Incretin-based therapies for type 2 diabetes mellitus: effects on insulin resistance

Abstract

Insulin resistance has been associated with the development of type 2 diabetes, obesity, hypertension, dyslipidemia, atherosclerosis, and thus with increased cardiovascular morbidity and mortality. Insulin resistance precedes the onset of type 2 diabetes by many years. Targeting the pathophysiologic defects that characterize the onset of diabetes is more likely to achieve a durable glucose control and to delay disease progression. Incretins are gut-derived peptides that stimulate in a glucose-dependent mechanism insulin secretion and action. Glucose-like peptide 1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors both decrease fasting and postprandial glucose levels. In addition, GLP-1 analogues promote weight loss and exert a favorable effect on several cardiovascular risk factors. Data from human and experimental studies implicate that GLP-1 analogues and to a less extend DPP-4 inhibitors enhance insulin sensitivity. This review summarizes the current knowledge regarding the impact of GLP-1 analogues and DPP-4 inhibitors on insulin resistance.