Here, we summarized and critically interpret the available literature on (i) the mechanisms of action and the beneficial and potential adverse effects of SGLT2 inhibitors and GLP-1-R agonists; (ii) effects of SGLT2 inhibitors and GLP-1-R agonists on renal outcomes in T2DM patients; and (iii) cardiovascular benefits emerging from implying SGLT2 inhibitors and GLP-1-R agonists. The gene discussed is SLC5A2; the disease is type 2 diabetes mellitus.