Drug-drug interactions with glucagon-like peptide-1 receptor agonists.

OBJECTIVE: To review drug interaction studies of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and concurrent oral medications. DATA SOURCES: 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. STUDY SELECTION AND DATA EXTRACTION: 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. DATA SYNTHESIS: 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.