SIG Greatest Hits: TLM 2025-MASLD SIG: Weight Independent Effects of Semaglutide in MASH

Video Transcription

Video Summary

Dr. Newsome from King's College Hospital presented a secondary analysis of the Phase III ESSENCE trial investigating semaglutide's effects on MASH (NASH with fibrosis). Semaglutide, a GLP-1 receptor agonist, achieved significant histological improvements and weight loss (~10.5%) compared to placebo. The analysis explored whether semaglutide’s liver benefits are solely due to weight loss or also from weight-independent mechanisms. Results showed that even modest weight loss (5-7%) led to substantial MASH resolution and fibrosis improvement, with semaglutide outperforming placebo at all weight loss thresholds. Causal mediation analyses indicated that semaglutide’s liver benefits derive roughly equally from weight-dependent and independent effects, suggesting additional mechanisms such as anti-inflammatory and insulin-sensitizing actions. These findings imply liver benefits from semaglutide even in patients with limited weight loss, emphasizing monitoring liver parameters beyond weight. The study generates hypotheses about non-weight-mediated pathways but acknowledges inherent limitations as a post hoc analysis.

Asset Subtitle

Talk delivered by Dr. Philip Newsome. Talk was part of the Clinical Plenary session.

Keywords

Semaglutide

MASH (NASH with fibrosis)

Weight loss

GLP-1 receptor agonist

Liver histological improvement