Abstract
Semaglutide has beneficial effects on glycaemic control and produces clinically meaningful weight loss in people with type 2 diabetes and obesity, in part by central appetite suppression effects. The effects of GLP-1 receptor activation on hypothalamic, brainstem and reward-related neural circuits and its potential role in long-term metabolic regulation were explored. Mechanism oriented rapid review and comparative analyses of RCTs were performed, along with extension studies and relevant neurobiological research. The results suggest that semaglutide decreases hunger, food craving and energy intake, but enhances satiety and eating behavior control. Clinical trials also show that after continuous therapy, body weight and glycated haemoglobin levels are reduced over time. But significant weight gain following withdrawal of the medication indicates that the central anorexigenic effects are primarily sustained during drug treatment. It is important to consider semaglutide as a long-term treatment option for achieving and maintaining durable metabolic control, and not as a treatment that has been shown to facilitate medication-free diabetes remission. While additional research is required to identify which individuals will maintain these effects following the completion of semaglutide treatment, central control of appetite seems to be a crucial pathway between treatment, weight loss and metabolic improvement.