GLP-1 receptor agonists and reduction of cardiometabolic risk: Potential underlying mechanisms

Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):2814-2821. doi: 10.1016/j.bbadis.2018.05.012. Epub 2018 May 18.

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic condition with an elevated impact on cardiovascular (CV) risk. The innovative therapeutic approaches for T2DM - incretin-based therapies (IBTs), including glucagon-like peptide 1 (GLP-1) receptor agonists, have become popular and more widely used in recent years. The available scientific data from clinical studies and clinical practice highlights their beyond glucose-lowering effects, which is achieved without any increase in hypoglycaemia. The former effects include reduction in body weight, lipids, blood pressure, inflammatory markers, oxidative stress, endothelial dysfunction, and subclinical atherosclerosis, thus reducing and potentially preventing CV events. In fact, the introduction of IBTs is one of the key moments in the history of diabetes research and treatment. Such therapeutic strategies allow customization of antidiabetic treatment to each patient's need and therefore obtain better metabolic control with reduced CV risk. The aim of the present paper is to provide a comprehensive overview of the effects of GLP-1RA on various cardiometabolic markers and overall CV risk, with particular attention on recent CV outcome studies and potential mechanisms. In particular, the effects of liraglutide on formation and progression of atherosclerotic plaque and mechanisms explaining its cardioprotective effects are highlighted.

Keywords: Cardiometabolic parameters; Cardiovascular risk; Glucagon-like peptide 1 receptor agonists; Type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptides / pharmacology
  • Glucagon-Like Peptides / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Incretins / pharmacology*
  • Incretins / therapeutic use
  • Liraglutide / pharmacology
  • Liraglutide / therapeutic use
  • Plaque, Atherosclerotic / blood
  • Plaque, Atherosclerotic / drug therapy*
  • Plaque, Atherosclerotic / etiology
  • Plaque, Atherosclerotic / metabolism

Substances

  • Blood Glucose
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Incretins
  • semaglutide
  • Glucagon-Like Peptides
  • Liraglutide