Impact of incretin-related agents on endothelial cell function

Incretin-related drugs, such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, have been clinically available and widely used to treat patients with type 2 diabetes mellitus. Accumulating evidence indicates that these agents exert glycemic control and have various other favorable effects, including prevention of atherosclerosis. It is important to assess and manage early-phase atherosclerosis, but whether diabetic therapeutics including incretin-related drugs improve or maintain vascular endothelial cell function has not been fully determined. We previously published prospective clinical trials focused on flow-mediated dilation in patients with type 2 diabetes, who did not have severe atherosclerosis, using two different incretin-related drugs: a DPP-4 inhibitor and a GLP-1 analogue. These trials showed that these therapeutic agents did not improve endothelial cell function. In this article, we discuss how incretin-related drugs contribute, if at all, to vascular endothelial cell function, atherosclerosis, and beta-cell function, based on our clinical trials and previous evidence.