FINDINGS from a new study reveal that mazdutide, a dual GLP-1 and glucagon receptor agonist, significantly reduced liver fat and improved metabolic markers in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity.
The multicentre, randomised phase 2 trial evaluated the effects of mazdutide over 48 weeks in adults with obesity and elevated liver fat content (≥5%) as measured by MRI. Participants received increasing doses of mazdutide (6 mg, 10 mg, or 16 mg) or placebo, alongside standard diet and exercise counselling.
Biopsy-Free Imaging Revealed Strong Liver and Metabolic Benefits
Of the 179 participants enrolled, 121 with baseline liver fat ≥5% were included in the MASLD analysis. After 32 weeks, liver fat content decreased significantly across all mazdutide groups compared with placebo, with reductions of up to 68.8%. More than 60% of participants on mazdutide 10 mg and 16 mg achieved complete steatosis resolution, compared with only 13% receiving placebo.
In addition to liver fat reduction, mazdutide improved alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting insulin, and insulin resistance (HOMA2-IR). Triglyceride levels also fell by over 30%, while markers of glucagon activity, such as beta-hydroxybutyrate, rose significantly, confirming the drug’s dual-receptor mechanism.
“In participants with obesity and baseline liver fat content ≥5%, mazdutide resolved steatosis in over 60% and 70% of participants at Weeks 32 and 48, respectively,” the authors reported. “Reductions in liver fat were strongly associated with body weight loss and improved insulin sensitivity.”
A Potential New Therapy for Obesity-Related Liver Steatosis
MASLD, formerly known as non-alcoholic fatty liver disease, affects up to a quarter of adults worldwide and is closely linked to obesity and insulin resistance. These findings suggest that mazdutide in MASLD could offer a promising new pharmacological approach, complementing lifestyle interventions.
Future studies will determine long-term outcomes and whether mazdutide’s dual-receptor activity can reduce the risk of progression to liver fibrosis or metabolic complications.
Reference
Harrison MNS et al. A phase 2, multicenter, randomized, placebo-controlled trial of Pemvidutide in metabolic dysfunction-associated steatohepatitis. Hepatol. 2025;DOI:10.1097/HEP.0000000000001589.
