Extraglycemic effects of glp-1-based therapeutics: addressing metabolic and cardiovascular risks associated with type 2 diabetes

Diabetes Res Clin Pract. 2013 Apr;100(1):1-10. doi: 10.1016/j.diabres.2012.11.009. Epub 2013 Jan 14.


Context: 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.

Evidence acquisition: Using PubMed, we performed a search of the recent literature on GLP-1 and GLP-1 RAs.

Evidence synthesis: 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.

Conclusion: 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.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetes Mellitus, Type 2 / prevention & control
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / physiopathology
  • Diabetic Angiopathies / prevention & control
  • Endothelium, Vascular / drug effects
  • Female
  • Gastric Emptying / drug effects
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Receptors, Glucagon / metabolism
  • Risk Factors
  • Treatment Outcome
  • Weight Loss / drug effects


  • Anti-Inflammatory Agents
  • Antihypertensive Agents
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1