Cardiovascular protection by DPP-4 inhibitors in preclinical studies: an updated review of molecular mechanisms

Abstract

Dipeptidyl peptidase 4 (DPP4) inhibitors are a class of antidiabetic medications that cause glucose-dependent increase in incretins in diabetic patients. One of the two incretins, glucagon-like peptide-1 (GLP-1), beside its insulinotropic activity, has been studied for extra pancreatic effects. Most of DPP4 inhibitors (DPP4i) have been investigated in in vivo and in vitro models of diabetic and nondiabetic cardiovascular diseases including heart failure, hypertension, myocardial ischemia or infarction, atherosclerosis, and stroke. Results of preclinical studies proved prominent therapeutic potential of DPP4i in cardiovascular diseases, regardless the presence of diabetes. This review aims to present an updated summary of the cardiovascular protective and therapeutic effects of DPP4 inhibitors through the past 5 years focusing on the molecular mechanisms beneath these effects. Additionally, based on the results summary presented here, future studies may be conducted to elucidate or illustrate some of these findings which can add clinical benefits towards management of diabetic cardiovascular complications.

Beyond Blood Sugar: Investigating the Cardiovascular Effects of Antidiabetic Drugs

“…In a review by Zakaria et al, it was found that DPP-4 inhibitors had beneficial effects on the cardiovascular system by modulating the levels of vasoactive cardio-protectant peptides like B-type natriuretic peptide (BNP), stromal cell-derived factor 1α (SDF-1α) and substance P [ 53 ]. They also exert positive effects on the cardiovascular system through mechanisms like reducing hyperglycemia, reducing oxidative damage and inflammation, promoting tissue repair, and protecting the endothelial function, leading to better perfusion of the myocardium [ 53 ].…”

DPP‐4 inhibitor sitagliptin treatment results in altered myocardial metabolic proteome and oxidative phosphorylation in a swine model of chronic myocardial ischemia

“…Interestingly, there is a disconnect between animal studies of DPP‐4 inhibitors and the aforementioned clinical studies on the effects of DPP‐4 inhibitors in patients with CAD. Mouse studies have shown increased angiogenesis, decreased ischemic reperfusion injury, and decreased coronary atherosclerosis with DPP‐4 inhibitors (Abbas et al., 2018 ; Al‐Awar et al., 2018 ; Bradic et al., 2021 ; Fan et al., 2020 ; Khodeer et al., 2019 ; Zakaria et al., 2022 ). Other mouse studies modeling heart failure have shown increased cardiac function and decreased diastolic dysfunction with DPP‐4 inhibitors (Beraldo et al., 2019 ; Esposito et al., 2017 ).…”