Incretin / GLP-1
FDA Approved
Semaglutide
Also known as: NN9535
Long-acting GLP-1 receptor agonist. Studied in metabolic and glycaemic regulation research.
Research overview
Semaglutide (development code NN9535; licensed medicines) is a synthetic analogue of glucagon-like peptide-1 (GLP-1), a hormone the gut releases after eating. Novo Nordisk developed it after liraglutide: it differs from human GLP-1 at two positions and carries a fatty acid chain, changes designed to resist breakdown and to bind albumin in the blood, so it lasts much longer than natural GLP-1 (Lau et al., J Med Chem 2015). It is licensed in the UK, EU and US as a medicine for type 2 diabetes and for weight management alongside diet and exercise. These licences rest on large randomised trials, including the SUSTAIN trials in type 2 diabetes and the STEP trials in obesity. In the US is also licensed for some adults with heart disease and overweight or obesity, based on the SELECT trial in 17,604 people (Lincoff et al., NEJM 2023).
Most of what is known about how it acts on appetite circuits in the brain comes from rat and mouse studies (Gabery et al., 2020). The research material supplied here is not the licensed medicine. Supplied for laboratory research use only.
Mechanism of action
Semaglutide binds and activates the GLP-1 receptor, a G-protein coupled receptor found on the insulin-making beta cells of the pancreas and in the gut and brain. In the pancreas this increases insulin release when blood glucose is high and lowers glucagon release, and GLP-1 receptor signalling also slows stomach emptying. In rats and mice, semaglutide did not cross the blood-brain barrier but reached brain areas next to it, such as the area postrema, and activated nerve cells in several regions linked to food intake (Gabery et al., 2020).