Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
semaglutide | no change | area under the semaglutide plasma concentration-time curve from time zero to infinity (AUC) | people with hepatic impairment vs those with normal hepatic function | geometric mean ratios vs normal hepatic function: 1.11 (mild), 1.08 (moderate), 1.11 (severe) | exposure was similar | #1 |
semaglutide | no change | maximum semaglutide plasma concentration (Cmax) | people with hepatic impairment vs those with normal hepatic function | geometric mean ratios vs normal hepatic function: 1.11 (mild), 1.08 (moderate), 1.11 (severe) | exposure was similar | #2 |
semaglutide | no change | exposure | patients with hepatic impairment | - | did not appear to be affected | #3 |
semaglutide | no change | tolerability | participants with normal hepatic function or mild, moderate or severe hepatic impairment | - | was well tolerated | #4 |
semaglutide | no change | safety | participants with normal hepatic function or mild, moderate or severe hepatic impairment | - | there were no unexpected safety issues | #5 |
AIMS: To investigate whether the pharmacokinetic characteristics of semaglutide were altered in people with hepatic impairment, assessed using Child-Pugh criteria, vs those with normal hepatic function. METHODS: In this multicentre, open-label, parallel-group trial (sponsor Novo Nordisk, ClinicalTrials.gov ID NCT02210871), four groups of participants with normal hepatic function (n = 19) or mild (n = 8), moderate (n = 10) or severe (n = 7) hepatic impairment received a single, subcutaneous dose of 0.5 mg semaglutide. Semaglutide plasma concentrations were assessed frequently for 35 days after dosing. The primary endpoint was area under the semaglutide plasma concentration-time curve from time zero to infinity (AUC RESULTS: Semaglutide exposure was similar across all groups, with AUC CONCLUSIONS: Semaglutide exposure did not appear to be affected by hepatic impairment, suggesting that dose adjustment may not be necessary in patients with hepatic impairment. Semaglutide was well tolerated and there were no unexpected safety issues.