Semaglutide, the active ingredient in the widely recognized medications Ozempic and Wegovy, is on the verge of extending its applications in the medical field. In a significant development, a large-scale clinical trial published today revealed that semaglutide is effective in treating a severe and relatively prevalent form of liver disease known as metabolic dysfunction-associated steatohepatitis (MASH).

The Phase III clinical trial, which involved researchers from both the United States and the United Kingdom, was funded by Novo Nordisk, the pharmaceutical company behind semaglutide. The results of this trial indicate that participants receiving semaglutide showed substantial improvement compared to those on a placebo, marking a potential breakthrough in the treatment of MASH. This research could lead to semaglutide and similar GLP-1 receptor agonists becoming primary therapeutic options for this chronic condition, which remains a major health concern globally.

MASH is recognized as the most severe manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD). Both conditions are characterized by an excessive accumulation of fat in the liver, which can result in inflammation and, in severe cases, permanent liver damage such as cirrhosis. Historically, these diseases were referred to as nonalcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD), respectively.

MASLD is alarmingly prevalent, affecting approximately 25% of adults in the United States. Despite its high incidence, many individuals remain asymptomatic, making it difficult to diagnose until serious complications arise. While most individuals with MASLD do not progress to MASH, it still impacts around 6.5% of American adults and can lead to life-threatening conditions such as hepatocellular carcinomathe most common type of primary liver cancerand liver failure.

The causes of MASLD/MASH are multifactorial, with genetic predisposition playing a role. However, obesity and diabetes are significant contributors. Approximately 75% of individuals who are overweight and nearly 90% of those with severe obesity have MASLD, while an estimated one-third to two-thirds of individuals with type 2 diabetes also suffer from this condition. Given this close association, there has been considerable interest in whether semaglutide, along with other GLP-1 receptor agonists that are already approved for obesity and diabetes treatment, could also effectively manage MASLD/MASH.

Novo Nordisk's Phase III trial, named ESSENCE, enrolled roughly 800 patients diagnosed with MASH. Participants were randomly assigned to receive either semaglutide, at doses up to 2.4 milligrams (the highest approved dose for obesity treatment), or a placebo over a span of 72 weeks. All participants also received lifestyle counseling to complement the treatment.

At the conclusion of the study, nearly two-thirds of those receiving semaglutide experienced a resolution of their steatohepatitis, a significant improvement compared to the placebo group, where only half that percentage showed similar results. Additionally, participants on semaglutide exhibited a more pronounced reduction in liver fibrosis, characterized by scar tissue buildup, and experienced notable weight lossaveraging around 10%compared to those in the placebo group. The adverse effects of semaglutide were consistent with previous trials, primarily manifesting as gastrointestinal issues such as nausea, diarrhea, and vomiting.

"Having worked with GLP-1 treatments for sixteen years, I find these results tremendously promising. MASH is an escalating health crisis globally, and this trial brings real hope to patients suffering from this condition," remarked Philip Newsome, co-lead author and director of the Roger Williams Institute of Liver Studies at Kings College London, in a statement issued by the university. "However, it is crucial that we approach these findings with caution, as the analysis suggests that semaglutide can be a valuable tool in the fight against this advanced liver disease."

The findings from this trial were published on Wednesday in the prestigious New England Journal of Medicine, and they are expected to facilitate the approval of semaglutide for the treatment of MASH by the Food and Drug Administration (FDA). If approved, this would represent a significant advancement for a condition that, until recently, lacked any available drug treatments. Notably, just over a year ago, the FDA granted approval for Rezdiffra, the first drug targeting this condition, developed by Madrigal Pharmaceuticals.

Rezdiffra operates through a different mechanism, targeting a specific receptor that prevents fat accumulation in the liver without inducing weight loss. This differentiation is likely beneficial as it offers healthcare providers and patients additional treatment options, particularly for those who may not respond positively to one medication over another.

Moreover, other GLP-1 receptor agonists, as well as drugs that mimic different hormones associated with weight management, are currently undergoing testing for their efficacy in treating MASH. Should these trials yield favorable results, we may witness a transformative shift in the management of MASH, much like the profound impact these medications have already had on the treatment of obesity.