Assessing the effects of naltrexone‐bupropion on hepatic steatosis and fibrosis in patients with T2DM and overweight or obesity: Insights from a placebo‐controlled trial

作者：Alina Saidi, L Konings, Carmen A. W. Dietvorst, Vivian de Jong, Willem Pieter Brouwer, Aart‐Jan van der Lelij, Marco Alings, Martien van Wenum, Simone P. Rauh, Weiwei Xu, Manuel Castro Cabezas · 发表于：Diabetes Obesity and Metabolism · 年份：2025 · DOI：10.1111/dom.70071 · 被引用次数：1 · 研究领域：Liver Disease Diagnosis and Treatment、Alcohol Consumption and Health Effects、Drug-Induced Hepatotoxicity and Protection

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent among individuals with overweight or obesity and type 2 diabetes (T2DM), increasing the risk for liver-related and cardiovascular complications. Lifestyle changes to reduce body weight are the primary intervention to decrease the risk of MASLD and liver fibrosis. This study aimed to evaluate the impact of a pharmacological intervention with naltrexone/bupropion (NB) on hepatic steatosis and fibrosis risk in patients with T2DM using non-invasive tests. MATERIALS AND METHODS: In this post hoc analysis of a 56-week, randomized, double-blind, placebo-controlled trial 505 adults with T2DM and overweight or obesity were randomized to either NB or placebo (2:1), both combined with structured lifestyle counselling. Hepatic outcomes were measured using the Hepatic Steatosis Index (HSI), Metabolic Dysfunction-Associated Fibrosis-5 (MAF-5) and Fibrosis-4 (FIB-4) indices. Changes in liver-related indices were analysed by treatment arm and weight loss strata (<5%, ≥5%, ≥10%), and multivariable regression was used to identify predictors of hepatic improvement. RESULTS: At Week 56, the NB group achieved significantly greater body weight loss (-6.3 ± 7.2 kg vs. -2.5 ± 5.2 kg, p < 0.001). Lifestyle intervention with NB treatment compared with placebo significantly reduced HSI (-2.9 vs. -1.2, p < 0.001) and MAF-5 (-0.80 vs. -0.31, p = 0.003), while FIB-4 scores remained unchanged in both groups. The best ...