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Randomised comparison of intravenous and subcutaneous routes of glucagon-like peptide-1 administration for lowering plasma glucose in hyperglycaemic subjects with type 2 diabetes

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dc.contributor.authorQuast, D.R.
dc.contributor.authorLancaster, D.
dc.contributor.authorXie, C.
dc.contributor.authorBound, M.J.
dc.contributor.authorGrivell, J.
dc.contributor.authorJones, K.L.
dc.contributor.authorHorowitz, M.
dc.contributor.authorMeier, J.J.
dc.contributor.authorWu, T.
dc.contributor.authorRayner, C.K.
dc.contributor.authorNauck, M.A.
dc.date.issued2024
dc.descriptionData source: Supporting information, https://doi.org/10.1111/dom.15736
dc.description.abstractAim: To perform a direct, double-blind, randomised, crossover comparison of subcutaneous and intravenous glucagon-like peptide-1 (GLP-1) in hyperglycaemic subjects with type 2 diabetes naïve to GLP-1-based therapy. Materials and Methods: Ten fasted, hyperglycaemic subjects (1 female, age 63 ± 10 years [mean ± SD], glycated haemoglobin 73.5 ± 22.0 mmol/mol [8.9% ± 2.0%], both mean ± SD) received subcutaneous GLP-1 and intravenous saline, or intravenous GLP-1 and subcutaneous saline. Infusion rates were doubled every 120 min (1.2, 2.4, 4.8 and 9.6 pmol kg1 min1 for subcutaneous, and 0.3, 0.6, 1.2 and 2.4 pmol kg1 min1 for intravenous). Plasma glucose, total and intact GLP-1, insulin, C-peptide, glucagon and gastrointestinal symptoms were evaluated over 8 h. The results are presented as mean ± SEM. Results: Plasma glucose decreased more with intravenous (by 8.0 mmol/L [144 mg/dL]) than subcutaneous GLP-1 (by 5.6 mmol/L [100 mg/dL]; p < 0.001). Plasma GLP-1 increased dose-dependently, but more with intravenous than subcutaneous for both total (Δmax 154.2 ± 3.9 pmol/L vs. 85.1 ± 3.8 pmol/L; p < 0.001), and intact GLP-1 (Δmax 44.2 ± 2.2 pmol/L vs. 12.8 ± 2.2 pmol/L; p < 0.001). Total and intact GLP-1 clearance was higher for subcutaneous than intravenous GLP-1 (p < 0.001 and p = 0.002, respectively). The increase in insulin secretion was greater, and glucagon was suppressed more with intravenous GLP-1 (p < 0.05 each). Gastrointestinal symptoms did not differ (p > 0.05 each). Conclusions: Subcutaneous GLP-1 administration is much less efficient than intravenous GLP-1 in lowering fasting plasma glucose, with less stimulation of insulin and suppression of glucagon, and much less bioavailability, even at fourfold higher infusion rates.
dc.description.statementofresponsibilityDaniel R. Quast, Dara Lancaster, Cong Xie, Michelle J. Bound, Jacqueline Grivell, Karen L. Jones, Michael Horowitz, Juris J. Meier, Tongzhi Wu, Christopher K. Rayner, Michael A. Nauck
dc.identifier.citationDiabetes, Obesity and Metabolism, 2024; 26(9):3897-3905
dc.identifier.doi10.1111/dom.15736
dc.identifier.issn1462-8902
dc.identifier.issn1462-8902
dc.identifier.orcidXie, C. [0000-0002-0054-9269]
dc.identifier.orcidBound, M.J. [0000-0003-0211-5832]
dc.identifier.orcidJones, K.L. [0000-0002-1155-5816]
dc.identifier.orcidHorowitz, M. [0000-0002-0942-0306]
dc.identifier.orcidWu, T. [0000-0003-1656-9210]
dc.identifier.orcidRayner, C.K. [0000-0002-5527-256X]
dc.identifier.urihttps://hdl.handle.net/2440/142985
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT176023
dc.rights© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttp://dx.doi.org/10.1111/dom.15736
dc.subjectclinical physiology
dc.subjecteffectiveness
dc.subjectGLP‐1
dc.subjectincretin physiology
dc.subjectrandomised trial
dc.subjecttype 2 diabetes
dc.subject.meshHumans
dc.subject.meshDiabetes Mellitus, Type 2
dc.subject.meshHyperglycemia
dc.subject.meshGlucagon
dc.subject.meshInsulin
dc.subject.meshC-Peptide
dc.subject.meshBlood Glucose
dc.subject.meshHypoglycemic Agents
dc.subject.meshInfusions, Intravenous
dc.subject.meshInjections, Subcutaneous
dc.subject.meshCross-Over Studies
dc.subject.meshDouble-Blind Method
dc.subject.meshAged
dc.subject.meshMiddle Aged
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshGlucagon-Like Peptide 1
dc.subject.meshGlycated Hemoglobin
dc.titleRandomised comparison of intravenous and subcutaneous routes of glucagon-like peptide-1 administration for lowering plasma glucose in hyperglycaemic subjects with type 2 diabetes
dc.typeJournal article
pubs.publication-statusPublished

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