<h4>Purpose of review</h4>This review will summarize the most contemporary trials for glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and present guidance on management and recommendations on adjunctive tapering of insulin in patients with insulin-dependent diabetes mellitus, which we term "de-insulinization."<h4>Recent findings</h4>GLP1-RA and SGLT2-i are the principal classes of diabetes medications evidencing cardiovascular benefit. The gene discussed is GLP1R; the disease is diabetes mellitus.