This cohort study assesses the association of high out-of-pocket costs and initiation of a sodium-glucose cotransporter 2 (SGLT2) inhibitor or glucagon-like peptide-1 receptor agonist (GLP-1 RA) among adults who are treated with metformin and have type 2 diabetes and established cardiovascular disease. The gene discussed is SLC5A2; the disease is type 2 diabetes mellitus.