Semaglutide Improves Liver Fibrosis in Patients with Metabolic Dysfunction-Associated Steatohepatitis

Semaglutide 2.4 mg (Wegovy; Novo Nordisk) achieved its primary end points in the ongoing ESSENCE trial (NCT04822181) by demonstrating statistically significant and superior improvement in liver fibrosis with no worsening of steatohepatitis in patients with metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced liver fibrosis (stage 2 or 3), according to a news release from Novo Nordisk.¹

Subcutaneous semaglutide injections can help improve liver fibrosis associated with MASH. | Image Credit: © K KStock | stock.adobe.com

Additionally, semaglutide 2.4 mg resolved steatohepatitis in patients with no worsening of liver fibrosis. At week 72 of the trial, 37.0% of patients treated with semaglutide achieved improvement in liver fibrosis with no steatohepatitis worsening compared with 22.5% on placebo. Furthermore, 62.9% of individuals treated with semaglutide 2.4 mg achieved resolution of steatohepatitis with no worsening of liver fibrosis compared with 34.1% on placebo.¹

In an important development, semaglutide 2.4 mg had a safe and well-tolerated profile in line with previous trials. The pivotal phase 3, 240-week, double-blinded trial evaluated the medication traditionally used for weight loss in 1200 adults with MASH. In part 1, the trial evaluated once weekly semaglutide 2.4 mg on liver tissue compared with placebo on top of standard of care.¹

“We are very pleased about the ESSENCE clinical trial results and the potential of semaglutide to help people living with MASH,” Martin Holst Lange, executive vice president and head of development at Novo Nordisk, said in the news release. He noted that, among individuals with overweight or obesity, 1-in-3 live with MASH.¹

“This has a serious impact on their health and represents a significant unmet need,” he continued.¹

Recent trials have evaluated glucagon-like peptide-1 (GLP-1) agonists as a potential treatment for patients with MASH. In July, results from a trial evaluating tirzepatide (Zepbound; Eli Lilly) indicated that patients receiving 5 mg, 10 mg, and 15 mg doses all had improvement in achieving MASH resolution with no worsening fibrosis.²

These results, combined with the positive results from the ESSENCE trial, demonstrate the strong potential of these therapies to treat patients with MASH. Semaglutide, like tirzepatide, is indicated—in conjunction with a reduced calorie diet and increased physical activity—for chronic weight management in adults with obesity or overweight. The properties of semaglutide are now showing promise in reducing liver fibrosis and poor outcomes associated with MASH.^1,2

MASH, a serious metabolic disease that affects the liver, can eventually replace liver tissue with scar tissue through the process of fibrosis. This leads to cirrhosis, which is irreversible liver damage that prevents the organ from functioning properly. It is unclear what cases MASH, but it is most seen in patients with obesity or overweight; therefore, its risk factors can include poor diet, diabetes, and high cholesterol.³

Oftentimes, those living with MASH experience no or few specific symptoms in the early disease stages, which can result in a delayed diagnosis. Pharmacists play a key role in ensuring that patients who may be at risk for developing MASH receive an early diagnosis and treatment. Now that therapies such as semaglutide and tirzepatide, which have become commonly available in many pharmacies across the country, are demonstrating efficacy in treating the disease, patients may soon have another option for treatment.^1,3

“In order for this disease to be truly treated and truly scaled to where it’s going to have the highest impact possible, it has to be addressed through managed care and has to be addressed through pharmacists being able to have coverage for medications for those most in need,” Jeff J McIntyre, vice president of liver health programs at the Global Liver Institute, said in an interview.³

REFERENCES

1. Novo Nordisk. Novo Nordsik A/S: Semaglutide 2.4 mg demonstrates superior improvement in both liver fibrosis and MASH resolution in the ESSENCE trial. News Release. Released November 1, 2024. Accessed November 8, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=171971

2. Gallagher A. Tirzepatide shows improvements in MASH without worsening fibrosis. Pharmacy Times. Published July 4, 2024. Accessed November 8, 2024. https://www.pharmacytimes.com/view/tirzepatide-shows-improvements-in-mash-without-worsening-fibrosis

3. Halpern L. NASH affects millions, but the future for treatment remains brighter than ever. Pharmacy Times. Published July 24, 2024. Accessed November 8, 2024. https://www.pharmacytimes.com/view/nash-affects-millions-but-the-future-for-treatment-remains-brighter-than-ever