title: The extra-pancreatic effects of GLP-1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems.
abstract: 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.
authors.affiliation: Division of Endocrinology and Diabetology, Department of Medicine II, Albert-Ludwigs University Medical Center, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Seufert
authors.forename: B
authors.initials: B
authors.lastname: Gallwitz
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D058065:Diabetic Cardiomyopathies / Q000517:prevention & control; D003929:Diabetic Neuropathies / Q000517:prevention & control; D019317:Evidence-Based Medicine; D000077270:Exenatide; D005767:Gastrointestinal Diseases / Q000517:prevention & control; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D000069450:Liraglutide; D009765:Obesity / Q000150:complications / Q000517:prevention & control; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D000069450:Liraglutide; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: GLP-1; cardiovascular; central nervous system; exenatide; gastrointestinal; liraglutide; lixisenatide; receptor agonists