From the Guidelines
Nexletol (bempedoic acid) is not FDA-approved for treating non-alcoholic fatty liver disease (NAFLD), and its timeframe for improving fatty liver disease is not well established. The primary approval for Nexletol is for lowering LDL cholesterol in patients with cardiovascular disease or heterozygous familial hypercholesterolemia. While some preliminary research suggests bempedoic acid may have beneficial effects on liver fat content due to its mechanism of inhibiting ATP citrate lyase and reducing hepatic lipogenesis, clinical studies specifically examining its timeline for liver improvement are limited 1. In patients taking Nexletol for its approved indication (typically 180 mg once daily), any potential improvements in liver health would likely occur gradually over months of treatment, similar to other lipid-lowering therapies. Patients with fatty liver disease should work with healthcare providers to develop a comprehensive treatment plan that includes lifestyle modifications such as:
- Weight loss: a weight loss of more than 5–7% can decrease intrahepatic fat content and inflammation, with greater weight loss correlating with greater histologic improvement 1
- Dietary changes: decreasing caloric intake by at least 30% or by approximately 750-1,000 kcal/day can result in improvement in insulin resistance and hepatic steatosis 1
- Exercise: regular physical activity, such as 150–300 minutes of moderate-intensity or 75–150 minutes of vigorous-intensity aerobic exercise per week, can improve NAFLD by reducing hepatic fat content and improving insulin sensitivity 1 Regular monitoring of liver function tests would be appropriate for patients with fatty liver disease who are prescribed Nexletol for its cholesterol-lowering effects. Key considerations for managing NAFLD include:
- Gradual weight loss of less than 1 kg/week is recommended over rapid weight loss in NAFLD patients with obesity 1
- A comprehensive treatment plan that incorporates lifestyle modifications and regular monitoring can help improve outcomes for patients with fatty liver disease.
From the Research
Timeframe for Nexletol to Improve Fatty Liver Disease
The timeframe for Nexletol (bempedoic acid) to improve fatty liver disease is not explicitly stated in the provided studies. However, the studies suggest that bempedoic acid can alleviate fatty liver disease in various animal models.
- In a dietary model of simple hepatic steatosis in female rats, bempedoic acid abrogates the accumulation of liver fat 2.
- In models of the advanced phases of nonalcoholic fatty liver disease (NAFLD), bempedoic acid reduces not only steatosis but also ballooning, lobular inflammation, and hepatic fibrosis 2.
- In a long-term high-fat diet-induced nonalcoholic steatohepatitis (NASH) animal model, bempedoic acid treatment for 5 weeks resulted in significant reductions in plasma ALT, AST, hepatic triglycerides, and total cholesterol, along with improvements in steatosis score and NAS score 3.
Mechanisms of Action
The mechanisms of action of bempedoic acid in improving fatty liver disease include:
- Inhibition of ATP-citrate lyase (ACLY) 2, 3, 4
- Inhibition of ketohexokinase 2
- Induction of patatin-like phospholipase domain-containing protein 3 2
- Increases in fatty acid β-oxidation activity and hepatic H2S production 2, 5
- Modulation of inflammatory and fibrotic genes 3
Clinical Relevance
While the provided studies demonstrate the potential benefits of bempedoic acid in improving fatty liver disease, the clinical relevance of these findings is still being investigated.