Endocrine Abstracts

The incretin hormone Glucagon-like peptide-1 (GLP-1) has various non-glycaemic properties. Among those, cardiovascular effects have been described in animal studies and in clinical studies in patients with type 2 diabetes that have been treated with GLP-1 receptor agonists (GLP-1RA). In animal studies, GLP-1 and GLP-1RA have lead to a decrease in ischaemic areas in artificial myocardial infarct models. Additionally, in some clinical studies, an improvement in left ventricular function was observed as well as a decrease for catecholamine requirement in post-surgical patients after coronary bypass graft surgery. The pathophysiological explanations for these effects are a possible improvement in substrate utilization of the myocardium as well as vascular effects mediated by the activation of cardiovascular GLP-1 receptors and a consecutive amelioration of hypertension. In recent years, randomized, prospective cardiovascular safety trials have been initiated or performed with GLP-1RA in patients with type 2 diabetes and concomitant cardiovascular disease or cardiovascular risk factors. Results from three of these studies have been published so far. In the ELIXA-trial, the short acting GLP-1RA lixisenatide was given as add on to a standard antidiabetic therapy in patients after an acute cardiovascular event. In comparison to an established diabetes therapy, lixisenatide demonstrated non-inferiority and cardiovascular safety. The LEADER-study performed with liraglutide in patients with type 2 diabetes and concomitant cardiovascular risk or disease showed a highly significant 13% relative risk reduction in the 3-point MACE (MACE = multiple adverse cardiovascular events; combined endpoint of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) after 54 months. This result was primarily driven by a significant reduction of cardiovascular death by 22%. Semaglutide, a long-acting GLP-1RA for once weekly injection that is not approved yet, lead to a significant 26% relative risk reduction in the 3-point MACE in its clinical phase III study programme. From these data, the hypothesis that the activation of the GLP-1 receptor has beneficial cardiovascular effects, is strongly supported and it has now been demonstrated in two studies, that patients with type 2 diabetes and cardiovascular disease may profit from a therapy with GLP-1RA regarding their cardiovascular outcomes.