New Guidance Updates Drug Treatments for Fatty Liver Disease (MASLD/MASH)

The global prevalence of Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly NAFLD, and its more severe inflammatory form, metabolic-dysfunction associated steatohepatitis (MASH), affects over 25% of adults, posing a significant health threat that can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Despite the urgent need, there has been a lack of comprehensive, updated pharmacological guidance for clinicians on effectively managing MASLD and MASH.

The guidance strongly recommends GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) as first-line pharmacological agents for patients with MASLD and MASH, particularly those with type 2 diabetes or obesity. These agents demonstrated significant improvements, with semaglutide showing up to 59% resolution of MASH (meaning the inflammation and ballooning of liver cells improved) without worsening fibrosis and tirzepatide achieving 55% resolution across various doses. PPAR-alpha/delta agonists like obeticholic acid were also recommended for MASH with fibrosis, showing a 20% improvement in fibrosis stage without worsening MASH after 72 weeks of treatment. The most impactful finding highlights that GLP-1 receptor agonists are now considered pivotal in MASLD/MASH management, offering substantial histological benefits beyond weight loss and glycemic control. Furthermore, SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) were recommended for patients with type 2 diabetes and MASLD, showing a 30-40% reduction in liver fat content and improvements in liver enzymes, though direct histological MASH resolution data is still emerging. The guidance also noted the potential role of vitamin E in non-diabetic MASH patients, demonstrating a 43% improvement in MASH histology compared to placebo in some studies.