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The extra‐pancreatic effects of GLP‐1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems
Author(s) -
Seufert J.,
Gallwitz B.
Publication year - 2014
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/dom.12251
Subject(s) - type 2 diabetes , medicine , gastric emptying , lixisenatide , liraglutide , diabetes mellitus , exenatide , weight loss , disease , bioinformatics , endocrinology , obesity , biology , stomach
The glucagon‐like peptide‐1 receptor agonists ( GLP‐1RAs ) exenatide, liraglutide and lixisenatide have been shown to improve glycaemic control and beta‐cell function with a low risk of hypoglycaemia in people with type 2 diabetes. GLP ‐1 receptors are also expressed in extra‐pancreatic tissues and trial data suggest that GLP‐1RAs also have effects beyond their glycaemic actions. Preclinical studies using native GLP ‐1 or GLP‐1RAs provide substantial evidence for cardioprotective effects, while clinical trial data have shown beneficial actions on hypertension and dyslipidaemia in people with type 2 diabetes. Significant weight loss has been reported with GLP‐1RAs in both people with type 2 diabetes and obese people without diabetes. GLP‐1RAs also slow down gastric emptying, but preclinical data suggest that the main mechanism behind GLP‐1RA ‐induced weight loss is more likely to involve their effects on appetite signalling in the brain. GLP‐1RAs have also been shown to exert a neuroprotective role in rodent models of stroke, Alzheimer's disease and Parkinson's disease. These extra‐pancreatic effects of GLP‐1RAs could provide multi‐factorial benefits to people with type 2 diabetes. Potential adverse effects of GLP‐1RA treatment are usually manageable but may include gastrointestinal effects, increased heart rate and renal injury. While extensive further research is still required, early data suggest that GLP‐1RAs may also have the potential to favourably impact cardiovascular disease, obesity or neurological disorders in people without diabetes in the future.