title: Extraglycemic effects of glp-1-based therapeutics: addressing metabolic and cardiovascular risks associated with type 2 diabetes.
abstract: BACKGROUND
  To examine whether widespread tissue expression of the glucagon-like peptide (GLP)-1 receptor supports the possibility of differential effects of GLP-1-based therapeutics on cardiac function, blood pressure, food intake, gastric emptying, and other regulatory activities. GLP-1 receptor agonists (RAs) have demonstrated pleiotropic effects on overweight/obesity, hypertension, dyslipidemia, and cardiovascular (CV) disease. Food-regulatory effects have been demonstrated in preclinical and clinical trials, including reduced gastric motility and food intake leading to body weight reductions. Native GLP-1 and GLP-1 RAs have demonstrated cardioprotective effects in preclinical models.
  
  
  METHODS
  Using PubMed, we performed a search of the recent literature on GLP-1 and GLP-1 RAs.
  
  
  RESULTS
  Preliminary clinical data indicate native GLP-1 has beneficial effects on endothelial cell function and vascular inflammation. Native GLP-1 and GLP-1 RAs have demonstrated renoprotective and antihypertensive effects, and reductions in lipid parameters. The GLP-1 RA liraglutide has also demonstrated positive effects on such markers of endothelial dysfunction as tumor necrosis factor-α and plasminogen activator inhibitor-1.
  
  
  CONCLUSIONS
  Preliminary data suggest GLP-1 RAs could benefit type 2 diabetes patients at risk for CV comorbidities. Additional studies are needed to confirm the extraglycemic and extrapancreatic effects and determine whether outcomes will translate into beneficial effects for patient care.
authors: Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, United States.
authors: Susan
authors: S
authors: Herzlinger
authors: Edward S
authors: ES
authors: Horton
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D018027:Receptors, Glucagon / Q000378:metabolism; D012307:Risk Factors; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1