Semaglutide for Nonalcoholic Steatohepatitis

In NAFLD, an abnormal blood lipid profile is a strong predictor for NASH. In particular, triglycerides are an important marker of NASH among patients with NAFLD. Metabolic syndrome and other factors are also associated with NASH. The combination of abnormal blood lipids and metabolic syndrome is associated with an increased risk of cirrhosis in men and NAFLD in women.

Nonalcoholic steatohepatitis affects approximately 2.4% of the U.S. population. The average rate in the United States is about 1.7% of the population. Men and women are affected equally. The highest incidence of disease is found in the 50 to 60-year-old age group in the United States and in Caucasians.

Obesity may be the most important cause of steatosis and NASH. steatosis often precedes NASH, but NASH may cause steatosis. Steatosis is more important than insulin resistance as the cause of NASH; insulin resistance does not explain why only 10% of people with normal cholesterolesters develop NASH.

To summarize, NASH often progresses towards cirrhosis; individuals with NASH may also develop liver cancer due to prolonged and severe inflammation, which can result in severe liver damage. Furthermore, patients with NASH have an increased risk for developing cirrhosis, hepatocellular carcinoma, and type 2 diabetes compared to the general population. To identify individuals at risk of NASH, clinicians need to be aware of the following factors: duration and severity of alcohol use; BMI; presence of metabolic syndrome abnormalities; triglyceride levels; fasting free fatty acid levels; liver damage on imaging studies; and markers of insulin resistance.

While treatment may be less common, several studies that are in aggregate indicate that nonalcoholic steatohepatitis responds well to weight loss with or without medication and that the effects are usually sustained over many months or years.

Findings from a recent study provides data that suggest the presence of a subgroup of patients with NASH in whom long-term disease remission can be achieved. In some cases, it is possible for patients to achieve a great improvement, even a clinical and histological remission of the NASH pattern. Prospective studies involving larger samples and longer follow-up are needed to confirm these preliminary results.

We expect that semaglutide is an effective and safe treatment in NAFLD patients with a body mass index level ≥30 kg/m(2), as proven by previous studies.

Semaglutide is being studied in several Phase I and II clinical trials in patients with various types of diabetes, as well as patients with chronic kidney disease and advanced non-alcoholic steatohepatitis. These studies will be critical to define the role of semaglutide in patients with end organ disease, including renal and liver, and in patients with diabetes with and without comorbidities.

Clinicians might find using semaglutide in combination with other agents used in the treatment of diabetes a useful strategy to reduce the risk of hepatic failure. It is unclear whether this interaction is statistically significant.

semaglutide is effective in the treatment of obesity in both short-acting and long-acting forms. With semaglutide, significant and durable weight loss was observed after 20 weeks of treatment. In addition to weight loss, decreased serum triglycerides, improved lipid profiles, and increase in HOMA-IR are also observed. The increased adiponectin may also result in improvement in glycemic control.

In order to develop effective therapy for NASH, more large trials will be needed in the near future. One of the important obstacles to developing a therapy is that NASH can be developed in different ways. The definition of the disease will also become clearer. Because most of the treatments have been used for other diseases, one needs to further investigate more targeted therapies to treat NASH.