Change in circulating irisin level and its association with lipid metabolism after exenatide treatment in patients with type 2 diabetes mellitus

Background Irisin is a metabolism-related myokine associated with lipid metabolism and insulin resistance. However, its changes during glucagon-like peptide-1 (GLP-1) receptor agonist therapy remain unclear. Methods This exploratory analysis of a multicenter trial included 189 adults with T2DM inadequately controlled with metformin and/or insulin secretagogue. The participants received the GLP-1 receptor agonist exenatide as an add-on therapy for 16 weeks. Serum irisin and glycolipid metabolism were evaluated. Comparison was performed between two subgroups of the participants stratified by a median change from baseline in serum irisin level. Associations between change in irisin level and changes in metabolic parameters were assessed using Pearson or Spearman correlation analysis and multivariable linear regression analysis. Results After the16-week exenatide treatment, serum irisin level significantly declined from baseline (3.22 ± 0.53 ng/mL vs. 3.35 ± 0.64 ng/mL, P = 0.031). Change in irisin level was positively associated with change in high-density lipoprotein cholesterol (HDL C) level ( r = 0.154, P = 0.035), and negatively associated with changes in triglyceride (TG) level ( r = −0.159, P = 0.029) and TG/HDL-C ratio ( r = −0.172, P = 0.018). These associations for TG level and TG/HDL-C ratio remained significant after multivariable adjustment. No significant association was observed between change in irisin level and glycemic control parameters. Conclusions Serum irisin level declines during the exenatide treatment in patients with T2DM, and this reduction is associated with change in lipid metabolism but not glycemic control, suggesting a potential link between dynamic change of irisin and lipid metabolism during the exenatide treatment.