The Ozempic universe expands: These drugs also treat fatty liver disease

The Ozempic universe is expanding — with no end in sight. These groundbreaking drugs, which help patients lose around 15% of their body weight, have already transformed the treatment of diabetes and obesity, and their scope continues to grow.

According to new research published Wednesday in The New England Journal of Medicine, they also show promise in treating advanced stages of fatty liver disease linked to metabolic dysfunction. This condition, affecting one in three adults, is marked by fat buildup in the liver and, in its more severe forms, includes fibrosis and inflammation that can lead to cirrhosis or liver cancer.

The new study reveals that semaglutide — the active ingredient in this first generation of anti-obesity drugs — not only halts the progression of the disease, but may even reverse it.

In two-thirds of patients treated in the clinical trial, the study’s authors report, these drugs — also known as GLP-1 receptor agonists, because they mimic hormones that naturally create a feeling of fullness — were able to reduce the inflammation responsible for fat buildup in the liver. Fibrosis also improved in 37% of participants. The researchers emphasize that this discovery opens the door to a new therapeutic landscape for a serious condition that, until now, lacked a substantial pharmacological arsenal.

Semaglutide — sold under brand names Ozempic and Wegovy — mimics peptides in the body that help regulate, among other things, satiety: the molecule acts in the gut and sends signals to the brain to induce a sense of fullness. But, as experts point out, the peptide targeted by these drugs is present throughout the body — as are the receptors that respond to it. This means the drug’s effects may go beyond just weight loss.

“[With these drugs] visceral fat is reduced, but we have receptors for these molecules in almost every organ, and they will also have an effect,” reflects Andreea Ciudin, head of the Comprehensive Obesity Treatment Unit at Vall d’Hebron Hospital in Barcelona and a member of the board of directors of the Spanish Society for the Study of Obesity. “We know there are 230 direct complications related to obesity. Dysfunctional adipocytes create the breeding ground for many diseases. All that remains is to conduct trials [to verify the impact of the drugs at these levels].”

The research published in The New England Journal of Medicine is a prime example. Fatty liver disease is closely linked to a group of metabolic disorders — high blood pressure, elevated blood sugar, obesity, and high levels of cholesterol and triglycerides — that significantly increase the risk of cardiovascular problems, stroke, and diabetes.

Around 30% of the global population suffers from fatty liver disease associated with metabolic dysfunction, and although in most people it may develop without symptoms, experts estimate that between 25% and 30% of those affected will progress to the most advanced stage of the disease. This involves a cascade of liver damage that can become life-threatening: the excessive accumulation of fat in the liver prevents the organ from storing and metabolizing it properly, leading liver cells to suffer damage and die, which in turn causes inflammation. In response to this injury, the liver initiates a scarring process (fibrosis), but this scar tissue cannot perform the same functions as healthy tissue, and liver function begins to fail.

The article published on Wednesday presents interim results from an international phase 3 clinical trial led by researchers from King’s College London and Virginia Commonwealth University, and funded by Novo Nordisk — the pharmaceutical company that sells Ozempic. The scientists recruited 800 individuals with advanced stages of fatty liver disease associated with metabolic dysfunction and divided them into two groups: one received semaglutide, while the other was given a placebo.

After 72 weeks of treatment, the results showed that inflammation caused by fat accumulation resolved in nearly 63% of the patients treated with the innovative drug, and their fibrosis did not worsen; in the placebo group, only 34% experienced this improvement.

The study also showed that in 37% of the patients treated with semaglutide, liver scarring (fibrosis) improved — compared to 22.4% in the placebo group. In addition, the drug was found to restore other liver markers and reduce body weight by 10.5%, versus just 2% in the placebo group.

Philip Newsome, director of the Roger Williams Institute of Hepatology at King’s College and one of the study’s authors, stated in a press release that the results are “extremely promising.” The scientist emphasized that fatty liver disease associated with metabolic dysfunction is a growing global problem, and this clinical trial offers “real hope” for patients in the most advanced stages of the condition. “While the results should be interpreted with caution, they show semaglutide can be a powerful therapeutic option for this advanced liver condition,” he added.

Regarding the patients who did not respond as strongly in this preliminary analysis, the researcher notes: “It’s important to keep in mind that these data only reflect 72 weeks, so it’s possible that with longer treatment, more patients may see benefits.”

Vanesa Bernal, a board member of the Spanish Association for the Study of the Liver, says that hepatologists had been closely following this research. These results were expected, she explains, because earlier phases of the trial had already yielded “spectacular data.” “And furthermore,” she adds, “hepatologists know that by correcting metabolic conditions and losing weight [something semaglutide often achieves], the liver improves significantly.”

Fighting fibrosis

Ciudin is also not surprised by the results: “It was something we were expecting.” The endocrinologist admits that, until now, studies using semaglutide for this disease had not shown an impact on fibrosis, though they had shown effects on fat accumulation in the liver. That alone, she says, already offered a glimmer of hope for researchers. “What concerns us most is fibrosis, but with the same molecule, in a phase 2 trial, the effect didn’t show — perhaps because of the study design or treatment duration. So seeing in this trial that fibrosis can actually be reversed brings hope,” she reflects.

However, she clarifies that this study found positive results in patients with intermediate or advanced stages of fibrosis (grades II and III), but it is still unknown whether the drug would be effective in the most severe stage (grade IV) or once cirrhosis is already established.

The authors themselves note in the article: “Although semaglutide can be safely used in patients with cirrhosis, its efficacy in this population has not been established.”

The clinical trial is ongoing: researchers plan to recruit a total of 1,200 participants across 37 countries and continue for five years to assess cirrhosis-free survival over that period. But the Ozempic universe doesn’t end there.

Alcohol-related fatty liver

Newsome notes that trials are also underway to study semaglutide in patients with alcohol-related liver damage: “We are awaiting these data. Other studies have shown that semaglutide/GLP-1 medications can alter or reduce alcohol craving, which may be useful in this setting.”

Along these lines, Bernal points out that the drugs’ potential to help patients with addictions is also being investigated: “These medications not only act on the pancreas, but also in the brain, in the hypothalamus: they decrease satiety, but they also act on reward and punishment mechanisms. Combining these two things would be wonderful because it would not only reduce liver fat, but would also control cravings in patients with problematic alcohol use,” she reflects.