Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1 analogues and DPP-4-inhibitors.
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.
Rizzo
Manfredi
M
University of Palermo, Department of Clinical Medicine and Emerging Diseases, Via del Vespro, 141, 90127, Palermo, Italy. mrizzo@unipa.it
Rizvi
Ali A
AA
Spinas
Giatgen A
GA
Rini
Giovam Battista
GB
Berneis
Kaspar
K
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D012307:Risk Factors
D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D005947:Glucose