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Glucagon‐like peptide‐1‐based therapies and cardiovascular disease: looking beyond glycaemic control
Author(s) -
Anagnostis P.,
Athyros V. G.,
Adamidou F.,
Panagiotou A.,
Kita M.,
Karagiannis A.,
Mikhailidis D. P.
Publication year - 2011
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2010.01345.x
Subject(s) - exenatide , vildagliptin , saxagliptin , liraglutide , medicine , sitagliptin , incretin , endocrinology , type 2 diabetes , glucagon like peptide 1 , diabetes mellitus , metformin , gastric emptying , pharmacology , stomach
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.