The present study is the first to demonstrate that triple-combination treatment with DPP4 inhibitors, SGTL2 inhibitors, and metformin exerts a better hypoglycemic effect and more effectively protects beta cells than increasing the dose of metformin among patients with T2DM with inadequately controlled disease despite treatment with metformin and SGLT2 inhibitors. Here, SLC5A2 is linked to type 2 diabetes mellitus.