P2950 - GLP-1 Receptor Agonists Reduce the Risk of Hepatocellular Carcinoma and Cirrhosis in Patients With Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes

Saqr Alsakarneh, MD¹, Mahmoud Madi, MD², Mohammad Abuassi, MD³, Fouad Jaber, MD¹, Majd Khadra, MD⁴, Laith Numan, MD, MS², Wing-Kin Syn, MD, PhD^2
1University of Missouri - Kansas City School of Medicine, Kansas City, MO; ²Saint Louis University School of Medicine, St. Louis, MO; ³University of Central Florida, HCA Healthcare GME, Gainesville, FL; ⁴Detroit Medical Center/Wayne State University, Detroit, MI

Introduction: Glucagon-like peptide-1 receptors (GLP-1 Rs) are present in hepatocytes and have a direct role in decreasing nonalcoholic fatty liver disease (NAFLD). However, there is limited data on the effect of GLP-1 receptor agonists (GLP-1RAs) in reducing the HCC risk in patients with NAFLD. We aimed to investigate the influence of GLP-1RA use on the risk of HCC development in patients with NAFLD and type 2 diabetes mellitus (T2DM) using real-world evidence.

Methods: We conducted a retrospective cohort study using the TriNetX database to identify patients ≥18 years with NAFLD and T2DM. Treatment groups were divided into GLP-1RAs, metformin, and combination therapy of both GLP-1RAs and metformin. Patients with other chronic liver diseases and alcohol use disorders were excluded. We then matched these cohorts with patients who used oral hypoglycemics or insulin using 1:1 propensity score matching. The primary outcome was the HCC incidence rate. Secondary outcomes included the development of cirrhosis.

Results: Our cohorts included 52,476 patients with NAFLD and T2DM who used GLP-1RAs for at least 6 months (mean age 54.4 ± 12.1, 60.2% female, 68.2% White). After adjusting for confounders, there was a significant decrease in the odds of HCC development with GLP-1RAs (aOR: 0.41; 95% CI: 0.33 - 0.52; p = < 0.001) or combination therapy of GLP-1RAs and metformin (aOR: 0.35; 95% CI: 0.25 – 0.49; p = < 0.001) compared with oral hypoglycemics or insulin. When compared with patients treated with oral hypoglycemics and/or insulin, patients treated with GLP-1RAs had a statistically significant lower risk of cirrhosis (aOR: 0.75; 95% CI: 0.69 - 0.82; p = < 0.001). Using Logrank test model to compare the time to development of cirrhosis, patients treated with GLP-1RAs had a statistically significant longer time to cirrhosis (p< 0.0001) when compared to other hypoglycemics or insulin.

Discussion: Our results showed that GLP-1RAs were associated with decreased risk of cirrhosis and HCC in patients with NAFLD and T2DM. Further prospective studies are warranted to validate these findings and investigate the underlying mechanism of these findings.


Disclosures:


Saqr Alsakarneh, MD¹, Mahmoud Madi, MD², Mohammad Abuassi, MD³, Fouad Jaber, MD¹, Majd Khadra, MD⁴, Laith Numan, MD, MS², Wing-Kin Syn, MD, PhD². P2950 - GLP-1 Receptor Agonists Reduce the Risk of Hepatocellular Carcinoma and Cirrhosis in Patients With Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.