In the present study, we demonstrate that treatment with the GLP-1RA exenatide in adolescents with obesity improves glucose homeostasis, lowers circulating DPP-4 and proinsulin, and slightly increases glicentin, without affecting plasma levels of endogenous total GLP-1, glucagon, insulin or C-peptide. Here, DPP4 is linked to obesity due to melanocortin 4 receptor deficiency.