Journal of Bioequivalence & Bioavailability

Abstract

Comparative Bioavailability Study of Rybelsus (Semaglutide) 3 mg Tablets of Novo Nordisk Versus Ozempic (Semaglutide) 2 mg/1.5 ml (1.34 mg/ml) Solution for Injection of Novo Nordisk under Fasting Condition in Healthy Subjects

Arjun Arumugam*, Geetha Lakshmi, Srinivas Gopineedu and Nageswara Rao

Background: The human GLP-1 receptor agonist, semaglutide, functions by binding to albumin, which is facilitated by modifying position 26 lysine with a hydrophilic spacer and a C18 fatty di-acid. In this study, Novo Nordisk's Ozempic (Semaglutide/1.5 mL (1.34 mg/mL) solution for injection and Rybelsus (Semaglutide) 14 mg tablets) were compared to determine the pharmacokinetic parameters of Semaglutide after oral and subcutaneous administration in healthy subjects. Through the Flash Glucose Monitoring System with a sensor, we evaluated the pharmacodynamic response of semaglutide the absorption of glucose into the blood when the drug was administered in two different routes, using Novo Nordisk's Semaglutide 3 mg tablets in healthy subjects. To evaluate pharmacokinetics of Semaglutide injection and tablet and to assess the applicability of an LCMS/MS quantification method.

Materials and methods: Dose and mode of administration, batch, expiry date, Ozempic (Semaglutide) 2 mg/1.5 mL (1.34 mg/mL) solution for injection, 0.37 mL × 1.34 mg (0.5 mg), subcutaneous injection in sitting posture under fasting condition, MP5E309, July, 2025. Dose and mode of administration, lot, expiry date, Rybelsus (Semaglutide) 3 mg tablets, 01 × 3 mg, oral with 240 ± 02 mL of water in sitting posture under fasting condition, MS6GG22, Feb, 2024. The 90% confidence intervals were evaluated for comparison and to evaluate the absolute bioavailability of C_max and AUC0-t. The 90% confidence intervals for C_max and AUC_0-t were 14.78%-58.01% and 4.51%-17.65% respectively.

Conclusion: The study was conducted as a proof-of-concept study to evaluate the pharmacokinetics of semaglutide when administered-subcutaneously and when administered as a tablet through the oral route. The pharmacokinetics obtained are similar to the reported values and when compared, the absolute bioavailability is about 1%-2% between these two products.

Published Date: 2024-12-09; Received Date: 2024-11-09