Abstract | The aim of this thesis is to illustrate the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of type 2 diabetes with regard to metabolic and pleiotropic effects such as cardio- and nephroprotection.
Several studies have shown that GLP-1 RAs such as liraglutide, semaglutide, or dulaglutide reduce body weight and should be used especially in T2DM when body weight reduction is a treatment goal. This is not only for cosmetic reasons, but could also help reduce obesity-related conditions such as dyslipidemia, inflammation, insulin resistance, or elevated blood pressure. Overall, the organ-protective effects demonstrated in several studies with GLP-1 RAs are promoted. The objective of this work is to provide an overview of the mode of action, metabolic, pleiotropic and organ protective effects of GLP-1 RAs in the treatment of T2DM. |
Abstract (english) | The aim of this review was to highlight the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of type 2 diabetes with regard to metabolic and pleiotropic effects such as cardio- and nephroprotection.
GLP-1 RAs exert their main action by stimulating glucose-dependent insulin release from beta cells and inhibiting glucagon secretion from alpha cells. They have also been shown to slow gastric emptying and reduce food intake. Ultimately, this leads to a reduction in HbA1c levels and body weight. These features make GLP-1 RAs a unique treatment option.
In addition, GLP-1 RAs act on the heart and show outstanding cardioprotective properties, including an increase in glucose utilization, left ventricular function and myocyte survival.
Cardiovascular outcome studies have confirmed that GLP-1 RAs reduce the risk of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The antiatherosclerotic effects of GLP-1 RAs are associated with the action of GLP-1 on blood vessels, leading to increases in vasodilation, blood flow, plaque stability, and endothelial function, as well as decreases in smooth muscle cell proliferation, blood pressure, and platelet aggregation. Furthermore, GLP-1 RAs have been shown to reduce the development of new-onset macroalbuminuria, urinary albumin excretion and to slow the decline in estimated glomerular filtration rate.
Nevertheless, GLP-1 RAs also have some disadvantages, mostly associated with gastrointestinal symptoms such as nausea and vomiting. An increase in heart rate has also been noted in several studies.
The future of incretin therapy is very promising, with triple agonists being developed that will provide even more effective glycemic control and body weight reduction in patients with type 2 diabetes. |