title: Clinical Pharmacokinetics and Pharmacodynamics of Albiglutide.
abstract: Albiglutide is a long-acting, glucagon-like peptide-1 receptor agonist for subcutaneous administration with a recommended dose of 30-50 mg once weekly. The aim of this article is to outline the pharmacokinetic and pharmacodynamic properties of albiglutide including the clinical efficacy and safety data underlying the approval of albiglutide for the treatment of type 2 diabetes mellitus in both Europe and USA. Albiglutide is cleared from the circulation (by a mechanism partially dependent on renal function) with an elimination half-life of 5 days, allowing once-weekly administration. In the clinical trial program called HARMONY, albiglutide demonstrated placebo-corrected reductions in glycosylated hemoglobin of 0.8-1.0%. In addition, reductions in fasting plasma glucose in the range of 1.3-2.4 mmol/L compared with placebo were reported. Albiglutide caused weight reductions at a level comparable to placebo in the HARMONY trials, possibly related to limited central nervous system penetration of the large albiglutide molecule. Albiglutide demonstrated a generally favorable safety profile, although with a signal of an increased risk of pancreatitis. The well-known adverse events related to glucagon-like peptide-1 receptor activation such as nausea, diarrhea, and vomiting were less frequent with albiglutide compared with another glucagon-like peptide-1 receptor agonist, liraglutide, but slightly more frequent following treatment with albiglutide than with placebo or active comparators from other classes of anti-hyperglycemic drugs. The full risk-benefit profile for albiglutide used in treating type 2 diabetes will not be clear until reporting of the long-term cardiovascular outcome trial (HARMONY Outcome) with planned completion in 2019.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brønden
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|The Novo Nordisk Foundation Centre 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: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Copenhagen, Denmark. mch@dadlnet.dk.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. mch@dadlnet.dk.|Department of Clinical Pharmacology, Bispebjerg Hospital, Bispebjerg Bakke, 2400, Copenhagen, NV, Denmark. mch@dadlnet.dk.
authors.forename: Mikkel B
authors.initials: MB
authors.lastname: Christensen
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D011994:Recombinant Proteins; C534611:rGLP-1 protein; D052216:Glucagon-Like Peptide 1