Incretin-based therapies: therapeutic rationale and pharmacological promise for type 2 diabetes.
OBJECTIVE
To highlight the therapeutic promise of the incretin hormone glucagon-like peptide-1 (GLP-1), the consequent rationale for therapies acting through GLP-1-mediated pathways in type 2 diabetes mellitus (T2DM), and the emerging clinical role of the dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 receptor agonists.


METHODS
The PubMed database was searched (using terms including incretins, GLP-1, GIP, DPP-4), along with recent ADA and EASD abstracts.


CONCLUSIONS
Many traditional drugs used for T2DM fail to achieve and maintain glycemic control, and possess limitations such as risk for hypoglycemia and weight gain. GLP-1 is a gut-derived hormone that glucose-dependently stimulates insulin secretion while simultaneously reducing gastric emptying and appetite. Other physiological actions of GLP-1 may benefit the cardiovascular system and beta-cell function. Recently developed drug therapies that mimic or prolong the action of this hormone, therefore, have great promise in the treatment of T2DM.


CONCLUSIONS
The GLP-1 receptor agonists and DPP-4 inhibitors are incretin-based therapies that are now becoming established as effective therapies for T2DM to be used either as monotherapy or added to other antidiabetes drugs. They enable improvements to be made in glycemic control without weight gain, with a low risk for hypoglycemia, and with potential additional clinical benefits.
Wick
Allison
A
Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA. awick@med.miami.edu
Newlin
Kelley
K
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000627:therapeutic use*
D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1