Abstract

Incretin for the continuing treatment of secondary failure to metformin in Type 2 diabetes

Author(s): Baptist Gallwitz

For the treatment of Type 2 diabetes, incretin-based therapies have been an established treatment since their introduction in 2006. GLP‑1 receptor agonists as an injectable therapy and DPP‑4 inhibitors as oral antidiabetic agents have a strictly glucose-dependent action on insulin and glucagon secretion, resulting in a negligible intrinsic hypoglycemia risk. The GLP‑1 receptor agonists only act by stimulating the GLP‑1 receptor directly at receptor ligand concentrations in the pharmacological concentration range. They decelerate gastric emptying dependent on their duration of action and also act directly by stimulating satiety signals in the CNS. These effects lead to a loss of body weight. DPP‑4 inhibitors primarily elevate endogenous active GLP‑1 plasma concentrations by two- to three-fold. They are body weight neutral since only higher concentrations of GLP‑1 than those elicited by DPP‑4 inhibitors have direct effects on the CNS or on the retardation of gastrointestinal motility. Novel studies suggest beneficial cardiovascular effects of incretin-based therapies. This article gives an overview of developments in this therapeutic area.