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

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-R alpha was significantly lowered following treatment.Conclusions: Weekly injections with 2 mg of exenatide lowers circulating IL18-R alpha 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.