Role of glucagon-like peptide-1 receptor agonists in the treatment of obesity, cardiovascular disease, and cerebrovascular disease.

Worldwide prevalence of obesity is increasing dramatically, imposing a significant economic burden on our society. Treatment of obesity is challenging, potentially due to different disease phenotypes. Taking into consideration "obesities" rather than "obesity," and thus aiming to understand different pathophysiologic mechanisms of individual phenotypes, might help identify more tailored treatment strategies. Glucagon‑like peptide‑1 receptor agonists (GLP‑1RAs), for example, dulaglutide and semaglutide, are routinely prescribed for the treatment of type 2 diabetes mellitus (T2DM) in patients with obesity or those at a high cardiovascular (CV) risk. Indeed, despite having been developed for T2DM, GLP‑1RAs are being increasingly often recognized as antiobesity medications due to their weight loss effects. Furthermore, recent evidence has shown that the extent of CV prevention offered by these drugs goes beyond that associated with their weight loss and pleiotropic effects. For instance, they exert anti‑inflammatory effects on vessels, enhance atherosclerotic plaque stability, reduce local advanced glycation end product receptor expression, lower monocyte‑macrophage adhesion, and antagonize the effect of angiotensin II. In the heart, GLP‑1RAs ameliorate cardiomyocyte survival and myocardial contractility, reduce cardiac hypertrophy, and are one of few drugs that can reduce epicardial fat thickness. In this review, we summarize recent evidence concerning the effects of GLP‑1RAs on obesity / dysmetabolism and on cardio- / cerebrovascular health. We further highlight the possible role of GLP‑1RAs in the treatment of obesity‑related CV diseases by describing the principal molecular mechanisms reported in the current literature.