Document Type

Presentation

Publication Date

Fall 10-5-2026

Abstract

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist widely used to treat type 2 diabetes and obesity. Because many patients taking semaglutide also use other medications, understanding its potential effects on drug metabolism is important. Hepatic cytochrome P450 (CYP450) enzymes metabolize many commonly used medications, and changes in their expression may alter drug levels and treatment response. However, the effects of semaglutide on hepatic CYP450 expression remain poorly understood.: To determine whether semaglutide alters hepatic CYP450 enzyme expression and establish a human liver cell model for studying its potential effects on drug metabolism. Publicly available mouse gene expression data (GEO GSE243681) were analyzed to identify CYP450 genes altered following semaglutide treatment. Candidate genes will be experimentally validated in differentiated HepaRG human liver cells treated with vehicle, rifampicin, or semaglutide. Rifampicin will serve as a positive control for CYP450 induction. Changes in selected CYP450 genes will be measured using quantitative PCR, followed by RNA sequencing to assess broader gene expression changes.: Preliminary analysis identified several CYP450 genes with altered expression following semaglutide treatment in mice, suggesting potential effects on hepatic drug metabolism. HepaRG cells are currently being established and optimized for experimental validation. This study will determine whether semaglutide alters CYP450 expression in a human liver cell model and identify potential implications for the metabolism of commonly used medications. Understanding these effects may help inform medication management and monitoring of potential drug interactions in patients receiving semaglutide, particularly those taking multiple medications.

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