Pharmacokinetics, Safety, and Tolerability of Oral Semaglutide in Subjects With Hepatic Impairment

Semaglutide is a human glucagon-like peptide-1 analog that has been co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, for oral administration. This trial (NCT02016911) investigated whether hepatic impairment affects the pharmacokinetics, safety, and tolerability of oral semaglutide. Subjects were classified into groups: normal hepatic function (n=24), and mild (n=12), moderate (n=12), or severe (n=8) hepatic impairment according to Child-Pugh criteria, and received once-daily oral semaglutide (5mg for 5days followed by 10mg for 5days). Semaglutide plasma concentrations were measured during dosing and for up to 21days post-last dose. Area under the semaglutide plasma concentration-time curve from 0-24hours after the 10th dose (primary end point) and maximum semaglutide concentration after the 10th dose appeared similar across hepatic function groups. Similarly, there was no apparent effect of hepatic impairment on time to maximum semaglutide concentration (median range 1.0-1.5hours) or half-life (geometric mean range 142-156hours). No safety concerns were identified in subjects with hepatic impairment receiving semaglutide. Reported adverse events were in line with those observed for other glucagon-like peptide-1 receptor agonists. There was no apparent effect of hepatic impairment on the pharmacokinetics, safety, and tolerability of oral semaglutide. The results of this trial suggest that dose adjustment of oral semaglutide is not warranted in subjects with hepatic impairment.