GLUCAGON LIKE PEPTIDE-1 RECEPTOR AGONISTS USE IS ASSOCIATED WITH LOWER MORTALITY AND IMPROVEMENT OF CARDIOVASCULAR OUTCOMES IN PATIENTS WITH MAFLD AND OBESITY: A MULTI-CENTER ANALYSIS.

Introduction
Metabolic dysfunction-associated fatty liver disease (MAFLD) affects one in four people globally and is the primary cause of chronic liver disease. The cornerstone of treatment focuses on lifestyle modifications, including weight loss, diet, and exercise. Only a few pharmacologic treatment options are considered in the current guidelines, such as vitamin E and pioglitazone. Glucagon like peptide-1 receptor agonists (GLP-1 RAs) have shown promising results in treating MAFLD. Therefore, we aim to evaluate the mortality rate and occurrence of cardiovascular (CV) events in this group of patients.
Methods
We performed a retrospective cohort study utilizing large population-based data from the TriNetX platform. We identified patients with obesity (BMI of 30 or greater) and MAFLD without bariatric surgery who received GLP-1 RAs between January 1, 2019, and May 31, 2023. This cohort of patients was matched with patients who did not receive GLP-1 RAs according to age, demographics, comorbidities, and medication by using 1:1 propensity matching. The primary endpoint was all-cause mortality, and the secondary endpoint was a composite of CV events. Cox proportional hazard models were used to estimate hazard ratios (HRs).
Results
A total of 137,008 adult patients with MAFLD and obesity were identified, 24,398 of these individuals were taking GLP -1 RAs; 20,981 out of 24,398 (mean [SD] age, 52.1 [12.9] years; 13,091 [62.4%] female) were matched with 20,981 individuals (mean [SD] age, 52.2 [14.9] years; 13,218 [63.0%] female) who did not take GLP-1 RAs. The GLP-1 RAs group had significantly lower all-cause mortality risk (Hazard Ratio [HR], 0.40; 95% Confidence Interval [CI], 0.35-0.46) and CV events including heart failure (HR, 0.76; 95% CI, 0.68-0.86), acute myocardial infarction (HR, 0.75; 95% CI, 0.63-0.90), unstable angina (HR, 0.76; 95% CI, 0.58-1.00), and cerebrovascular disease (HR, 0.91; 95% CI, 0.78-1.07) compared with the non-GLP-1 RAs group. No significant reductions in coronary revascularization (HR, 0.49; 95% CI, 0.04-5.46) and hypertension (HR, 1.14; 95% CI, 1.02-1.27) were identified.
Discussion
In this multicenter retrospective study, we found that patients with obesity and associated MAFLD who are on GLP-1 RAs have reduced rates of all-cause mortality and major cardiovascular events. Further prospective studies are needed to determine the mechanism for these clinical findings.