title: Transfer of liraglutide from blood to cerebrospinal fluid is minimal in patients with type 2 diabetes.
abstract: Treatment with liraglutide leads to weight loss. We investigated whether blood-to-cerebrospinal fluid (CSF) transfer of liraglutide occurs, and if so, whether it associates with clinical weight loss following liraglutide treatment in humans. We performed lumbar puncture and blood sampling in eight patients with type 2 diabetes (mean (range)): age 63 (54-79) years; actual body weight: 90 (75-118) kg treated with 1.8 mg liraglutide for 14 (5-22) months and with a treatment-induced weight loss of 8.4 (7-11) kg. We measured liraglutide in plasma and CSF with a radioimmunoassay specific for the N-terminus of the GLP-1 moiety of liraglutide. Mean plasma liraglutide was 31 (range: 21-63) nmol l(-1). The mean CSF-liraglutide concentration was 6.5 (range: 0.9-13.9) pmol l(-1). Ratio of CSF: plasma-liraglutide concentrations was 0.02 (range: 0.07-0.002)% and plasma liraglutide did not correlate with CSF-liraglutide levels (P=0.67). Body weight loss tended to correlate with plasma-liraglutide levels (P=0.06), but not with CSF-liraglutide levels (P=0.69). In conclusion, we measured very low concentrations of liraglutide in CSF, and the levels of CSF liraglutide did not correlate with the actual clinical weight loss in these patients. The amount of liraglutide in plasma tended to correlate with the clinical weight loss.
authors.affiliation: Department of Medicine, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Christensen
authors.affiliation: Department of Medicine, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A H
authors.initials: AH
authors.lastname: Sparre-Ulrich
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Anaesthesiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: U
authors.initials: U
authors.lastname: Grevstad
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M M
authors.initials: MM
authors.lastname: Rosenkilde
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Medicine, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Department of Medicine, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000368:Aged; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D019440:Anti-Obesity Agents; D015415:Biomarkers; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1