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.