Tapping incretin-based therapy for type 2 diabetes

March 2011 
Volume 41  Number 3
Pages 49 - 51
  PDF Version Available!

TWO EXCITING CATEGORIES of incretin mimetics, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, are now available to manage type 2 diabetes mellitus.1 They're called incretin mimetics because they mimic the effect of the incretin hormones. This article explains their mechanism of action and how your patient would use them. Begin by considering their major advantages over current therapy.The information about these drugs applies to adults, not children. Consult a pharmacist or the package insert for information about each drug's safety during pregnancy and breastfeeding. Consult a pharmacist, the package insert, or a comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions for these drugs.Unlike some antidiabetic drugs, these medications don't cause weight gain. DPP-4 inhibitors and GLP-1 receptor agonists are considered weight neutral because they cause neither weight gain nor loss. However, incretin mimetics frequently do cause weight loss.2 Weight loss is believed to be due to the slowing of gastric emptying, which leads to a feeling of early satiety.Also, these agents lower blood glucose levels with minimal risk of hypoglycemia: they don't act if the circulating glucose level isn't at least 70 mg/dL.2 These are major advantages because weight gain and hypoglycemia have long been the limiting adverse reactions to some pharmacologic regimens used to manage patients with type 2 diabetes.Incretin hormones are peptides secreted by the gastrointestinal tract (small intestine) in response to food. These hormones, which stimulate insulin secretion and inhibit glucagon secretion, include glucose-dependent insulinotropic polypeptide (GIP) and GLP-1. (See A closer look at the islet of Langerhans.)The incretin effect describes the increase in insulin secretion by incretin hormones (GIP and GLP-1) in response to food intake. Incretin hormones act on the endocrine pancreas to stimulate

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