Incretin peptides are a group of
gastrointestinal hormones that play a prominent role in the regulation of
glucose metabolism.
Incretin-based
therapies (IBTs) have recently emerged as an important treatment option for patients with
type 2 diabetes mellitus (T2DM). These
pharmaceutical agents may be specially well suited for patients who are
overweight or obese with primarily post-meal
glucose peaks, and in whom traditional first-line oral agents have failed to maintain adequate
glycemic control. There are 2 classes of IBTs: the dipeptidyl peptidase-4 (DPP-4) inhibitors and the
glucagon-like peptide 1 (GLP-1) receptor agonists. The ultimate effect of both types of agents is to augment
GLP-1 signaling, which results in enhanced
glucose-dependent insulin secretion, inhibition of
glucagon secretion and decreased appetite. This leads to improved regulation of
glucose homeostasis accompanied by either no increase in
body weight (with
DPP-4 inhibitors) or a reduction (with
GLP-1 receptor agonists).
GLP-1 inhibits food intake and the increased
GLP-1 response may contribute as a satiety signal. Although data regarding the effect of
GLP-1 agonists and
DPP-4 inhibitors on levels of
peptides involved in the regulation of food intake in T2DM are few, an indirect effect of IBT on
weight loss is possible (e.g.
Exendin-4 induces
adiponectin secretion in vitro). Results from animal models indicate reduction of food intake and
body weight by
GLP-1 agonists, but follow-up studies are required. A growing amount of evidence suggests that these
peptides may also impact the cardiovascular system, including beneficial effects on myocardial cells,
lipid profiles and blood pressure as well as reduced markers of systemic
inflammation and improved endothelial dysfunction. The potential role of these agents in improving components of the
metabolic syndrome and retardation of
atherosclerosis needs to be fully elucidated. Although IBTs are currently recommended only for use in the early treatment of T2DM, the 'non-glycemic' actions of these drugs may have far reaching therapeutic implications. It is hoped that future studies will elucidate their potential strengths and weaknesses for use in various metabolic conditions.