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Transfer of liraglutide from blood to cerebrospinal fluid is minimal in patients with type 2 diabetes

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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.

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Acknowledgements

We are grateful to the participating patients and acknowledge the skillful laboratory assistance from I. A. Mandir at Department of Clinical Biochemistry, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark, J. Purtoft, N. Kjeldsen and S. M. Schmidt from Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark, and S. P. Olesen and L. Albæk from Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Author contributions

MC, JJH and FKK designed the study. MC and TV recruited the participants. MC and UG performed the clinical experiments. AHSU and BH analyzed the blood and CSF samples. All authors contributed to the interpretation of the data and the editing and approval of the manuscript. MC is the guarantor of this work.

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Authors and Affiliations

  1. Department of Medicine, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

    M Christensen, A H Sparre-Ulrich, T Vilsbøll & F K Knop

  2. Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark

    M Christensen

  3. Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    A H Sparre-Ulrich & M M Rosenkilde

  4. NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    B Hartmann, J J Holst & F K Knop

  5. Department of Anaesthesiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

    U Grevstad

Authors
  1. M Christensen
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  2. A H Sparre-Ulrich
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  3. B Hartmann
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  4. U Grevstad
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  5. M M Rosenkilde
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  6. J J Holst
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  7. T Vilsbøll
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  8. F K Knop
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Corresponding author

Correspondence to M Christensen.

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Competing interests

JJH has served as a consultant or advisor to: Novartis Pharmaceuticals, Novo Nordisk, Merck, Sharp and Dome and Roche. JJH has received fees for speaking from Novo Nordisk, Merck, Sharp and Dome and GSK. TV has received fees for consulting, lecturing and/or being part of an advisory board from: AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, GI Dynamics, Merck Sharp & Dohme, Novo Nordisk, Novartis, Sanofi, Takeda and Zealand Pharma. TV has received research support from Novo Nordisk. FKK has received fees for consulting, lecturing and/or being part of an advisory board from: AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, Gilead Sciences, Merck Sharp & Dohme, Novartis, Novo Nordisk, Ono Pharmaceuticals, Sanofi, Zealand Pharma. FKK has received research support from Sanofi and Novo Nordisk. The remaining authors declare no conflicts of interest.

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Christensen, M., Sparre-Ulrich, A., Hartmann, B. et al. Transfer of liraglutide from blood to cerebrospinal fluid is minimal in patients with type 2 diabetes. Int J Obes 39, 1651–1654 (2015). https://doi.org/10.1038/ijo.2015.136

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  • DOI: https://doi.org/10.1038/ijo.2015.136

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