Pharmacokinetic Characteristics of a Once-Weekly Combination Therapy of Insulin Icodec and Semaglutide Versus Its Separate Components in Chinese Individuals with Type 2 Diabetes.

INTRODUCTION: IcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide 1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type 2 diabetes (T2D). METHODS: In a randomized, double-blind, three-period crossover study, 20 Chinese individuals with T2D (18-64 years, body mass index 18.5-34.9 kg/m, glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6-9 weeks. Blood was drawn for pharmacokinetic measurement until 840 h post dose. RESULTS: Combining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC) and 1.02 [0.96;1.09] for maximum concentration (C), i.e., within the bioequivalence acceptance interval of 0.80-1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC(IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide Cwas higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66 h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product. CONCLUSION: In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05435677.