have only been a few small prospective, retrospective, and case series studies investigating SGTL2 inhibitors in patients with cirrhosis,” she told Medscape Medical News.

“This retrospective study is a real-world glimpse at how patients with cirrhosis may fare on these drugs — very exciting data.”

Carr cautioned, however, that, in addition to the retrospective study design, limitations included that the study doesn’t provide details on the duration of therapy, preventing an understanding of whether the results represent chronic, sustained use of SGLT2 inhibitors.

“[Therefore], we cannot interpret these results to mean that chronic, sustained use of SGTL2 inh is beneficial, or does not cause harm, in patients with cirrhosis.”

“While these data are provocative, more work needs to be done before we understand the full safety and efficacy of SGTL2 inhibitors for patients with cirrhosis,” Carr added.

“However, these data are very encouraging, and I am optimistic that we will indeed see both SGTL2 inhibitors and GLP-1s among the group of medications we use in the future for the primary management of patients with liver disease.”

The authors had no disclosures to report. Carr’s disclosures included relationships with Intercept and Novo Nordisk and research funding from Merck.