DAY 1: Higher Doses of Semaglutide Boost Resolution of Metabolic Dysfunction-Associated Steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH) is a rapidly growing public health concern driven by the global epidemics of obesity, type 2 diabetes, and dyslipidemia. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown significant benefits in reducing weight and preventing cardiovascular events in individuals with metabolic dysfunction. Earlier this year, semaglutide gained regulatory approval in the United States for the treatment of adults with non-cirrhotic MASH and moderate-to-advanced liver fibrosis (stages F2 and F3). As the newcomer in the treatment of MASH, semaglutide has become the object of multiple studies and analyses designed to assess its efficacy in patients with biopsy-proven MASH across different dosing regimens.
 
Madhu Adusumilli, MD, and colleagues at the University of Central Florida, in Ocala, Florida conducted a meta-analysis of five randomized controlled trials including 1,366 adults with MASH to evaluate the dose-dependent effects of semaglutide relating to different outcomes. Those included resolution of MASH without worsening of fibrosis, improvement of stage 1 fibrosis without worsening of MASH, body weight, liver enzymes, and magnetic resonance imaging proton density fat fraction (MRI-PDFF). The results showed that semaglutide achieved resolution of MASH in higher proportions compared with placebo, showing a clear dose-dependent effect. Higher doses (0.4 mg/day or 2.8 mg/week) increased resolution rates by approximately 26% compared to the standard dosing of 2.4 mg per week used in treating diabetes and obesity, without causing an increase in adverse events. Although improvements in fibrosis did not reach statistical significance, semaglutide showed consistent benefit for weight reduction, hepatic enzyme levels, and MRI-PDFF.

“Semaglutide is effective in resolving MASH with robust histologic and metabolic improvements, with higher doses providing greater benefits without additional safety concerns,” Adusumilli said during a poster presentation at the 2025 Annual Scientific Meeting of the American College of Gastroenterology (ACG 2025). “While fibrosis outcomes remain inconclusive, semaglutide’s favorable safety and efficacy profile strongly supports its role as a promising therapy for MASH.” 

A separate meta-analysis featured at ACG 2025, which included 13 studies with 1,334 patients, also showed that semaglutide significantly reduced hepatic steatosis, BMI, HbA1c, and levels of liver enzymes. Similarly to Adusumilli and colleagues, the investigators found that the effect of semaglutide on fibrosis was limited and inconsistent, signaling the need for trials that utilize histological endpoints and longer follow-up periods.