title: Drug-drug interactions with glucagon-like peptide-1 receptor agonists.
abstract: OBJECTIVE
  To review drug interaction studies of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and concurrent oral medications.
  
  
  METHODS
  PubMed was searched (to December 5, 2011) using the terms exenatide, liraglutide, albiglutide, and lixisenatide. The search was limited to studies published in English and conducted in adults. Abstracts from the American Diabetes Association Scientific Sessions from 2004 through 2011 were also searched.
  
  
  METHODS
  All abstracts were screened for eligibility, which consisted of studies reporting the effects of GLP-1RA administration on the pharmacokinetics and pharmacodynamics of concurrent oral medications. Data extracted from eligible trials included study and population characteristics; pharmacokinetic parameters including maximum concentration (C(max)), time to maximum concentration (t(max)), and area under the concentration-time curve (AUC); and pharmacodynamic properties.
  
  
  RESULTS
  Our search identified 254 potentially relevant articles; of those, 11 articles evaluating 15 drug interactions were reviewed. Only 1 study was conducted in patients with type 2 diabetes. Equivalence in AUC was demonstrated in the majority of drug interactions studied (11 of 15). The AUCs of acetaminophen and lovastatin were decreased after exenatide administration and those of lisinopril and digoxin were decreased after liraglutide administration. In 10 studies, GLP-1RAs decreased the C(max) and, in 14 studies, prolonged the t(max) of study drug. Pharmacokinetic properties of drugs and differences in study design can explain differences in interaction potential.
  
  
  CONCLUSIONS
  GLP-1RAs may produce clinically significant interactions with drugs that require achievement of target peak concentrations or a rapid onset of action. Studies in patients with type 2 diabetes are needed to further assess and allow comparison of several GLP-1RA agents' impact on steady-state pharmacokinetics and pharmacodynamics of concomitant oral medications.
authors.affiliation: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA. k.hurren@wayne.edu
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Hurren
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Pinelli
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004347:Drug Interactions; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055553:Prescription Drugs / Q000493:pharmacokinetics*; D018027:Receptors, Glucagon / Q000819:agonists*
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D055553:Prescription Drugs; D018027:Receptors, Glucagon