S732 Cardiovascular and Hepatic Outcomes of Tirzepatide vs Aspirin in Patients With Obesity and Metabolic Dysfunction-Associated Steatohepatitis: A Real-World Analysis

Introduction: Several studies have shown the superior cardiovascular and hepatic benefits of tirzepatide compared to other incretin-based medications for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Furthermore, recent clinical trials indicate that a daily aspirin regimen can significantly lower liver fat content. In the pursuit of a sustainable treatment for MASLD/MASH, this study examines the efficacy and safety profiles of tirzepatide and aspirin on the progression of MASLD/MASH and its related complications. Methods: Using the Trinetx database, we identified patients with obesity (body mass index ≥30 kg/m²) and MASLD and/or MASH from January 1, 2019, to December 31, 2023. Two cohorts were examined: the tirzepatide group and the aspirin group. We included only participants who began either medication after being diagnosed with MASLD or MASH. Patients on other GLP-1Ras besides tirzepatide and those with other causes of liver disease were excluded. Propensity score matching (PSM) was utilized to balance baseline characteristics. Primary outcomes include the risk of major adverse cardiovascular events (MACE), all-cause mortality, progression to fibrosis, hepatic complications, and hepatic medication use. Results: Before PSM, 9,636 and 73,071 patients were analyzed in the tirzepatide and aspirin groups, respectively. After PSM, 9,542 patients were identified in both groups. Tirzepatide demonstrates therapeutic advantages across multiple clinical domains, showing significant reductions in all- cause mortality (0.2% vs 2.5%) and major adverse cardiovascular events (MACE) (1.2% vs 7.5%). Tirzepatide also exhibits a superior hepatic safety profile with less medication use (2.4% vs 12.5%) and fewer complications. Although not statistically significant, tirzepatide was also associated with a reduced risk of progression to cirrhosis (1.0% vs 1.5%) (P = 0.215). Conclusion: Our analysis revealed that tirzepatide provides significant benefits over aspirin for patients with obesity and MASLD/MASH. While cirrhosis progression shows a non-significantly increased risk, the overwhelming cardiovascular and survival benefits, along with superior prevention of hepatic complications, are noteworthy. Additionally, the significant risk reductions across primary endpoints suggest that tirzepatide offers substantial net clinical benefit in this high-risk population.