Carmen A.W. Dietvorst1,2, Willem Pieter Brouwer3, Diederick E. Grobbee4,5, Marco Alings6, Maja Thiele7,8, Jose M. Ordovas9, Kirsten A.C. Berk2, Robin P. Peeters10, Manuel Castro Cabezas1,5,10
1 Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
2 Department of Internal Medicine, Division of Dietetics, Erasmus MC, Rotterdam, The Netherlands
3 Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
4 University Medical Center, Utrecht, The Netherlands
5 Julius Clinical, Zeist, The Netherlands
6 Department of Cardiology, Amphia hospital, Breda, The Netherlands
7 Center for Liver Research, Odense University Hospital, Odense, Denmark
8 Evido Health, Copenhagen, Denmark
9 USDA Human Nutrition Research Center on Aging, Tufts University, Boston, United States
10 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to overweight and obesity. Lifestyle modification is the cornerstone of therapy, but long-term weight reduction is challenging. Pharmacological agents such as naltrexone/bupropion (NB) may enhance weight loss and improve liver health.
Aim: This study examined the impact of a 56‑week lifestyle program with or without NB on hepatic markers and their association with weight change.
Methods: The COR‑BMOD trial enrolled adults with obesity or overweight plus hypertension or dyslipidaemia into a 56‑week randomised, double‑blind study combining an intensive lifestyle intervention with either placebo (LS) or NB in a 1:3 ratio. The program consisted of an energy-restricted diet (1200-1500 kcal/day), exercise guidance, and 28 group sessions targeting behavioural change. Weight, BMI, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Hepatic Steatosis Index (HSI) and Metabolic Associated Fibrosis Score‑5 (MAF-5) were assessed at baseline and after 56 weeks. (Non) parametric tests and regression analyses were performed.
Results: A total of 460 patients completed the study (mean age 46.8 ± 10.4 years; mean BMI 32.5 ± 5.0 kg/m²; 88% female; LS n=118, NB n=342). After 56 weeks, both groups showed significant improvements in weight (LS −7.9, NB −11.7 kg; p<0.001 for each), BMI (LS −2.8, NB −4.7 kg/m²; p<0.001), ALT (LS −2.2 U/L, NB −2.8 U/L; p<0.05), AST (LS −1.9 U/L, NB −1.5 U/L; p<0.05), HSI (LS −3.5, NB −4.6; p<0.001), and MAF‑5 (LS −1.1, NB −1.2; p<0.001). Improvements in BMI and HSI were significantly greater in the NB group compared with LS (p<0.05). Regression analyses showed a moderate correlation between weight change and ALT in both groups. Weight loss was also strongly correlated with a decrease of MAF‑5 and HSI.
Conclusions: NB treatment produced greater weight loss than lifestyle modification alone, with a more pronounced impact on liver steatosis than on liver fibrosis. These findings support NB as an effective adjunct to lifestyle intervention in overweight‑related MASLD. The results reinforce that weight reduction remains the key determinant of improved liver health.