Clinical pharmacology of albiglutide, a GLP-1 receptor agonist.
Albiglutide is a glucagon-like peptide-1 analogue composed of tandem copies of modified human glucagon-like peptide-1 (7-36) coupled to recombinant human albumin that is approved in adults for the treatment of type 2 diabetes mellitus. After subcutaneous administration, albiglutide is likely primarily absorbed via the lymphatic circulation, with maximum concentrations being reached in 3 to 5 days; steady-state exposures are achieved following approximately 4 to 5 weeks of once-weekly administration. The elimination half-life of albiglutide is approximately 5 days. Clearance of albiglutide is 67 mL/h with between-subject variability of 34.9%; no covariates have been identified that would require dose adjustment of albiglutide. Albiglutide lowers the fasting plasma glucose and reduces postprandial glucose excursions. In addition, β-cell secretion is enhanced by albiglutide during hyperglycemia, whereas secretion is suppressed during hypoglycemia; α-cell response to hypoglycemia is not impaired by albiglutide. Albiglutide does not prolong the corrected QT interval but has a modest effect on heart rate in patients with type 2 diabetes mellitus. Dose adjustment is not suggested in patients with renal impairment, but experience in patients with severe renal impairment is very limited, and it is recommended that albiglutide be used with care in such patients due to an increased frequency of diarrhea, nausea, and vomiting. No clinically relevant drug interactions have been observed in clinical trials.


BACKGROUND
NCT00938158, NCT01406262, NCT00537719, NCT01077505, NCT01147731, NCT01147718, NCT01147692, NCT00354536, NCT00394030, NCT00530309, NCT01357889, NCT00518115, NCT01098461, NCT01475734, NCT00849017, NCT00838916, NCT00839527, NCT01098539.
Senior Director, Clinical Pharmacology, Modeling and Simulation, GlaxoSmithKline, Research Triangle Park, NC. malcolm.a.young@gsk.com.
Malcolm A
MA
Young
Jeffrey A
JA
Wald
Jessica E
JE
Matthews
Rhona
R
Scott
Rebecca J
RJ
Hodge
Hui
H
Zhi
Rickey R
RR
Reinhardt
D065567:Absorption, Physiological; D001786:Blood Glucose / Q000187:drug effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D054795:Incretins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D018027:Receptors, Glucagon / Q000819:agonists*; D019821:Simvastatin / Q000627:therapeutic use; D014859:Warfarin / Q000494:pharmacology
D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; C534611:rGLP-1 protein; D014859:Warfarin; D052216:Glucagon-Like Peptide 1; D019821:Simvastatin