The pathogenetic mechanisms causing
type 2 diabetes are complex, and include a significant reduction of the
incretin effect. In patients with
type 2 diabetes,
GLP-1 secretion may be impaired, while GIP secretion seems unaffected. In contrast, the insulinotropic activity of GIP is severely altered, whereas that of
GLP-1 is maintained to a great extent. Better understanding of the role of
incretin hormones in
glucose homeostasis has led to the development of
incretin-based
therapies that
complement and offer important advantages over previously used agents.
Incretin-based agents have significant
glucose-lowering effects, promote
weight loss (or are weight-neutral), inhibit
glucagon secretion while maintaining counter-regulatory mechanisms, exhibit cardiovascular benefits, and protect β-cells while possessing a low risk profile. At present,
incretin-based
therapies are most widely used as add on to
metformin to provide sufficient
glycemic control after
metformin failure. However, they are also recommended as monotherapy early in the disease course, and later in triple combination. These agents may also be a promising therapeutic tool in prediabetic subjects. Therefore, a therapeutic algorithm is needed for their optimal application at different stages of diabetes, as suggested in this article.