Semaglutide for the treatment of obesity: Results of two open randomized pharmacokinetic studies

Introduction. Obesity is a growing public health issue in Russia, increasing the risk of cardiovascular diseases, type 2 diabetes, and hypertension. Controlling obesity involves lifestyle changes and pharmacotherapy. Semaglutide, an effective obesity treatment, stimulates insulin production and reduces appetite. Developing a generic semaglutide preparation will improve its availability in Russia. Aim. To study the comparative pharmacokinetics, bioequivalence, safety and tolerability of semaglutide products GP40331 and Wegovy using concentrations of 0.68 and 3.2 mg/ml in healthy volunteers under fasting conditions. Materials and methods. Bioequivalence studies, conducted per Good Clinical Practice, were open-label, randomized, and involved healthy male volunteers. Subjects received semaglutide at single doses of 0.25 mg (0.68 mg/ml) and 0.5 mg (3.2 mg/ml) under fasting. Bioequivalence was determined by the 90% CI of the ratios of geometric mean values of the primary pharmacokinetic parameters (AUC0-t, Cmax). Semaglutide concentrations were measured using high-performance liquid chromatography with tandem mass spectrometry. Results. The 90% CI values for the ratios of geometric means of the primary PK parameters of semaglutide were 90.22–110.29 and 86.48–108.98% (0.68 mg/ml) and 90.62–115.71 and 92.86–113.51% (3.2 mg/ml). Comparable safety was proven for both concentrations. Conclusion. GP40331 and Wegovy at 0.68 and 3.2 mg/mL are bioequivalent and equally safe.