This article reviews many of the key incretin clinical trials, with a focus on the efficacy and safety of glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors compared with placebo and other glucose-lowering agents used as comparators. These agents have been tested either as monotherapy or in combination with one or more oral antidiabetic drugs (OADs). The article also discusses some of the important clinical differences between GLP-1 receptor agonists and DPP-4 inhibitors.