Obesity, cardiovascular and cerebrovascular disease: the role of GLP-1 receptor agonists

: Obesity prevalence is increasing dramatically worldwide, representing an important economic burden for our society. The treatment of obesity is quite challenging, potentially due to the fact that different phenotypes of the disease exist. Considering "obesities" rather than "obesity" and therefore considering different metabolism pathophysiology might help to better identify more tailored treatments. Glucagon-like peptide-1 receptor agonists (GLP-1RA), such as dulaglutide and semaglutide, are routinely prescribed for the treatment of type 2 diabetes mellitus (T2DM) in obese patients or those at high cardiovascular (CV) risk. Indeed, despite being developed for T2DM, GLP-1RA are increasingly recognized as anti-obesity treatments due to their weight loss effects. Furthermore, recent evidence showed that the CV prevention exerted by these molecules goes beyond that due to the weight loss and pleiotropic effects are reported. For instance, these drugs hold anti-inflammatory properties on vessels, enhance atherosclerotic plaque stability, reduce local advanced glycated end products receptor expression, lower monocyte-macrophages adhesion, and antagonize the effect of angiotensin-II. On the heart, GLP-1RA ameliorate cardiomyocyte survival and myocardial contractility, reduce cardiac hypertrophy, and are one of the few drugs that can reduce epicardial fat thickness. In this review, we summarize recent evidence concerning obesity/dysmetabolism and cardio-/cerebrovascular health. We further highlight the possible role of GLP-1RA as a treatment for obesity-related cardiovascular diseases by describing the principal molecular mechanisms known from current literature.