Combining Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors to Target Multiple Organ Defects in Type 2 Diabetes

Long-term risks of macro- and microvascular complications may be reduced in people with type 2 diabetes who achieve early and sustained glycemic control. Delays in attaining A1C goals are associated with poor long-term cardiovascular (CV) outcomes. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are glucose-lowering therapies that act through complementary mechanisms of action with regard to the pathophysiologic defects of type 2 diabetes. Trials of agents in both drug classes have demonstrated improvements in CV and renal outcomes. This review discusses the rationale for combination therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor, including early initiation of this combination in newly diagnosed patients. This combination may lead to timely glycemic control and potentially additive CV and renal benefits. Clinical studies of the combination have shown partially additive effects on A1C reduction, additive effects on weight reduction, and potentially synergistic effects on blood pressure reduction. Long-term studies are needed to determine whether the combination provides an additional effect on CV and renal outcomes compared with agents from either drug class when used alone.