Hyperglycemia is associated with an increased risk of
cardiovascular disease, and the consequences of intensive
therapy may depend on the mechanism of the anti-diabetic agent(s) used to achieve a tight control. In animal models, stable analogues of
glucagon-like peptide-1 (GLP-1) were able to reduce
body weight and blood pressure and also had favorable effects on
ischemia following coronary reperfusion. In a similar way,
dipeptidyl peptidase IV (DPP-IV) showed to have favorable effects in animal models of
ischemia/reperfusion. This could be due to the fact that
DPP-IV inhibitors were able to prevent the breakdown of
GLP-1 and
glucose-dependent insulinotropic
polypeptide, but they also decreased the degradation of several vasoactive
peptides. Preclinical data for
GLP-1, its derivatives and inhibitors of the DPP-IV
enzyme degradation suggests that these agents may be able to, besides controlling glycaemia, induce cardio-protective and
vasodilator effects. Notwithstanding the many favorable cardiovascular effects of
GLP-1/
incretins reported in different studies, many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of
GLP-1 on cardiovascular endpoints. For this reason, long-term trials searching for positive cardiovascular effects are now in process, such as the CAROLINA and CARMELINA trials, which are supported by small pilot studies performed in humans (and many more animal studies) with
incretin-based
therapies. On the other hand, selective renal
sodium-
glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in
type 2 diabetes. However, it is quite early to draw conclusions, since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing. In this review, we will analyze the mechanisms underlying the cardiovascular effects of
incretins and, at the same time, we will present a critical position about the real value of these compounds in the cardiovascular system and its protection.