DAY 3: Glucagon-Like Peptide-1 Receptor Agonists May Improve Survival for Patients with Cirrhosis

Glucagon-like peptide-1 (GLP-1) receptor agonist therapy may benefit patients with liver disease even after they develop cirrhosis, potentially reducing their risk of liver decompensation and mortality, according to an analysis presented at the 2026 Annual Scientific Meeting of the American College of Gastroenterology in Nashville, Tennessee. 

GLP-1 receptor agonists have demonstrated hepatoprotective effects and have been shown to reduce the risk of progression to cirrhosis in patients with early or non-cirrhotic metabolic dysfunction-associated steatotic liver disease (MASLD) [Amorim Moreira Alves G et al. Chronic Dis Transl Med 2026;12(2):85-99]. However, real-world data have suggested that the protective benefits against liver-related progression and mortality are largely seen when treatment begins before the development of cirrhosis. 

In a retrospective cohort study of more than 3,000 patients treated at the Guthrie Robert Packer Hospital in Sayre, Pennsylvania between January 2022 and April 2026, researchers took a closer look at the effects of GLP-1 therapy in patients with cirrhosis with different underlying etiologies. The analysis included 3,222 patients with cirrhosis. Of those, 542 were using GLP-1 receptor agonists for indications such as diabetes or weight management. Patients who were not on GLP-1 therapy had a lower body mass index (BMI) and a lower proportion of diabetes compared with GLP-1 users. 

The primary analysis showed that the crude mortality rates were much lower in patients with GLP-1 receptor agonist exposure (8.1%) than in those who had not used GLP-1 agonists (25.3%). After adjusting for all confounding factors, patients treated with GLP-1 receptor agonists had a 72% reduction in mortality risk compared to those without exposure. Liver-related events were documented as the main cause of death in both groups. 

GLP-1 receptor agonist users also had less healthcare utilization, with lower rates of all-cause and liver-related hospital admissions and shorter hospital stays compared to non-users. The protective effects of GLP-1 agonists persisted after a sensitivity analysis was performed to reduce selection bias, with GLP-1 users showing a 57% reduction in the risk of death compared to the other group. The benefit appeared to be independent of diabetes status and baseline severity of liver disease.

“The fact that the GLP-1 [receptor agonist] benefits persisted even after adjusting for MASLD suggests that GLP-1 effect is independent of baseline cirrhosis severity,” lead author Abdullah Sultany, MD, a resident at Guthrie Robert Packer Hospital, said during a plenary session. “These results demonstrate a substantial and consistent protective signal worthy of prospective investigation.” 

Sultany noted that, due to its retrospective nature, the analysis could not establish causality, and it merely identified an association between GLP-1 receptor agonist use and a reduction in mortality risk. Moreover, he clarified, “the analysis did not differentiate by etiology of cirrhosis. This is a significant limitation, because different etiologies may respond differently to GLP-1 receptor agonist therapy.” Stratifying patients according to etiology could clarify the mechanisms by which GLP-1 receptor agonists may offset the impact of cirrhosis. 

Further investigations are also needed to support optimal patient selection and choice of therapeutic agent. Sultany pointed out that, if the findings regarding the protective effects of this therapy are confirmed, the use of GLP-1 receptor agonists could mark a paradigm shift in cirrhosis management.