Screening for inflammatory markers identifies IL18-Rα as a potential link between exenatide and its anti-inflammatory effect. New results from the Combat-JUDO randomized controlled trial

Rasmus Stenlid, Sara Y Cerenius, Hannes Manell, Banu Küçükemre Aydin, Katharina Mörwald (Co-author), Julian Gomahr (Co-author), Marina Höghammar Mitkas, Ida Eriksson, Iris Ciba, Sabine Geiersberger (Co-author), David Thivel, Daniel Weghuber* (Co-author), Peter Bergsten, Anders Forslund

*Corresponding author for this work

Research output: Contribution to journalOriginal Articlepeer-review

Abstract

INTRODUCTION: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to treat obesity, with known anti-inflammatory properties. How the GLP-1RA exenatide effects inflammation in adolescents with obesity is not fully investigated.

METHODS: 44 patients were randomized to receive weekly subcutaneous injections with either 2 mg exenatide or placebo for 6 months. Plasma samples were collected at baseline and at the end of the study, and 90 inflammatory proteins were measured.

RESULTS: Following treatment with exenatide, 15 out of the 90 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL18-Rα was significantly lowered following treatment.

CONCLUSIONS: Weekly injections with 2 mg of exenatide lowers circulating IL18-Rα in adolescents with obesity, which may be a potential link between exenatide and its anti-inflammatory effect in vivo. This contributes to exenatide's pharmaceutical potential as a treatment for obesity beyond weight control and glucose tolerance, and should be further studied mechanistically.

Original languageEnglish
Number of pages12
JournalANNALS OF NUTRITION AND METABOLISM
DOIs
Publication statusE-pub ahead of print - 26 Oct 2023

Keywords

  • Glp-1
  • Il-18
  • IL-18R alpha
  • Inflammation
  • Obesity

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