Rybelsus

Semaglutide is a glucagon like peptide-1 (GLP 1) analogue with 94% sequence homology to human GLP 1. Semaglutide acts as a GLP-1 receptor agonist that binds to and activates the GLP 1 receptor, the target for native GLP 1. GLP 1 is a physiological hormone that has multiple actions in glucose and appetite regulation, and in the cardiovascular system. The glucose and appetite effects are specifically mediated via GLP 1 receptors in the pancreas and the brain. GLP 1 receptors are also expressed in the heart, vasculature and immune system and kidney from where it may mediate cardiovascular and microvascular effects. Compared to native GLP 1, semaglutide has a prolonged half-life of around one week. The principal mechanism of protraction is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilised against degradation by the dipeptidyl peptidase 4 (DPP 4) enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated, and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase. During hypoglycaemia semaglutide diminishes insulin secretion and does not impair glucagon secretion. Semaglutide reduces body weight and body fat mass through lowered energy intake, involving an overall reduced appetite, which includes increased satiety and reduced hunger, as well as improved control of eating and decreased food cravings. Insulin resistance is also reduced, probably through reduction in body weight. In addition, semaglutide reduces the preference for high fat foods. Semaglutide had a beneficial effect on plasma lipids, lowered systolic blood pressure and reduced inflammation in clinical studies. In animal studies, semaglutide attenuates the development of atherosclerosis by preventing aortic plaque progression and reducing inflammation in the plaque.