Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr;61(7):1163-1174.
doi: 10.1111/apt.18502. Epub 2025 Jan 10.

Glucagon-Like Peptide-1 Receptor Agonists and Liver Outcomes in Patients With MASLD and Type 2 Diabetes

Chia-Chih Kuo  1 , Min-Hsiang Chuang  1 , Chun-Hsien Li  2 , Ya-Wen Tsai  3 , Po-Yu Huang  1 , Hsing-Tao Kuo  1   4 , Chih-Cheng Lai  4   5
Affiliations

Glucagon-Like Peptide-1 Receptor Agonists and Liver Outcomes in Patients With MASLD and Type 2 Diabetes

Chia-Chih Kuo et al. Aliment Pharmacol Ther. 2025 Apr.

Abstract

Background and aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated long-term liver benefits in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). However, no direct comparison between these therapies has been conducted. This study aimed to compare major adverse liver outcomes (MALOs) between GLP-1 RAs and SGLT2is in patients with MASLD and T2D.

Methods: Using the TriNetX Research Network, a multinational and multi-institutional database, we identified adults with MASLD and T2D who received their first prescription for either a GLP-1 RA or an SGLT2i between January 2010 and June 2023. We conducted a propensity score-matched (PSM) cohort study comparing new users of GLP-1 RAs and SGLT2is. The primary outcome was the risk of MALOs, a composite endpoint consisting of decompensated cirrhosis events, hepatocellular carcinoma, and liver transplantation. Secondary outcomes included all-cause mortality and individual components of the primary outcome.

Results: This study included 15,176 pairs of patients treated with either a GLP-1 RA or a SGLT2i. The adjusted hazard ratio (HR) for MALO associated with GLP-1 RAs relative to SGLT2is was 0.84 (95% confidence interval [CI]: 0.73-0.97; incidence rate: 88.9 versus 105.3 events per 10,000 person-years), primarily driven by reduction in decompensated cirrhosis events (adjusted HR: 0.83, 95% CI: 0.71-0.96). GLP-1 RAs were associated with lower all-cause mortality (adjusted HR: 0.84, 95% CI: 0.75-0.94).

Conclusion: GLP-1 RAs are associated with better long-term liver outcomes compared to SGLT2is in patients with MASLD and T2D.

Keywords: GLP‐1 receptor agonist; MASLD; SGLT‐2 inhibitor; major adverse liver outcomes.

PubMed Disclaimer

References

    1. D. Q. Huang, H. B. El‐Serag, and R. Loomba, “Global Epidemiology of NAFLD‐Related HCC: Trends, Predictions, Risk Factors and Prevention,” Nature Reviews. Gastroenterology & Hepatology 18, no. 4 (2021): 223–238, https://doi.org/10.1038/s41575‐020‐00381‐6.
    1. A. C. Sheka, O. Adeyi, J. Thompson, B. Hameed, P. A. Crawford, and S. Ikramuddin, “Nonalcoholic Steatohepatitis: A Review,” Journal of the American Medical Association 323, no. 12 (2020): 1175–1183, https://doi.org/10.1001/jama.2020.2298.
    1. E. Harris, “FDA Okays First Drug for Scarring From Fatty Liver Disease,” Journal of the American Medical Association 331, no. 17 (2024): 1439, https://doi.org/10.1001/jama.2024.5154.
    1. Z. M. Younossi, P. Golabi, L. de Avila, et al., “The Global Epidemiology of NAFLD and NASH in Patients With Type 2 Diabetes: A Systematic Review and Meta‐Analysis,” Journal of Hepatology 71, no. 4 (2019): 793–801, https://doi.org/10.1016/j.jhep.2019.06.021.
    1. Z. M. Younossi, A. B. Koenig, D. Abdelatif, Y. Fazel, L. Henry, and M. Wymer, “Global Epidemiology of Nonalcoholic Fatty Liver Disease: Meta‐Analytic Assessment of Prevalence, Incidence, and Outcomes,” Hepatology 64, no. 1 (2016): 73–84, https://doi.org/10.1002/hep.28431.

Substances

LinkOut - more resources