The impact of GLP-1 analogues on cardiovascular risk

Abstract The population of patients with type 2 diabetes is characterized by higher cardiovascular risk than the general population. It has been shown that glycemic control declines the incidence of serious cardiovascular events. The aim of this literature review is to elucidate the effect of GLP-1 analogues on cardiovascular risk factors. Interestingly, recent scientific reports suggest that GLP-1 analogues reduce cardiovascular risk also in a mechanism unrelated to the hypoglycemic effect of the drug, but also apart from weight loss. The direct cardioprotective effect of GLP-1 analogues is associated with the expression of GLP-1 receptors in heart and vascular smooth muscle cells. Moreover, a protective effect of GLP-1 analogues has been found in cell interactions between endothelium, immune system cells, thrombocytes in preventing the formation of atherosclerotic plaques. GLP-1 receptors are also expressed in epicardial fat. Epicardial fat modulation after treatment with GLP-1 analogues may decline the risk of serious adverse cardiovascular events. Clinical cardiovascular outcome trials (CVOT) were conducted to elucidate the influence of GLP-1 analogues on the cardiovascular system in patients with type 2 diabetes. Five CVOT studies of GLP-1 analogues have shown that therapy with these drugs reduces cardiovascular risk in type 2 diabetes patients. However, two studies (ELIXA and EXSCEL) demonstrated a neutral effect of lixisenatide and exenatide on cardiovascular risk in type 2 diabetes patients. Moreover, it was also shown that semaglutide declines cardiovascular risk also in obese individuals without diabetes. Therefore, international guidelines recommend the implementing liraglutide, semaglutide and dulaglutide in the therapy regime to reduce the risk of cardiovascular events in patients at higher cardiovascular risk.