This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment.