Semaglutide Reduces Odorant-Driven Chemotaxis and Reproductive Output in Caenorhabditis elegans

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce food intake and body weight in humans, partly via neural circuits governing reward and energy homeostasis. Using Caenorhabditis elegans as a tractable model, we examined neurobehavioral and physiological effects of semaglutide, a long-acting GLP-1RA. Wild-type N2 animals exposed to semaglutide (1 μM and 10 μM) showed significantly reduced chemotaxis toward the volatile odorant diacetyl. Semaglutide also reduced egg-laying and delayed larval development at both concentrations tested. These phenotypes demonstrate that semaglutide alters multiple C. elegans behaviors and developmental processes, supporting its utility as a model system for investigating GLP-1RA mechanisms at cellular resolution.