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Differential chemistry (structure), mechanism of action, and pharmacology of GLP-1 receptor agonists and DPP-4 inhibitors Neumiller JJJ Am Pharm Assoc (2003) 2009[Sep]; 49 Suppl 1 (ä): S16-29OBJECTIVE: To review the pharmacology (absorption, metabolism, distribution, elimination, and contraindications) of incretin-based agents currently available and in regulatory review for the treatment of patients with type 2 diabetes. DATA SOURCES: Medline search of all relevant clinical and review articles. STUDY SELECTION: English-language articles pertinent to the pharmacology, pharmacodynamics, pharmacokinetics, efficacy, and safety of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors were reviewed for relevance. DATA EXTRACTION: Data pertinent to the pharmacology, pharmacodynamics, pharmacokinetics, efficacy, and safety of GLP-1 agonists and DPP-4 inhibitors were extracted and used. DATA SYNTHESIS: Incretin hormones are secreted from the gastrointestinal tract following meal ingestion, the two most important of which are glucose-dependent insulinotropic polypeptide (GIP) and GLP-1. Patients with type 2 diabetes have an impaired response to GIP, while intravenous GLP-1 has been shown to increase insulin secretion in response to elevated glucose levels. Incretin-based agents include GLP-1 receptor agonists, which mimic endogenous GLP-1, and DPP-4 inhibitors (e.g., sitagliptin, vildagliptin, saxagliptin, alogliptin), which inhibit the breakdown of endogenous incretin hormones. GLP-1 receptor agonists stimulate insulin secretion in a glucose-dependent manner and suppress glucagon secretion with a low risk of hypoglycemia. The GLP-1 receptor agonists are further differentiated as either human analogues (e.g., liraglutide) or synthetic exendin-based mimetics (e.g., exenatide). These agents delay gastric emptying and may beneficially affect satiety and are thus associated with weight reduction. CONCLUSION: GLP-1 receptor agonists and DPP-4 inhibitors facilitate therapy intensification and achievement of established glycemic goals. They enhance postprandial and fasting glycemic control, and use may improve beta-cell function and possibly preserve beta-cell mass. GLP-1 receptor agonists may also have favorable effects on blood pressure. They may be introduced as adjuncts to ongoing therapy with conventional agents with a potential benefit of slowing the progression of type 2 diabetes.|*Dipeptidyl-Peptidase IV Inhibitors/adverse effects/chemistry/pharmacokinetics/*pharmacology[MESH]|Amino Acid Sequence[MESH]|Animals[MESH]|Blood Glucose/drug effects[MESH]|Diabetes Mellitus, Type 2/*drug therapy/metabolism/physiopathology[MESH]|Dipeptidyl Peptidase 4/metabolism[MESH]|Gastric Emptying/drug effects[MESH]|Glucagon-Like Peptide-1 Receptor[MESH]|Humans[MESH]|Hypoglycemic Agents/adverse effects/chemistry/pharmacokinetics/*pharmacology[MESH]|Incretins/metabolism[MESH]|Insulin-Secreting Cells/drug effects/metabolism[MESH]|Insulin/metabolism[MESH]|Molecular Sequence Data[MESH]|Molecular Structure[MESH]|Receptors, Glucagon/*agonists/metabolism[MESH]|Satiety Response/drug effects[MESH]|Structure-Activity Relationship[MESH]|Treatment Outcome[MESH]|Weight Loss/drug effects[MESH] |
