Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1 analogues and DPP-4-inhibitors

Expert Opin Investig Drugs. 2009 Oct;18(10):1495-503. doi: 10.1517/14728220903241633.


Background: Type 2 diabetes is a chronic, progressive disease with a multi-faceted pathophysiology. Beyond the known defects of insulin resistance and beta-cell insufficiency, derangement of incretin hormones normally produced from the gut wall in response to food intake play an important role. In recent years, the 'incretin-based' therapies (IBTs) have been developed to address hyperglycemia through either mimicking the action of the endogenous incretin glucagon-like polypeptide (GLP-1) (GLP-1 receptor agonists) or by inhibiting the activity of the enzyme that degrades GLP-1 (the dipeptyl peptidase-4 inhibitors).

Objective: We reviewed available evidence on the glucose lowering and anti-atherogenic effects of IBT.

Results: In addition to their glucose-lowering and weight-neutral or weight-reducing actions, IBT decrease systolic blood pressure and improve fasting and postprandial lipid parameters by reducing total-cholesterol, low-density lipoprotein-cholesterol and triglycerides concentrations, and increasing high-density lipoprotein-cholesterol values. Reduced high-sensitivity C-reactive protein levels and improved endothelial dysfunction have been reported too.

Conclusions: IBT have several beneficial effects on cardiovascular risk factors and, for this reason, it has been recently suggested to extend the use of these drugs in diabetic patients with cardiovascular complications. Yet, the long-term effects of IBT on subclinical or clinical atherosclerosis remain to be established by future studies.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / prevention & control
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dipeptidyl Peptidase 4
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucose / metabolism
  • Humans
  • Incretins / metabolism*
  • Risk Factors


  • Dipeptidyl-Peptidase IV Inhibitors
  • Incretins
  • Glucagon-Like Peptide 1
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Glucose