Despite the availability of a number of therapeutic options, management of type 2 diabetes (T2DM) and hyperglycemia remains suboptimal. Evidence shows that physicians are not adequately individualizing incretin-based therapies as there is lack of clear understanding of the similarities and differences between various incretin-based therapies. Additionally, sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors, a very recent addition to the therapeutic armamentarium, are not adequately utilized in managing patients with T2DM due to a lack of awareness or an increased concern regarding their safety, efficacy, and the mechanism of action. Insulin therapy is also not initiated or intensified appropriately due to a lack of clear understanding on when to add and how to intensify them and, more importantly, due to fear of increasing the risk of hypoglycemia in patients. To address these gaps, in the first section of this educational activity, the expert faculty will review the current understanding of the risks associated with hypoglycemia—one of the main factors that limit the successful use of insulin therapy—and when to initiate insulin therapy, as well as the available data on the risk of hypoglycemia with emerging agents. The expert faculty will also provide practical strategies on how to minimize the risk of hypoglycemia in patients. In the second section, the expert faculty will highlight the differences between the various incretin-based therapies in addition to providing strategies for physicians to individualize their choice of incretin-based therapy. The expert faculty will also review the mechanism of action, safety, efficacy, and the appropriate place for this class of therapies in the treatment continuum. In the third section, the expert faculty will discuss the mechanism of action, safety, and efficacy of the currently available SGLT2 inhibitors as well as the appropriate use of these newer agents in T2DM management.This CME Multimedia Activity is also available through the Website of The American Journal of Medicine (www.amjmed.com). Click on the CME Multimedia Activity button in the navigation bar for full access. Or access: www.elseviercme.com/537.