Impact of EMPA-REG OUTCOME(®) on the management of type 2 diabetes mellitus: a review for primary care physicians

Cardiovascular (CV) disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Most published trials of glucose-lowering agents have shown no significant CV benefit or increased risk of death or heart failure, with the exception of metformin. Three novel classes of glucose-lowering agents, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors, have been approved by the U.S. Food and Drug Administration for the treatment of T2DM in the United States and have also been available in other parts of the world in the past decade. Of the SGLT2 inhibitors, empagliflozin has demonstrated a CV benefit in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME®) while trials with other SGLT2 inhibitors are still ongoing. Empagliflozin has also provided possible renal protective benefit in those with mild-to-moderate renal impairment. The mechanisms behind the benefits seen with empagliflozin are likely multifactorial. Empagliflozin is the reasonable choice for add-on therapy in patients with long-standing T2DM who are at high CV risk as demonstrated in the EMPA-REG OUTCOME® study.