Dipeptidyl Peptidase-4 Inhibitors and Their Effects on the Cardiovascular System

Abstract

It is well known that patients with type 2 diabetes mellitus (T2DM) are at increased risk of cardiovascular (CV) disease. Elevated plasma glucose levels that independently lead to increased cardiovascular risk, combined with associated co-morbidities such as obesity, hypertension, and dyslipidemia, further contribute to the development of CV complications. Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are a relatively new class of drugs used for the treatment of diabetes and recently have been widely used in clinical practice. They exert their actions through degradation inhibition of endogenous glucagon-like peptides (GLP-1) and glucose-dependent insulinotropic peptides (GIP), with a resulting increase in glucose mediated insulin secretion and a suppression of glucagon secretion. Since GLP-1 is known to have an impact not only on plasma glucose levels but also to have cardiovascular protective effects there is increased speculation of whether DPP-4 inhibitors will have similar effects. Though many short-term studies have been encouraging, ongoing long-term clinical trials on humans are needed to provide further clarity to the complete safety profiles of these agents in terms of cardiovascular risk, and whether they may exert potential cardiovascular benefit. This review includes available data on the cardiovascular effects of DPP-4 inhibitors as well as their overall safety profile.