Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus.
The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D.



Subjects (18-64 years; body mass index 20.0-28.0 kg/m2; glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D.



The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D.



Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665.
Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
Julia K
JK
Mader
Division of Medicine and Science, Novo Nordisk A/S, Søborg, Denmark.
Lene
L
Jensen
Division of Medicine and Science, Novo Nordisk A/S, Søborg, Denmark.
Steen H
SH
Ingwersen
Division of Medicine and Science, Novo Nordisk A/S, Søborg, Denmark.
Erik
E
Christiansen
Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Sheffield, UK.
Simon
S
Heller
Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria. thomas.pieber@medunigraz.at.
Thomas R
TR
Pieber
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D000069450:Liraglutide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide