Cholecystokinin (CCK) and related adjunct peptide therapies for the treatment of obesity and type 2 diabetes

Cholecystokinin (CCK) is a hormone secreted from I-cells of the gut, as well as neurons in the enteric and central nervous system, that binds and activates CCK-1 and CCK-2 receptors to mediate its biological actions. To date knowledge relating to the physiological significance of CCK has predominantly focused around induction of short-term satiety. However, CCK has also been highlighted to possess important actions in relation to the regulation of insulin secretion, as well as overall beta-cell function and survival. Consequently, this has led to the development of enzymatically stable, biologically active, CCK peptide analogues with proposed therapeutic promise for both obesity and type 2 diabetes. In addition, several studies have demonstrated metabolic, and therapeutically relevant, complementary biological actions of CCK with those of the incretin hormones GIP and GLP-1, as well as with amylin and leptin. Thus, stable CCK derivatives not only offer promise as potential independent weight-reducing and glucose-lowering drugs, but also as effective adjunctive therapies. This review focuses on the recent and ongoing developments of CCK in the context of new therapies for obesity and type 2 diabetes.