In a retrospective cohort of 242 patients with fatty liver disease and T2DM, GLP-1 RA users showed less liver fibrosis progression compared to non-users based on FIB-4 scores, though differences were small.
32.6% on GLP-1 RA showed less fibrosis progression79 of 242 patients with fatty liver disease and T2DM were taking GLP-1 drugs, and they showed less liver scarring progression compared to the 163 untreated controls
What the researchers found
Patients treated with GLP-1 RAs showed less liver fibrosis progression (by FIB-4 score) compared to untreated controls in a retrospective cohort of 242 T2DM patients with steatotic liver disease, though differences were modest.
Why it matters
Fatty liver disease affects roughly 25% of the global population and is even more common in diabetes. Few approved treatments exist for liver fibrosis. If GLP-1 drugs — already widely used for diabetes — also slow liver scarring, it provides a compelling additional reason to choose them as first-line diabetes therapy in patients with fatty liver disease.
The numbers in context
Retrospective study period: January to December 2021. Compared GLP-1 RA users to non-users among patients with T2DM and NAFLD/NAFL/NASH.
How the study worked
Retrospective cohort study of adult patients with T2DM and NAFLD/NAFL/NASH (Jan-Dec 2021). Excluded: hepatitis B/C, pioglitazone use. 79 GLP-1 RA users compared to 163 controls. Primary outcome: change in FIB-4 score. Secondary: NAFLD Fibrosis Score (NFS). Follow-up labs 3-15 months after baseline.
Who was studied
Adults with T2DM and steatotic liver disease (NAFLD/NASH)
What this study cannot tell us
Retrospective, non-randomized design — patients who received GLP-1 RAs may differ systematically from controls. Small sample size and short follow-up (3-15 months). FIB-4 is an indirect surrogate for fibrosis, not direct liver biopsy measurement. The baseline GLP-1 RA group had higher NFS, suggesting potentially more advanced disease. Confounding by other medications, lifestyle changes, and weight loss not fully controlled.
How to read the evidence
Preliminary evidence from a retrospective cohort study with inherent confounding and small effect sizes. Supports the hypothesis but cannot establish causation. Randomized trials are needed.
When this study was published
Published in 2024, contributing to the rapidly growing evidence base for GLP-1 drugs in liver disease ahead of results from definitive randomized trials.
The bigger picture
GLP-1 drugs are emerging as potential therapies for liver disease in addition to diabetes and obesity. The recent approval of resmetirom for NASH and ongoing trials of semaglutide for liver fibrosis reflect growing interest in this area. This retrospective study adds real-world supporting evidence, though the definitive answers will come from randomized trials like the ongoing ESSENCE trial of semaglutide for NASH.
Questions still open
- Will randomized trials like ESSENCE confirm that semaglutide slows liver fibrosis in NASH patients?
- Is the protective effect driven by weight loss, improved insulin resistance, or direct hepatoprotective GLP-1R signaling?
- Should GLP-1 drugs be preferred over other diabetes medications in patients with concurrent fatty liver disease?
Common questions
Can GLP-1 drugs actually treat fatty liver disease?
What is the FIB-4 score?
Read the original research
Impact of GLP-1 Receptor Agonist Use in Patients With Steatotic Liver Disease and Type 2 Diabetes: A Retrospective Cohort Study.
Journal of pharmacy practice, 37(6), 1297-1302
Citation
Wood, Marci; Kennedy, Amanda G; Khan, Sidra; Hitt, Juvena R; Davis, Kayla; Reddy, Sheela S; Gilbert, Matthew P. (2024). Impact of GLP-1 Receptor Agonist Use in Patients With Steatotic Liver Disease and Type 2 Diabetes: A Retrospective Cohort Study.. Journal of pharmacy practice, 37(6), 1297-1302. https://doi.org/10.1177/08971900241253661