O043 - TREATMENT WITH NALTREXONE/BUPROPION ENHANCES LIFESTYLE-INDUCED IMPROVEMENTS IN HEPATIC STEATOSIS IN ADULTS WITH OVERWEIGHT/OBESITY

O043

TREATMENT WITH NALTREXONE/BUPROPION ENHANCES LIFESTYLE-INDUCED IMPROVEMENTS IN HEPATIC STEATOSIS IN ADULTS WITH OVERWEIGHT/OBESITY

C. A. Dietvorst^1,2,*, W. P. Brouwer³, D. E. Grobbee^4,5, M. Alings⁶, M. Thiele⁷, J. M. Ordovas⁸, K. A. Berk², R. P. Peeters², M. Castro Cabezas^1,2,4

¹Internal Medicine, Franciscus, ²Internal Medicine, ³Gastroenterology and Hepatology, Erasmus MC, Rotterdam, ⁴Julius Clinical, Zeist, ⁵Julius Centre for Health Sciences and Primary Care, Utrecht, ⁶Cardiology, Amphia, Breda, Netherlands, ⁷Center for Liver Research, Odense University Hospital, Odense, Denmark, ⁸USDA Human Nutrition Research Center on Aging, Tufts University, Boston, United States

Rationale: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to overweight. Although lifestyle modification is the primary treatment, pharmacological interventions such as naltrexone/bupropion (NB) may also induce weight loss and thereby improve liver health. 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 overweight/obesity 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 behavioural change sessions. Weight, BMI, ALT, AST, Hepatic Steatosis Index (HSI) and Metabolic Associated Fibrosis Score‑5 (MAF-5) were assessed at baseline and after 56 weeks.

Results: 460 patients completed the study (age 46.8 ± 10.4 years; 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). Weight loss was strongly correlated with a decrease of MAF‑5 and HSI.

Conclusion: NB treatment produced greater weight loss than lifestyle modification alone, with a more pronounced impact on liver steatosis. 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.

Disclosure of Interest: None declared