Ozempic(semaglutide)

Ozempic (semaglutide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease, and to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes mellitus and chronic kidney disease. The approved maintenance doses are 0.5 mg and 1.0 mg.

Semaglutide demonstrates a mean half-life of 155 hours in subjects with type 2 diabetes. It acts as a GLP-1 receptor agonist with a potency of 0.15 nM. In male diabetic db/db mice, semaglutide showed an ED50 for lowering blood glucose (6 hours post dosing) of 1.2 µg/kg, and was 20-fold higher in relative potency compared to liraglutide for blood glucose lowering in the same model. Maximal effect on blood glucose lowering in these mice was observed at doses of 4-8 µg/kg over a 4-week study.

Safety evaluations included a rat CNS study where pharmacological effects were observed at 95 µg/kg, representing a 1.5-fold exposure multiple relative to the human maximum recommended human dose (MRHD) Cmax of ~32 nM. A NOAEL of 22 µg/kg was established in this study. In cynomolgus monkeys, no clinically relevant cardiovascular findings were observed at 470 µg/kg, which corresponds to a 14-fold exposure multiple relative to MRHD Cmax.