GLP-1RAs Reduce Risk of Hepatic Decompensation in Alcohol-Associated Liver Disease

Use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) may mitigate the risk of adverse liver outcomes in patients with alcohol-associated liver disease and type 2 diabetes, according to findings from a recent study.¹

The research was presented at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California, by Zayed Rashid, MD, a research fellow at The Ohio State University, with results suggesting the potential benefit of GLP-1RAs for mitigating the risk of outcomes like decompensation.¹

GLP-1RAs have grown increasingly popular in recent years, with one study leveraging records from more than 40 million US patients finding that more than 800,000 patients became new users of GLP-1RAs between 2011 and 2023.² In addition to indications for diabetes and obesity, the class of agents is also being studied for the treatment of liver diseases.

“Pathways involved in glycemic control and aversion to drinking alcohol can be a common target for glucagon-like peptide-1 receptor agonists,” Rashid and colleagues wrote.¹

To assess the impact of GLP-1RAs on adverse liver outcomes among patients with alcohol-associated liver disease and type 2 diabetes, investigators identified patients with type 2 diabetes who were newly diagnosed with alcohol-associated liver disease between 2013 and 2020 using the IBM-Marketscan database. Patients were categorized based on GLP-1RA exposure treated as a time-varying factor, and Overlap Propensity Score Weighting was used to account for confounders.¹

Poisson regression models were used to analyze the adjusted risk of adverse liver outcomes, a composite endpoint defined by the first occurrence of any hepatic decompensation, portal hypertension, hepatocellular carcinoma, or liver transplantation relative to GLP-1RA use.¹

Among 14,730 patients included in the study, the majority were male (66.2%) with a median age of 57 (interquartile range [IQR], 52 to 61) years. GLP-1RA exposure was observed among 2.2% of the cohort.¹

Overall, 32.0% of patients experienced hepatic decompensation, 15.9% had features of portal hypertension, 3.8% developed hepatocellular carcinoma, and 2.5% received a transplant.¹

Upon analysis, patients taking GLP-1RAs were less likely to experience hepatic decompensation (22.4% vs 32.2%) and hepatocellular carcinoma (0.3% vs 3.0%) compared with individuals not taking GLP-1RA (both P <.001). However, investigators did not observe an association between GLP-1RA use and the incidence of portal hypertension and liver transplant (P >.05).¹

After propensity score matching, 46 patients taking GLP-1RA had an adverse liver-related outcome over 379 person-years, with an absolute incidence rate difference of -9.0% (95% CI, -15.0% to -3.0%) and an adjusted incidence rate of 0.57 (95% CI, 0.39 to 0.82; P = .003) compared with non-GLP-1RA users.¹

When investigators assessed the composite adverse liver-related outcomes, patients exposed to GLP-1RA had lower hepatic decompensation with 33 events over 400 person-years and a lower adjusted incidence rate of 0.56 (95% CI, 0.36 to 0.86; P = .008) relative to the non-GLP-1RA group.¹

“GLP-1RA can potentially mitigate the risk of adverse liver outcomes, particularly decompensation, among patients with alcohol-associated liver disease,” investigators concluded.¹ “Future trials are needed to further investigate the role of GLP-1RA among patients with liver disease.”

References

1. ^{Rashid Z, Woldesenbet S, Khalil M, et al. Impact of Glucagon-like Peptide-1 Receptor Agonists on the Risk of Adverse Liver Outcomes among Patients with Alcohol-associated Liver Disease and Type 2 Diabetes. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}
2. ^{Campbell P. Surge in New GLP-1 Prescriptions Driven by Semaglutide's Popularity, Study Shows. HCPLive. July 22, 2022. Accessed November 18, 2024. https://www.hcplive.com/view/surge-in-new-glp-1-prescriptions-driven-by-semaglutide-s-popularity-study-shows}