title: Treatment with liraglutide--a once-daily GLP-1 analog--does not reduce the bioavailability of ethinyl estradiol/levonorgestrel taken as an oral combination contraceptive drug.
abstract: Liraglutide is a once-daily human GLP-1 analog for treatment of type 2 diabetes. Like other GLP-1 analogs, liraglutide delays gastric emptying, which could potentially affect absorption of concomitantly administered oral drugs. This study investigated the effect of liraglutide on the pharmacokinetics of the components of an oral contraceptive (ethinyl estradiol/levonorgestrel). Postmeno-pausal healthy women (n = 21) were included. A single dose of this contraceptive was administered. Blood samples for ethinyl estradiol/levonorgestrel measurements were drawn until 74 hours post dosing of the contraceptive during liraglutide and placebo treatments. The 90% confidence interval (CI) of the ratio of the area under the curve (AUC) (1.06; 90% CI, 0.99-1.13) for ethinyl estradiol (during liraglutide and placebo) was within defined limits, demonstrating equivalence. The 90% CI for the ratio of AUC for levonorgestrel was not fully contained within the limits (1.18; 90% CI, 1.04-1.34) (levonorgestrel AUC was 18% greater with liraglutide vs placebo). However, equivalence was demonstrated for levonorgestrel AUC(0-t) (1.15; 90% CI, 1.06-1.24). Equivalence was not demonstrated for maximum concentration (C(max)); values for ethinyl estradiol and levonorgestrel C(max) were 12% and 13% lower with liraglutide versus placebo, respectively. Both reached C(max) ~1.5 hours later with liraglutide. No clinically relevant reduction in bioavailability of ethinyl estradiol/levonorgestrel occurred.
authors.affiliation: Novo Nordisk A/S, Vandtårnsvej 108-110, 2860 Søborg, Denmark. lvj@novonordisk.com
authors.forename: Lisbeth V
authors.initials: LV
authors.lastname: Jacobsen
authors.forename: Jan
authors.initials: J
authors.lastname: Vouis
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hindsberger
authors.forename: Milan
authors.initials: M
authors.lastname: Zdravkovic
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016912:Levonorgestrel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000069450:Liraglutide; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D007004:Hypoglycemic Agents; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1