Objective. To review the current literature investigating the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk factors of cardiovascular disease (CVD). Methods. We conducted a search of PubMed and MEDLINE database, using the term DPP-4 inhibitor in combination with the following terms: metabolic syndrome, hypertension, dyslipidemia, insulin resistance, obesity, and CVD. We reviewed 100 relevant studies out of 227 articles, excluding single case reports, studies using animal models, and reports not written in English. We included 38 references in this review article. Results. The majority of the recent clinical studies have demonstrated that DPP-4 inhibitors have beneficial effects on cardiovascular (CV) system. These agents may have the potential to lower blood pressure, improve lipid profile and endothelial dysfunction, decrease the macrophage-mediated inflammatory response, and prevent myocardial injury. Conclusion. DPP-4 inhibitors have some CV protective effects in type 2 diabetes mellitus (T2DM) in addition to their antidiabetic actions. Long-term outcome clinical trials are under way to investigate the effects of the DPP-4 inhibitors on the elevated CV risks in patients with T2DM. Further investigation in a large cohort is warranted to assess the exact mechanisms of CV protective effects of DPP-4 inhibitors. 1. Introduction T2DM is a well-studied chronic metabolic disease that when left untreated or insufficiently managed can cause serious microvascular and macrovascular complications. The blood glucose-lowering agents such as metformin, sulfonylurea derivatives, and insulin all can improve glycemic control in patients with T2DM, but these agents have limited or no effect on the associated CV risk factors accompanying T2DM including dyslipidemia, hypertension, and obesity. Treatment with both sulfonylurea derivatives and insulin has been associated with weight gain, which may diminish any positive effects on vascular endpoints, and thiazolidinediones have even been associated with an increased risk of CVD [1, 2]. Thus, there is a need to ensure that any new medication for T2DM is not associated with a deleterious effect on CV outcomes. Glucose homeostasis is achieved by a complex interaction of hormones, principally insulin, glucagon, amylin, and incretins. Incretins are secreted from gastrointestinal tract in response to food intake and have several systemic effects, including glucose-dependent stimulation of insulin secretion by pancreatic beta-cells [3]. Two incretins have been identified: glucagon-like peptide-1 (GLP-1),
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