title: Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control.
abstract: Type 2 diabetes mellitus is a well-established risk factor for cardiovascular disease (CVD). New therapeutic approaches have been developed recently based on the incretin phenomenon, such as the degradation-resistant incretin mimetic exenatide and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, as well as the dipeptidyl dipeptidase (DPP)-4 inhibitors, such as sitagliptin, vildagliptin, saxagliptin, which increase the circulating bioactive GLP-1. GLP-1 exerts its glucose-regulatory action via stimulation of insulin secretion and glucagon suppression by a glucose-dependent way, as well as by weight loss via inhibition of gastric emptying and reduction of appetite and food intake. These actions are mediated through GLP-1 receptors (GLP-1Rs), although GLP-1R-independent pathways have been reported. Except for the pancreatic islets, GLP-1Rs are also present in several other tissues including central and peripheral nervous systems, gastrointestinal tract, heart and vasculature, suggesting a pleiotropic activity of GLP-1. Indeed, accumulating data from both animal and human studies suggest a beneficial effect of GLP-1 and its metabolites on myocardium, endothelium and vasculature, as well as potential anti-inflammatory and antiatherogenic actions. Growing lines of evidence have also confirmed these actions for exenatide and to a lesser extent for liraglutide and DPP-4 inhibitors compared with placebo or standard diabetes therapies. This suggests a potential cardioprotective effect beyond glucose control and weight loss. Whether these agents actually decrease CVD outcomes remains to be confirmed by large randomized placebo-controlled trials. This review discusses the role of GLP-1 on the cardiovascular system and addresses the impact of GLP-1-based therapies on CVD outcomes.
authors.affiliation: Endocrinology Clinic, Hippokration Hospital, 49 Konstantinoupoleos Str., Thessaloniki, Greece. anagnwstis.pan@yahoo.gr
authors.forename: P
authors.initials: P
authors.lastname: Anagnostis
authors.forename: V G
authors.initials: VG
authors.lastname: Athyros
authors.forename: F
authors.initials: F
authors.lastname: Adamidou
authors.forename: A
authors.initials: A
authors.lastname: Panagiotou
authors.forename: M
authors.initials: M
authors.lastname: Kita
authors.forename: A
authors.initials: A
authors.lastname: Karagiannis
authors.forename: D P
authors.initials: DP
authors.lastname: Mikhailidis
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; 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* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D018027:Receptors, Glucagon / Q000502:physiology
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1