Journal Article Multicenter Study Ppublish
PubMed: 42736811 DOI: 10.1097/MD.0000000000050733
Clinical outcomes associated with GLP-1 receptor agonist use in metabolic dysfunction-associated steatohepatitis: A multinational cohort study.
Medicine (Baltimore) 105(37):e50733
Authors: Sajjad Ahmed Khan, Anuj Subedi, Anurag Marasini, Alisha Shrestha, Saurav Jha, Arjun Kandel, Krity Basnet, Shreya Karki, Meraj Kamal, Sadab Khan, Huma Kausar, Surya Bahadur Parajuli, Dushyant Singh Dahiya
Affiliations
- Department of Internal Medicine, Birat Medical College Teaching Hospital, Morang, Nepal.
- Department of Internal Medicine, University of Maryland Capital Regional Health, Largo, MD.
- Department of Internal Medicine, West Virginia University Health System Princeton Community Hospital, Princeton, WV.
- Department of Internal Medicine, MedStar Georgetown University Hospital, Baltimore.
- Department of Internal Medicine, Stoony Brook University, NY.
- Department of Internal Medicine, Baptist Memorial Hospital-North Mississippi Oxford Hospital.
- Department of Internal Medicine, Jersey City Medical Center.
- Department of Internal Medicine, Nepal Medical College Teaching Hospital, Kathmandu, Nepal.
- Department of Internal Medicine, B.P. Koirala Institute of Health Sciences, Dharan, Nepal.
- Department of Internal Medicine, Liceo de Cagayan University.
- Department of Internal Medicine, Karnali Academy of Health Sciences, Nepal.
- Department of Community Medicine, Birat Medical College Teaching Hospital, Morang, Nepal.
- Department of Gastroenterology and Hepatology, Turkey Creek Medical Center, Tennova Healthcare, Knoxville, TN.
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is an important progressive liver disorder that can lead to hepatic decompensation, hepatocellular carcinoma (HCC), and premature death. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated beneficial effects on metabolic dysfunction and liver histology; however, their relationship with major long-term hepatic outcomes in routine clinical practice has not been fully established. A retrospective multicenter cohort study was conducted using a large real-world health database. Adults with MASH were classified according to whether they had documented exposure to GLP-1 RAs. The 2 groups were balanced using 1:1 propensity score matching based on demographic variables, coexisting conditions, and concomitant therapies. The outcomes evaluated were ascites, HCC, and all-cause mortality, with comparative effects reported as risk differences (RDs) and 95% confidence intervals (CIs). The initial study population comprised 1434,086 individuals with MASH, including 168,740 GLP-1 RA users and 1265,346 individuals without GLP-1 RA exposure. After matching, 168,733 patients were retained in each cohort with comparable baseline characteristics. Exposure to GLP-1 RAs was associated with fewer cases of ascites (RD - 0.013; 95% CI - 0.014 to - 0.012; P < .001) and lower all-cause mortality (RD - 0.022; 95% CI - 0.023- - 0.021; P < .001). A statistically significant increase in HCC incidence was observed among GLP-1 RA users; however, the magnitude of the absolute difference was minimal (RD 0.000; 95% CI 0.000-0.001; P = .025). Among patients with MASH, GLP-1 RA exposure was associated with a lower incidence of ascites and reduced mortality in this large real-world matched cohort. While a statistically significant difference in HCC occurrence was detected, its negligible absolute magnitude suggests limited clinical relevance. These findings support the potential role of GLP-1 RAs as beneficial and hepatically safe therapies in patients with MASH.
MeSH
Glucagon-Like Peptide 1, Mortality, Carcinoma, Hepatocellular, Glucagon-Like Peptide-1 Receptor, Incidence, Non-Alcoholic Fatty Liver Disease, Cohort Studies, Liver, Therapeutics, Ascites