Six Months of Treatment with Bydureon® (Exenatide) Lowers 11 Inflammatory Biomarkers in Adolescents with Obesity

Background/Aims: Glucagon-like peptide 1 (GLP-1) delays gastric emptying and lowers appetite, which improves glucose homeostasis and leads to reduced body weight. The CombatJUDO study was a six-month, double-blind, multi-center randomized controlled trial performed between September 2015 and September 2016 in Uppsala, Sweden and Salzburg, Austria. Participants (aged 10-18, n = 88) with obesity were recruited and randomly assigned to receive weekly injections of either 2mg of the GLP-1 receptor agonist (GLP-1RA) exenatide (Bydureon®, AstraZeneca) or placebo. The study found that Bydureon® was well tolerated and led to a reduction of BMI-SDS. Obesity is associated with low-grade chronic inflammation in multiple tissues. Treatment with GLP-1RA has been shown to reduce inflammation in e.g., type 2 diabetes, vascular disease, and non-alcoholic steatohepatitis. However, the effects of exenatide on inflammation in pediatric obesity have not been fully investigated. Our aim was to determine if the GLP-1RA exenatide affects inflammation in adolescent obesity. Methods: Blood was collected in EDTA tubes after 10h of fasting from all participants in the Swedish arm of the Combat-JUDO study. Relative concentrations of 92 proteins associated with inflammation were measured by PEA (Proseek Multiplex Inflammation I, Olink Bioscience, Uppsala). Intention-to-treat (ITT) and Last Observation Carried Forward approaches were used for all data analysis. Results: Of the 44 participants, 22 received exenatide treatment (9 males, 13 females, mean age 14.55, mean BMI-SDS 3.12), and 22 received placebo (13 males, 9 females, mean age 13.55, mean BMI-SDS 3.28). 37 participants completed the study. Of the 92 inflammatory markers, 12 showed significant change in concentration following exenatide treatment compared to placebo: IL18R1, TRAIL, CXCL5, CD40, OPG, CX3CL1, CD244, LAPTGFβ1, CXCL1, LIFR, IL10, and CCL4. All except IL10 decreased in concentration. IL10 increased significantly more in the placebo group compared to treatment. IL-1β, TNF-α and IFN-γ were excluded due to plasma concentrations below limit of detection. Conclusion: In conclusion, weekly injections of 2mg Bydureon® lowers inflammatory biomarkers in adolescent obesity.