Effects of semaglutide on vessel morphology: Studies on the chicken chorioallantoic membrane

Glucagon-Like Peptide-1 (GLP-1) receptor agonists are widely used to manage type 2 diabetes and promote weight loss. Semaglutide (SEM)-a long acting GLP-1-has experienced an extraordinary surge in popularity since its approval in 2017. Between 2021 and 2023, SEM prescription fills in the U.S. climbed to 2.56 million per month. Yet, the uptake of SEM into larger populations has raised safety concerns, with provocative findings now suggesting that SEM could negatively affect ocular and reproductive systems, counter to its beneficial effects on the heart. At least some of these concerns involve SEMs ability to alter vascular morphology in these organs. Herein, we study the impact of SEM on vasculature using the well-established chicken chorioallantoic membrane (CAM). This in vivo model mimics vascular beds found in the human eye and placenta and can approximate the effects of drugs on these organs. The CAM also responds to vasoactive drugs in a similar way to the coronary arteries of the heart. Hence, the CAM provides a convenient system to simultaneously interrogate the impact of SEM on ocular, reproductive, and coronary vascular biology. Our studies show that SEM causes vessels to develop with fewer branching points, yielding longer and more direct connections, that shift local blow flow patterns. However, these changes are only significant at SEM concentrations well above the therapeutic dose.