Semaglutide improves MASLD and MASH in people with HIV: The SLIM LIVER study.

OBJECTIVES: We have shown that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a highly effective therapy for metabolic dysfunction-associated steatotic liver disease (MASLD) in people with HIV (PWH). The OWLiver® metabolomics algorithms allow non-invasive MASLD severity staging without liver biopsy, but the use of metabolomic data for disease monitoring with GLP-1RA therapy has not been reported. METHODS: SLIM LIVER (ACTG A5371) was an open-label, phase 2b, single-arm trial of semaglutide in PWH and MASLD (2021-2022). Adult participants who showed clinical response (>2.27 kg weight loss) to semaglutide during the study (N = 36) had their serum analysed for metabolomic profiling by the OWLiver® panel. RESULTS: Twenty-four weeks of low-dose semaglutide led to significant improvement in MASLD disease severity by serum metabolomic profiling across all MASLD disease severity categories, suggesting histologic improvements. CONCLUSIONS: The OWLiver® metabolomics algorithms can be used to monitor MASLD severity during GLP-1RA therapy.