Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues

Abstract

Abstract:: Glucagon like peptide- 1 receptor analogs (GLP-1RAs) are incretin mimetics with potent glucose-dependent insulinotropic action that translates to glycemic control in people with type-2 diabetes mellitus (T2DM). These agents potentially have the ability to stimulate proliferation or prevent apoptosis of pancreatic β-cells, induce weight-loss and provide vascular benefits in patients with T2DM. Newer GLP-1RA, semaglutide has shown robust reduction in HbA1c up to 1.5 - 1.8%. However individual differences do exist between the different GLP-1RAs, in terms of efficacy, pharmacokinetics, tolerability, and vascular protection. The potential of vascular protection offered by newer anti-diabetic agents has generated a lot of excitement in the field of diabetes, and to a large extent is now driving treatment decisions. So far, six cardiovascular outcome trials of GLP-1 RAs have been published, analyzing lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), long-acting exenatide (EXSCEL), dulaglutide (REWIND), and oral semaglutide (PIONEER 6) with a follow-up duration of 2-4 years. LEADER, REWIND and SUSTAIN-6 trials have demonstrated reduction in rates of major adverse cardiovascular events with active GLP-1 RA treatment but ELIXA, PIONEER 6 and EXSCEL have been neutral. In this review, we discuss the available evidence from randomized controlled trials (RCTs) analyzing the cardiovascular effects of various GLP-1 RAs with the aim of comparing individual drugs. We have also summarized the general aspects of GLP-1RAs that can be applied in clinical practice.

Utilization of glucagon-like peptide-1 receptor agonists in children and adolescents in China: a real-world study

“…Compared with people of the same age and gender, children and adolescents with higher BMI levels may have multiple cardiovascular risk factors ( 23 ). It has been demonstrated that different types of GLP-1RAs have individual differences in efficacy and vascular protection ( 24 ). For instance, liraglutide has been proven to lower the risk of major adverse cardiovascular events (MACE), while lixisenatide and slow-release exenatide had a neutral effect ( 25 ).…”

Efficacy and Cardiovascular Safety of Antidiabetic Medications

“…After the approval of exenatide for the management of T2DM in 2005, several molecules of GLP-1RAs were introduced into the global drug market, and newer agents are currently under development. Iqbal et al in this issue of the Journal, have provided us a concise and critical review titled “Efficacy and cardiovascular safety of GLP-1 receptor analogues” that analyses the biopharmaceutical properties, efficacy, and cardiovascular safety issues surrounding the use of GLP-1RAs [ 46 ]. Based on the evidence from multiple large RCTs and meta-analyses, the authors have concluded that the use of GLP-1RAs is associated with HbA1c reduction of up to 1.8%, depending on the baseline HbA1c and baseline body weight/ diabesity.…”

“…Iqbal et al have also elaborated the cardiovascular benefits associated with GLP-1RAs based on the extensive review of the 6 CVOTs using various molecules belonging to this drug class, such as lixisenatide liraglutide, exenatide, dulaglutide, and semaglutide [ 46 , 47 ]. CVOTs showed mortality reduction with only liraglutide and possibly semaglutide, the other three agents in the class did not show this benefit.…”