Based on the observation of a large, unselected population of patients with type 2 diabetes starting second-line therapy after metformin monotherapy failure, this study investigated whether newer diabetes agents such as DPP-4i, SGLT2i, and GLP-1-RA could delay or prevent clinically relevant outcomes and improve cost-effectiveness profiles compared with conventional SU. The gene discussed is GLP1R; the disease is type 2 diabetes mellitus.