GLP-1 AGONISTS CAN PREVENT LIVER DISEASE PROGRESSION IN PATIENTS WITH METABOLIC AND ALCOHOL-ASSOCIATED LIVER DISEASE (METALD).

Background: The American Association for Study of Liver Diseases (AASLD) recently proposed new nomenclature to characterize steatotic liver diseases. According to this classification, patients with both metabolic dysfunction and moderate to severe alcohol use were categorized as separate entity , metabolic and alcohol-associated liver disease (MetALD). GLP-1 agonists (GLP1a) have shown effectiveness in control of certain components of metabolic dysfunction. Also, recent animal studies suggested GLP-1a can reduce alcohol consumption and addictive behavior. No human study has investigated the outcomes of GLP-1a use in patients with MetALD.

Aim: To assess the benefit of GLP-1a to prevent hepatic decompensation in patients with MetALD.

Methods: This is a retrospective cohort study in patients presented to Stanford Health Care in both inpatient and outpatient settings between 2017 and 2021. Patients diagnosed with fatty liver disease who have at least one metabolic risk factor [body mass index (BMI) >25, hemoglobin A1c (HgbA1c) >5.7%, hypertension, hyperlipidemia including triglyceride >150 mg/dL or HDL less than 40 mg] AND have a history of excessive alcohol use were included in the study. Patients with a diagnosis of decompensated cirrhosis at the time of entry to the study were excluded. Patients were categorized based on exposure to GLP-1a including Semaglutide, or Tirzepatide for at least 24 weeks versus no exposure to GLP-1a. High dimensional propensity scoring was utilized to compare the outcomes of the two groups. Data collection and analysis were performed using Atropos Health.

Results: Overall, 2171 patients with fatty liver disease due to MetALD were identified during the study time frame. Patients were followed for an average of 1172 days. Of them, 58 patients received GLP-1a therapy, whereas 2113 patients had no GLP-1a exposure. Among patients who received GLP-1a, only 4 (6.9%) patients developed decompensated cirrhosis, compared to 394 (18.6%) patients in the control group. At the end of the follow-up period, GLP1a use was associated with a reduction in hyperglycemia; changes in HgbA1c were -1.54 and +0.1 in patients receiving GLP1a and the control group, respectively. Similarly, alanine transferase (ALT) improved in patients being treated with GLP1a (delta-ALT in GLP1a: -24.4 vs. control: -4.5). After propensity score matching, patients who received GLP1a therapy showed a significantly lower rate of decompensated cirrhosis [HR, 0.23 (95%CI, 0.08-0.71), p=0.01].

Conclusions: GLP1a is a promising therapy in patients diagnosed with steatotic liver disease and may also improve outcomes in those with MetALD. If these results are confirmed, randomized clinical trials are warranted to confirm the beneficial effect of GLP1a in this population.