We systematically evaluated the comparative effectiveness and safety associated with 4 categories of diabetes drugs: sulfonylurea, dipeptidyl peptidase-4 inhibitor (DPP4I), glucagon-like peptide-1 receptor agonist (GLP1RA), and sodium-glucose cotransporter-2 inhibitor (SGLT2I) when added onto existing metformin therapy using a clinical database covering 8 million patients across 5 University of California (UC) academic health centers that have been linked to form UC Health (eMethods in Supplement 1). The gene discussed is DPP4; the disease is diabetes mellitus.