Incretin-Based Therapies for the Treatment of Type 2 Diabetes – DPP-4 Inhibitors and Incretin Mimetics

Current Therapies in Type 2 Diabetes
The prevalence of type 2 diabetes is rising dramatically consecutively leading to an
increase of complications of the disease. It is predicted that the total number of people with diabetes may be 370 million worldwide by the year 2030, along with a substantial rise in prediabetic conditions [1]. Since type 2 diabetes is increasing and
most patients do not reach their therapeutic goals, novel treatment options are
needed.

While insulin resistance is constant in the course of type 2 diabetes, islet function
continuously declines over time. Disease progression of type 2 diabetes is characterized by the loss of islet function. Hyperglycemia, free fatty acids, cytokines, adipokines and toxic metabolic products may lead to a loss of
-cell function and
-cell mass in the islets. The  cells in the islet additionally develop a disturbance of glucagon secretion. In healthy subjects, glucagon secretion is suppressed under hyperglycemic conditions,
whereas in type 2 diabetes glucagon secretion is elevated, leading to excessive
glucose production by the liver [2].
The therapeutic options currently available do not address the problem of islet-cell
dysfunction. Sulfonylureas and glinides both exclusively stimulate insulin secretion
from the
cells; metformin and glitazones act on insulin resistance, and -glucosidase delays the breakdown of complex carbohydrates. Exogenous insulin replaces the endogenous secretory insulin deficit, although it potentially causes weight gain and hypoglycemia. The progressive loss of islet function observed in type 2 diabetes is not ameliorated by any of the current therapeutic options [3].