Can lowering triglycerides help treat metabolic dysfunction-associated steatohepatitis?

Metabolic dysfunction-associated steatohepatitis (MASH) is a liver condition where fat buildup causes inflammation and scarring. High triglycerides often go hand-in-hand with MASH. Lowering triglycerides with medications like fibrates, omega-3s, or newer drugs may reduce liver fat and improve liver health. However, it is not yet proven that triglyceride-lowering alone can reverse MASH in most people. Your doctor can help you understand if this approach is right for you.

What the research says

A review of triglyceride-lowering therapies found that drugs such as fibrates, omega-3 fatty acids, pemafibrate, and newer agents like pegozafermin (an FGF21 analog) show promise in reducing liver fat and improving liver enzymes and fibrosis markers in MASH ¹. These therapies work by lowering triglycerides in the blood and inside the liver, which may directly reduce hepatic steatosis and inflammation ¹.

A network meta-analysis of phase 2-3 trials in MASH found that therapies targeting metabolic dysfunction and insulin sensitivity, including some that lower triglycerides, showed the most consistent benefits for MASH resolution and fibrosis improvement ². However, even with treatment, 35%-70% of participants did not meet biopsy endpoints, meaning many people still had active disease ².

Another study on semaglutide, a drug that lowers blood sugar and promotes weight loss, found that higher doses and greater weight loss were linked to lower risk of steatohepatitis and other liver outcomes ⁸. While semaglutide is not primarily a triglyceride-lowering drug, it does improve lipid profiles, and the study suggests that weight loss and metabolic improvements are key drivers of liver benefit ⁸.

Research on FGF21 analogs, which lower triglycerides, shows they can reverse MASH in mice by acting on the brain to reduce liver fat production and directly on liver cells to lower cholesterol ⁹. In humans, these agents are being tested and show promise for reducing liver fat and improving MASH ¹¹¹.

Overall, the evidence suggests that lowering triglycerides can help treat MASH, but it is often part of a broader strategy that includes weight loss, improving insulin sensitivity, and reducing inflammation ¹²⁵.

What to ask your doctor

• Could a triglyceride-lowering medication like a fibrate or omega-3 supplement be helpful for my MASH?
• Are there newer drugs, such as FGF21 analogs or APOC3 inhibitors, that I might consider for my liver condition?
• How do my current triglyceride levels compare to targets that might benefit my liver health?
• Would combining a triglyceride-lowering drug with lifestyle changes or other MASH treatments improve my outcomes?
• What are the potential side effects of triglyceride-lowering therapies, especially for my liver?