DPP4 inhibitors and GLP-1 receptor agonists used in incretin-based strategies treat Type 2 diabetes with different modes of action. The pharmacological blood GLP-1R agonist concentration targets pancreatic and some extrapancreatic GLP-1R, whereas DPP4i favors the physiological activation of the gut-brain-periphery axis that could allow clinicians to adapt the management of Type 2 diabetes, according to the patient's pathophysiological characteristics.