title: Preserved pharmacokinetic exposure and distinct glycemic effects of insulin degludec and liraglutide in IDegLira, a fixed-ratio combination therapy.
abstract: Insulin degludec/liraglutide (IDegLira) is a novel fixed-ratio combination of the basal insulin insulin degludec (IDeg) and liraglutide, a glucagon-like peptide-1 analog. The pharmacokinetics (PK) and pharmacodynamics of IDegLira were assessed versus its components. A single-dose, randomized, 4-period crossover clinical pharmacology study in healthy subjects compared the bioavailability of IDegLira with its monocomponents. Dose proportionality, covariate effects on exposure, and exposure-response for change in glycated hemoglobin were analyzed based on data from a randomized treat-to-target phase 3 study in subjects with type 2 diabetes. Overall, the PK properties of IDeg and liraglutide were preserved for IDegLira. Liraglutide exposure was lower when dosed as IDegLira but met the criterion for equivalence. No relevant deviations from dose proportionality for the IDegLira components were observed. Covariate effects on exposure were consistent with previous results. Glycemic response to IDegLira was larger than with IDeg or liraglutide alone, reflecting their distinct glucose-lowering effects throughout the dose/exposure range.
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
authors.affiliation: Atlanta Diabetes Associates, Atlanta, GA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
authors.affiliation: Global Development, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Steen Hvass
authors.initials: SH
authors.lastname: Ingwersen
authors.affiliation: Global Development, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Lisbeth Vestergård
authors.initials: LV
authors.lastname: Jacobsen
authors.affiliation: Global Development, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Poulsen
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D000069450:Liraglutide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069450:Liraglutide; C000613158:IDegLira; C571886:insulin degludec
keywords: Clinical Pharmacology (CPH); Drug Interactions; Endocrinology (END); Exposure-Response; Pharmacodynamics (PDY); Population Pharmacokinetics