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Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control

BACKGROUND: GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat adolescent obesity. However, the effect on endogenous GLP-1 secretory patterns following treatment in adolescents is unknown. The GLP-1RA exenatide was shown to significantly lower BMI and 2-hour glucose in adolescents with...

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Autores principales: Stenlid, Rasmus, Cerenius, Sara Y., Wen, Quan, Aydin, Banu Küçükemre, Manell, Hannes, Chowdhury, Azazul, Kristinsson, Hjalti, Ciba, Iris, Gjessing, Erik S., Mörwald, Katharina, Gomahr, Julian, Heu, Verena, Weghuber, Daniel, Forslund, Anders, Bergsten, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646558/
https://www.ncbi.nlm.nih.gov/pubmed/38027106
http://dx.doi.org/10.3389/fendo.2023.1293093
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author Stenlid, Rasmus
Cerenius, Sara Y.
Wen, Quan
Aydin, Banu Küçükemre
Manell, Hannes
Chowdhury, Azazul
Kristinsson, Hjalti
Ciba, Iris
Gjessing, Erik S.
Mörwald, Katharina
Gomahr, Julian
Heu, Verena
Weghuber, Daniel
Forslund, Anders
Bergsten, Peter
author_facet Stenlid, Rasmus
Cerenius, Sara Y.
Wen, Quan
Aydin, Banu Küçükemre
Manell, Hannes
Chowdhury, Azazul
Kristinsson, Hjalti
Ciba, Iris
Gjessing, Erik S.
Mörwald, Katharina
Gomahr, Julian
Heu, Verena
Weghuber, Daniel
Forslund, Anders
Bergsten, Peter
author_sort Stenlid, Rasmus
collection PubMed
description BACKGROUND: GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat adolescent obesity. However, the effect on endogenous GLP-1 secretory patterns following treatment in adolescents is unknown. The GLP-1RA exenatide was shown to significantly lower BMI and 2-hour glucose in adolescents with obesity, in the placebo-controlled, randomized controlled trial Combat-JUDO. The aim of this study was to evaluate effects of weekly injections of 2 mg exenatide extended release on secretory patterns of endogenous hormones during OGTT. SUBJECTS AND MEASUREMENTS: This study was a pre-planned sub-study of the Combat-JUDO trial, set at the Pediatric clinic at Uppsala University Hospital, Sweden and Paracelsus Medical University, Austria. 44 adolescents with obesity were included and randomized 1:1 to treatment:placebo. 19 patients in the treatment group and 18 in the placebo group completed the trial. Before and after treatment, GLP-1, glucose, insulin, glucagon and glicentin levels were measured during OGTT; DPP-4 and proinsulin were measured at fasting. A per-protocol approach was used in the analyses. RESULTS: Exenatide treatment did not affect GLP-1 levels during OGTT. Treatment significantly lowered DPP-4, proinsulin and the proinsulin-to-insulin ratio at fasting, increased glicentin levels but did not affect insulin, C-peptide or glucagon levels during OGTT. CONCLUSION: Weekly s.c. injections with 2 mg of exenatide maintains endogenous total GLP-1 levels and lowers circulating DPP-4 levels. This adds an argument in favor of using exenatide in the treatment of pediatric obesity. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT02794402
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spelling pubmed-106465582023-01-01 Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control Stenlid, Rasmus Cerenius, Sara Y. Wen, Quan Aydin, Banu Küçükemre Manell, Hannes Chowdhury, Azazul Kristinsson, Hjalti Ciba, Iris Gjessing, Erik S. Mörwald, Katharina Gomahr, Julian Heu, Verena Weghuber, Daniel Forslund, Anders Bergsten, Peter Front Endocrinol (Lausanne) Endocrinology BACKGROUND: GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat adolescent obesity. However, the effect on endogenous GLP-1 secretory patterns following treatment in adolescents is unknown. The GLP-1RA exenatide was shown to significantly lower BMI and 2-hour glucose in adolescents with obesity, in the placebo-controlled, randomized controlled trial Combat-JUDO. The aim of this study was to evaluate effects of weekly injections of 2 mg exenatide extended release on secretory patterns of endogenous hormones during OGTT. SUBJECTS AND MEASUREMENTS: This study was a pre-planned sub-study of the Combat-JUDO trial, set at the Pediatric clinic at Uppsala University Hospital, Sweden and Paracelsus Medical University, Austria. 44 adolescents with obesity were included and randomized 1:1 to treatment:placebo. 19 patients in the treatment group and 18 in the placebo group completed the trial. Before and after treatment, GLP-1, glucose, insulin, glucagon and glicentin levels were measured during OGTT; DPP-4 and proinsulin were measured at fasting. A per-protocol approach was used in the analyses. RESULTS: Exenatide treatment did not affect GLP-1 levels during OGTT. Treatment significantly lowered DPP-4, proinsulin and the proinsulin-to-insulin ratio at fasting, increased glicentin levels but did not affect insulin, C-peptide or glucagon levels during OGTT. CONCLUSION: Weekly s.c. injections with 2 mg of exenatide maintains endogenous total GLP-1 levels and lowers circulating DPP-4 levels. This adds an argument in favor of using exenatide in the treatment of pediatric obesity. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT02794402 Frontiers Media S.A. 2023-11-01 /pmc/articles/PMC10646558/ /pubmed/38027106 http://dx.doi.org/10.3389/fendo.2023.1293093 Text en Copyright © 2023 Stenlid, Cerenius, Wen, Aydin, Manell, Chowdhury, Kristinsson, Ciba, Gjessing, Mörwald, Gomahr, Heu, Weghuber, Forslund and Bergsten https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Stenlid, Rasmus
Cerenius, Sara Y.
Wen, Quan
Aydin, Banu Küçükemre
Manell, Hannes
Chowdhury, Azazul
Kristinsson, Hjalti
Ciba, Iris
Gjessing, Erik S.
Mörwald, Katharina
Gomahr, Julian
Heu, Verena
Weghuber, Daniel
Forslund, Anders
Bergsten, Peter
Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control
title Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control
title_full Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control
title_fullStr Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control
title_full_unstemmed Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control
title_short Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control
title_sort adolescents with obesity treated with exenatide maintain endogenous glp-1, reduce dpp-4, and improve glycemic control
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646558/
https://www.ncbi.nlm.nih.gov/pubmed/38027106
http://dx.doi.org/10.3389/fendo.2023.1293093
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