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Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues

[ Vol. 16 , Issue. 2 ]

Author(s):

Anoop Mohamed Iqbal, Nasvin Imamudeen, Amjad Basheer, Sukrita Menon, Gisha Mohan, Tesil Nedumkallel Sani and Nisha Nigil Haroon*   Pages 197 - 206 ( 10 )

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 a robust reduction in HbA1c up to 1.5 - 1.8%. However, individual differences 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 a 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.

Keywords:

Diabetes mellitus, cardiovascular disease, cardiovascular outcome trials (CVOTs), glucagon-Like peptide 1, weight- loss.

Affiliation:

Division of Pediatric Endocrinology, Marshfield Medical Center, Wisconsin, Department of Medicine, Marshfield Medical Center, Wisconsin, Department of Medicine, University of Connecticut, CT, Amala Institute of Medical Sciences, Kerala, Universal College of Medical Science, Jubilee Mission Medical College and Research Institute, Kerala, Department of Medicine, Northern Ontario School of Medicine, Sudbury, ON



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