DPP-4 inhibitors and glucose control

GAGLIARDINO JJ

Dubai

Congreso; World Diabetes Congress 2011; 2011

IDF

Sustained hyperglycaemia is a feature used for the diagnosis of diabetes to estimate its degree of metabolic control; it also is an important cause of diabetes complications. In Type 2 diabetes (T2DM), hyperglycaemia is the consequence of decreased tissue sensitivity to insulin and a progressive decrease of B-cell mass/function. An inadequate secretion of glucagon, an increased liver glucose output and a marked decrease of the incretin effect upon glucose-induced insulin secretion complete its pathogenic mechanism. Patients with T2DM also have other cardiovascular risk factors (CVRF), namely obesity, hypertension and dyslipidemia, and these conditions share a common feature: glucoxidative stress (OS). Endothelial dysfunction would enhance the magnitude of the OS state. Due to the presence of low antioxidant enzyme activity, islet cells are rapidly affected by OS, establishing a vicious circle where the excessive offer of substrates, characteristic of poorly-controlled diabetes, stimulates the OS process. Glucagon like peptide-1 receptor agonists (GLP-1R) and inhibitors of dipeptidyl peptidase-4 (DPP-4i) reduce hyperglycaemia by enhancing the B-cell response to glucose and correcting the abnormal glucagon secretion. They also decrease OS at endothelial and islet level. Assuming that OS is the common factor responsible for hyperglycaemia and the other CVRF, incretins might directly affect their core pathogenic cause. Since the stimulatory effect of incretins upon insulin secretion is tightly related to blood glucose levels, they have a lower frequency of hypoglycaemia than insulin secretagogues. They also decrease or exert a neutral effect on body weight, decrease hypertriglyceridemia and contribute to lower blood pressure. These beneficial effects on body weight and triglyceride concentrations would improve insulin sensitivity. Undesirable cardiovascular effects have not been demonstrated with these agents, thus providing additional support to their potential value in the treatment of people with T2DM.