title: Exenatide: pharmacokinetics, clinical use, and future directions.
abstract: The first-in-class glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide, which was initially approved in 2005, is available in twice-daily (BID) and once-weekly (QW) formulations. Clinical trial data suggest both formulations are effective and safe for patients with type 2 diabetes (T2D), both as monotherapy and as part of combination therapy. Since exenatide was approved, several other GLP-1RAs have become available for clinical use. Areas covered: Many ongoing clinical trials involving exenatide BID and exenatide QW are investigating new indications (exenatide BID) and new end points and combination therapies (exenatide QW). This review provides an overview of the delivery and pharmacokinetics of both formulations of exenatide, reviews existing data in T2D, and summarizes ongoing investigations. Expert opinion: Exenatide BID and QW have substantial clinical benefits. Comparisons with other GLP-1RAs demonstrate some differences in efficacy and safety profiles that make assessment of benefit:risk ratios complex. Head-to-head comparisons of QW GLP-1RA formulations may assist in the ranking of GLP-1RAs according to efficacy and safety. Results on the impact of exenatide QW on cardiovascular outcomes are eagerly awaited. The potential clinical utility of exenatide BID in other indications will clarify whether exenatide holds clinical promise in diagnoses other than T2D.
authors.affiliation: a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.|b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.|c The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.|b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brønden
authors.affiliation: a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark.|b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010455:Peptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014688:Venoms / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Exenatide; extended-release; glucagon-like peptide-1 receptor agonist; glycemic control; type 2 diabetes