Dipeptidyl Peptidase IV Inhibitors and Ischemic Myocardial Injury

Diabetes mellitus is a major risk factor for cardiovascular events and patient death. Many animal and clinical studies are now being conducted exploring the potential of antidiabetic drugs such as glucagon-like peptide I (GLP-I) agonists and dipeptidyl peptidase IV (DPP-IV) inhibitors to improve cardiovascular outcomes. This review summarizes the effect of DPP-IV inhibitors on myocardial ischemia-reperfusion injury in animal models. The DPP-IV inhibitors prevent the rapid degradation and inactivation of incretins and lead to the accumulation of GLP-I and other chemokines and cytokines, which appear to have both GLP-I receptor-dependent and -independent cardioprotective, antiapoptotic, and anti-inflammatory effects. Conflicting results, however, have been reported regarding the effect of DPP-IV inhibitors on infarct size in nondiabetic and diabetic animal models. Some studies suggest that DPP-IV inhibitors given as part of preconditioning can decrease infarct size while others found no difference in infarct size compared to placebo. As postconditioning, one study suggested it does provide cardioprotection. No clinical trials have yet been conducted addressing the effect of DPP-IV inhibitors on infarct size. Thus far, clinical trials have not demonstrated improvement in cardiovascular events or mortality from any cause in high cardiovascular risk, type 2 diabetic patients with the use of DPP-IV inhibitors. Although further experiments and clinical trials will be warranted to confirm the results of these studies, the myocardial protection afforded by DPP-IV inhibitors in preclinical animal studies poses a potential breakthrough role for antidiabetic medications in attenuation of ischemia-reperfusion injury that occurs with cardiovascular disease.