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

In vivo experimental study using Caenorhabditis elegans to examine neurobehavioral and physiological effects of semaglutide.

“Using Caenorhabditis elegans as a tractable model, we examined neurobehavioral and physiological effects of semaglutide, a long-acting GLP-1RA.”

Wild-type N2 Caenorhabditis elegans (nematodes).

“Wild-type N2 animals exposed to semaglutide (1 μM and 10 μM) showed significantly reduced chemotaxis toward the volatile odorant diacetyl.”

60-80 worms per data point for chemotaxis; progeny or eggs derived from a single worm for other assays.

“In panel A, each data point represents 60-80 worms, and in panels B–D, each data point represents the progeny or eggs derived from a single worm.”

Worms were maintained on experimental plates for 24 hours prior to assays; developmental staging was measured 48 to 72 hours after egg laying.

“Worms were maintained on these plates for 24 hours prior to behavioral and reproductive assays.”

Semaglutide exposure significantly reduced chemotaxis toward the odorant diacetyl at both tested concentrations.

“Both 1 μM and 10 μM semaglutide significantly suppressed chemotaxis relative to vehicle-treated controls.”

Semaglutide treatment reduced egg-laying and delayed larval development to the L4 stage.

“Semaglutide also reduced egg-laying and delayed larval development at both concentrations tested.”

Semaglutide treatment significantly increased the egg hatch rate compared to vehicle controls.

“Semaglutide treatment significantly increased egg hatching at both concentrations relative to vehicle-treated controls”

C. elegans lacks a canonical GLP-1 receptor ortholog, and high micromolar concentrations used may reflect non-specific stress or toxicity rather than specific receptor engagement.

“First, C. elegans lacks a canonical GLP-1 receptor ortholog, and the specific molecular target of semaglutide in this organism remains unidentified.”