New developments in incretin-based therapies: the current state of the field

To update readers on developments in incretin therapies since the previous JAANP supplement in 2007; specifically, to describe clinical data for currently available incretin-based therapies as well as those under consideration by regulatory agencies.

Medline search for peer-reviewed publications.

Incretin-based therapies have pharmacologic properties that avoid some key limitations of previous treatments, such as hypoglycemia and weight gain. Certain agents also lower blood pressure and have the potential to reduce cardiovascular risk. The insulin-secreting action of incretin-based therapies only occurs under hyperglycemic conditions, thus minimizing the risk of hypoglycemia, unless combined with a sulfonylurea. The DPP-4 inhibitors are orally administered and demonstrate modest A1c reductions (0.6%-0.8%); the best results occur when combined with metformin. Glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and exenatide have shown greater A1c reductions (typically ≥ 1.1% and as high as 1.7%), and these agents have beneficial ancillary effects, including weight and systolic blood pressure reduction. Both DPP-4 inhibitors and GLP-1 receptor agonists have shown the ability to improve pancreatic beta-cell function in early studies.

Data are provided on the efficacy and tolerability of approved incretin therapies, and on treatments currently in regulatory review, in order to inform readers and guide their practice.