title: Glucagon-like peptide-1 (GLP-1) receptor agonists: Differentiating the new medications.
abstract: BACKGROUND
  Glucagon-like peptide-1 (GLP-1) has been the focus of considerable research activity in the treatment of type 2 diabetes mellitus (T2DM) because the incretin effect is significantly reduced or absent in individuals with T2DM. Thus, pharmacologic efforts to develop medications that mimic the actions of GLP-1 have become a target for improving or reversing chronic hyperglycemia. Two GLP-1 receptor agonists are commercially available: exenatide twice daily (b.i.d.) and liraglutide once daily (q.d.). Targeted and individualized intensification of diabetes management can best be accomplished with a thorough understanding of these new medications.
  
  
  METHODS
  Information was gathered through a search of MEDLINE and PubMed for GLP-1 and glycemic management in patients with type 2 diabetes.
  
  
  RESULTS
  Activation of the GLP-1 receptors on the β-cells results in enhanced levels of insulin biosynthesis, β-cell proliferation, resistance to β-cell apoptosis, and enhanced β-cell survival in both humans and rodents; yet, the risk of hypoglycemia is minimized because insulin production and exocytosis occurs in a glucose-dependent manner. The efficacy and safety of the two commercially available GLP-1 receptor agonists, liraglutide and exenatide, in managing postprandial glycemia have been well documented in numerous clinical trials, in which reductions in glycosylated hemoglobin (HbA1c) levels of -0.79% to -1.12% have been demonstrated. Weight reduction/maintenance and improvements in blood pressure and lipidemia have also been reported.
  
  
  CONCLUSIONS
  Because GLP-1 receptor agonists work in a glucose-dependent manner, they are likely to reduce hyperglycemia safely, without a marked fluctuation toward hypoglycemia. In the process of acutely restoring β-cell function, GLP-1 agonists may allow patients to achieve HbA(1c) <7% without experiencing weight gain or hypoglycemia. The ability of GLP-1 receptor agonists to improve blood pressure and postprandial lipidemia in the context of weight neutrality or weight loss may have the potential to ameliorate some of the cardiovascular risks observed in patients with T2DM.
authors: Loma Linda University School of Medicine, Loma Linda, USA.
authors: Jeffrey R
authors: JR
authors: Unger
authors: Christopher G
authors: CG
authors: Parkin