title: Beyond glucose lowering: glucagon-like peptide-1 receptor agonists, body weight and the cardiovascular system.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family: in the presence of elevated blood glucose, it stimulates insulin secretion and inhibits glucagon production. In addition, GLP-1 slows gastric emptying. GLP-1 secretion has also been reported to potentially affect patients with type 2 diabetes (T2DM) compared with non-diabetics and, as enzymatic inactivation by dipeptidyl peptidase-4 (DPP-4) shortens the GLP-1 half-life to a few minutes, GLP-1 receptor agonists such as exenatide twice daily (BID) and liraglutide have been developed, and have become part of the management of patients with T2DM. This review focuses on the potential beneficial effects of these compounds beyond those associated with improvements in blood glucose control and weight loss, including changes in the cardiovascular and central nervous systems.
  
  
  METHODS
  This was a state-of-the-art review of the literature to evaluate the relationships between GLP-1, GLP-1 receptor agonists, weight and the cardiovascular system.
  
  
  RESULTS
  GLP-1 receptor agonists improve glucose control and do not significantly increase the risk of hypoglycaemia. Also, this new class of antidiabetic drugs was shown to favour weight loss. Mechanisms may involve central action, direct action by reduction of food intake and probably indirect action through slowing of gastric emptying. The relative importance of each activity remains unclear. Weight loss may improve cardiovascular outcomes in patients with T2DM, although GLP-1 receptor agonists may have other direct and indirect effects on the cardiovascular system. Reductions in myocardial infarct size and improvements in cardiac function have been seen in animal models. Beneficial changes in cardiac function were also demonstrated in patients with myocardial infarcts or heart failure. Indirect effects could involve a reduction in blood pressure and potential effects on oxidation. However, the mechanisms involved in the pleiotropic effects of GLP-1 receptor agonists have yet to be completely elucidated and require further study.
  
  
  CONCLUSIONS
  These compounds may play an important role in the treatment of patients with T2DM as their potential effects go beyond glucose-lowering (weight loss, potential improvement of cardiovascular risk factors). However, to better understand their place in the management of T2DM, further experimental and clinical prospective studies are required.
authors.affiliation: Department of Endocrinology and Diabetes, Bocage Hospital and Inserm CRI 866, CHU of Dijon, Dijon, France.
authors.forename: B
authors.initials: B
authors.lastname: Vergès
authors.forename: C
authors.initials: C
authors.lastname: Bonnard
authors.forename: E
authors.initials: E
authors.lastname: Renard
mesh_terms: D001835:Body Weight; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000819:agonists*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide; D010455:Peptides / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D018819:Dipeptidyl Peptidase 4