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In preclinical models, researchers are exploring effects on endothelial function, blood pressure, lipid profiles, and inflammatory biomarkers
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Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is characterized by hepatic steatosis without external causes (e.g., alcohol use, viral hepatitis, medications).[49] MASLD is associated with various metabolic disorders and has a bidirectional relationship with T2DM, with either disease predisposing to the other.[36] Current management guidance from the American Association for the Study of Liver Diseases emphasizes lifestyle modification and optimization of comorbidities (e.g., diabetes, obesity) while acknowledging only a handful of drug therapies with proven benefit, including GLP-1RAs.[50] In the phase 2 LEAN trial (n=26), liraglutide reduced steatosis, fibrosis, and histologic steatotic hepatitis in participants with non-alcoholic steatohepatitis.[13] In a larger study of participants with MASLD on semaglutide, steatotic hepatitis resolution was dose-dependent.[20] A study of 1,197 patients with metabolic dysfunction-associated steatohepatitis and fibrosis found nearly two-thirds (63.9%) had resolution of steatohepatitis without worsening fibrosis with weekly semaglutide 2.4mg, compared to only 34.25% in the placebo group.[19] In individuals without diabetes but with MASLD, a subgroup analysis of 26 MASLD studies identified that GLP-1RAs reduced hepatic steatosis while potentially improving liver enzymes.[14] While tirzepatide has been less studied for MASLD, it may reduce absolute liver fat.[5] Overall, GLP-1RAs may have use in patients with MASLD regardless of T2DM status, but their effects in patients with cirrhosis and significant fibrosis need further investigation
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