Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1

Current therapies for type 2 diabetesare frequently associated with inad-equate control of postprandial hy-perglycemia, weight gain, and, in the case of oral agents, loss of efficacy over time. A better understanding of physiological re-sponses to meals is leading to the devel-opment of new agents whose therapeutic action is based on the enhancement of gastrointestinal hormone action. These therapies are associated with slowing of gastric emptying, stimulation of insulin and inhibition of glucagon secretion, im-proved control of postprandial hypergly-cemia, and control of body weight. This review summarizes several limitations in the treatment of type 2 diabetes and de-scribes the mechanisms of action and clinical data obtained with amylin and glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase IV (DPP-IV) inhibitors for the treatment of diabetes. Despite considerable effort by patients and physicians, the results of treating type 2 diabetes are often disappointing. This re-view examines the limitations of current an-tihyperglycemic therapies and assesses the potential of the emerging class of agents that mimic or enhance the actions of amylin and GLP-1,which are both gastrointestinal pep-tide hormones that in concert with insulin and glucagon regulate fuel homeostasis and eating behavior (1–4). Several agents from this class have been recently approved for clinical use or are in the advanced stages of development. Their mechanisms of action and therapeutic effects, as described in peer-reviewed publications, will be dis-cussed.