Screening for Inflammatory Markers Identifies IL-18Rα as a Potential Link between Exenatide and Its Anti-Inflammatory Effect: New Results from the Combat-JUDO Randomized Controlled Trial

Ann Nutr Metab. 2023;79(6):522-527. doi: 10.1159/000534725. Epub 2023 Oct 26.

Abstract

Introduction: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, metabolic associated 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: Forty-four 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 92 inflammatory proteins were measured.

Results: Following treatment with exenatide, 15 out of the 92 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL-18Rα was significantly lowered following treatment.

Conclusions: Weekly injections with 2 mg of exenatide lowers circulating IL-18Rα 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.

Keywords: Glucagon-like peptide-1; IL-18; IL-18Rα; Inflammation; Obesity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Diabetes Mellitus, Type 2*
  • Exenatide / therapeutic use
  • Glucagon-Like Peptide-1 Receptor / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Inflammation / drug therapy
  • Martial Arts*
  • Pediatric Obesity* / complications
  • Peptides / therapeutic use
  • Venoms / therapeutic use

Substances

  • Exenatide
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Glucagon-Like Peptide-1 Receptor