Title:Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues
Volume: 16
Issue: 2
Author(s): Anoop Mohamed Iqbal, Nasvin Imamudeen, Amjad Basheer, Sukrita Menon, Gisha Mohan, Tesil Nedumkallel Sani and Nisha Nigil Haroon*
Affiliation:
- Department of Medicine, Northern Ontario School of Medicine, Sudbury, ON,Canada
Keywords:
Diabetes mellitus, cardiovascular disease, cardiovascular outcome trials (CVOTs), glucagon-Like peptide 1,
weight- loss, semaglutide.
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.
