Semaglutide, originally developed to manage obesity and diabetes, is now an FDA-approved treatment for metabolic dysfunction-associated steatohepatitis (MASH) – a serious liver condition. This marks a significant advancement, as only one other drug, resmetirom, currently holds FDA approval for MASH.
The Connection Between Fat and Liver Health
MASH develops when excess fat accumulates in the liver, leading to inflammation and potential scarring. Semaglutide doesn’t directly target the liver; instead, it works by reducing overall body fat and improving metabolic function. This indirect effect lowers liver fat, reduces inflammation, and helps prevent irreversible damage. As Dr. A. Sidney Barritt IV of UNC School of Medicine explains, the drug tackles underlying risk factors that impact liver health.
How Semaglutide Works
The drug’s effectiveness hinges on weight loss. Semaglutide suppresses appetite and slows digestion, facilitating weight reduction. Even modest weight loss (3–5% of body weight) can significantly decrease liver fat, while losing 7% can reduce inflammation. Clinical trials show patients taking 2.4mg of semaglutide weekly lose up to 10% of their body weight over 72 weeks.
But weight loss isn’t the only benefit. Semaglutide also improves metabolic health by regulating blood sugar, blood pressure, and cholesterol levels – all factors linked to MASH. The drug boosts insulin production and sensitivity, lowering blood glucose and improving control. This is particularly crucial since 35% of people with type 2 diabetes also have MASH, and many MASH patients are already prediabetic.
The Cyclical Relationship Between Blood Sugar and Liver Damage
High blood sugar accelerates liver damage by triggering insulin resistance and chronic inflammation, which drives fat buildup. This vicious cycle escalates liver scarring (fibrosis) and worsens insulin resistance. Semaglutide breaks this cycle by improving metabolic function.
FDA Approvals and Drug Variations
The FDA has approved Wegovy (semaglutide) specifically for MASH. Other semaglutide formulations, Ozempic and Rybelsus, are approved for type 2 diabetes but not yet for MASH directly, though they can help manage related metabolic conditions. High blood pressure and cholesterol levels exacerbate MASH, and semaglutide has demonstrated improvements in these areas too.
Long-Term Outlook
Research suggests semaglutide can resolve MASH in nearly two-thirds of patients. However, stopping treatment may lead to the condition’s return. The key takeaway is that semaglutide offers a significant indirect pathway to treat MASH by improving metabolic function and reducing liver fat accumulation.
The drug’s long-term effectiveness depends on continued use, reinforcing the need for sustainable lifestyle changes alongside medical intervention.
