The endogenous incretin hormones, glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released from the gastrointestinal tract after nutrient stimulation and play a major role in glucose homeostasis. Thus, incretin hormones represent a novel therapeutic target for the treatment of diabetes. In clinical studies, both exenatide and liraglutide (GLP-1 receptor agonists which are resistant to DPP-4 degradation) are known to improve β-cell function and glycemia with minimal hypoglycemia. This review aimed to examine the extraglycemic effects of the incretins and to justify the therapeutic rationale for incretin-based strategies in patients with type 2 diabetes. First of all, therapeutic agents like incretins have been shown to inhibit β-cell apoptosis and increase islet proliferation/replication. Moreover, the use of these agents was also reported to be associated with reduced body weight, and in some studies, had favourable effects on blood pressure, diabetic dyslipidemia, myocardial contractility, hepatic and endothelial function. These effects have the potential to provide a better control of glucose homeostasis and also decrease multiple cardiovascular risk factors that are observed in patients with diabetes.
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