Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control.
obesity
GLP-1
GLP-1 receptor agonist
GLP-1 receptor analog
exenatide
glycemic control
pediatrics
treatment
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2023
2023
Historique:
received:
12
09
2023
accepted:
10
10
2023
medline:
1
12
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
epublish
Résumé
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. 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. 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. 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. clinicaltrials.gov, identifier NCT02794402.
Sections du résumé
Background
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
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
UNASSIGNED
clinicaltrials.gov, identifier NCT02794402.
Identifiants
pubmed: 38027106
doi: 10.3389/fendo.2023.1293093
pmc: PMC10646558
doi:
Substances chimiques
Exenatide
9P1872D4OL
Glucagon-Like Peptide 1
89750-14-1
Glucagon
9007-92-5
Proinsulin
9035-68-1
Glicentin
71567-77-6
Insulin
0
Glucose
IY9XDZ35W2
Banques de données
ClinicalTrials.gov
['NCT02794402']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1293093Informations de copyright
Copyright © 2023 Stenlid, Cerenius, Wen, Aydin, Manell, Chowdhury, Kristinsson, Ciba, Gjessing, Mörwald, Gomahr, Heu, Weghuber, Forslund and Bergsten.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from AstraZeneca. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
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