Randomised trial comparing weight loss through lifestyle and GLP-1 receptor agonist therapy in people with MASLD

作者：Ahmad Moolla, Toryn Poolman, Nantia Othonos, Jiawen Dong, Kieran Smith, Thomas Cornfield, Sarah J. White, David Ray, Sofia Mouchti, Ferenc E. Mózes, Helena Thomaides‐Brears, Stefan Neubauer, Jeremy Cobbold, Leanne Hodson, Jeremy Tomlinson · 发表于：JHEP Reports · 年份：2025 · DOI：10.1016/j.jhepr.2025.101363 · 被引用次数：25 · 研究领域：Liver Disease Diagnosis and Treatment、Diabetes Treatment and Management、Liver Disease and Transplantation

Background & Aims: Glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies deliver histological benefit in people with metabolic dysfunction-associated steatotic liver disease (MASLD). Multiple mechanisms may be important including weight loss, improved glycaemic control and putative direct tissue-specific actions. Following cessation of GLP1-RA therapy, weight regain is common. To dissect the mechanisms underpinning their benefits, we conducted a prospective, randomised, experimental medicine study in people with MASLD, comparing GLP-1RA treatment (liraglutide) to matched lifestyle-induced weight loss and assessed the impact of treatment withdrawal. Methods: lipogenesis (DNL), liver magnetic resonance imaging, body composition, adipose tissue RNA sequencing, circulating proteome, and stool microbiome analysis. Participants were randomised to lifestyle (∼500 kcal energy deficit) or GLP1-RA treatment for 12 weeks, after which investigations were repeated, and treatment stopped; investigations were also repeated 12 weeks after treatment withdrawal. Results: Matched weight loss was achieved in both arms. Body composition changes, reductions in alanine aminotransferase, liver steatosis, and disease activity were similar following both treatments. GLP-1RA treatment, but not lifestyle, improved glucose handling, fasting lipids, and significantly deceased DNL. The subcutaneous adipose transcriptome, circulating proteome profile and stool microbiome were not different between gr...