Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in patients with type 2 diabetes

J Clin Endocrinol Metab. 2008 Dec;93(12):4810-7. doi: 10.1210/jc.2008-1518. Epub 2008 Sep 23.


Context: Native glucagon-like peptide-1 increases insulin secretion, decreases glucagon secretion, and reduces appetite but is rapidly inactivated by dipeptidyl peptidase-4. Albiglutide is a novel dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin designed to have sustained efficacy in vivo.

Objectives: The objectives were to investigate pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide in type 2 diabetes subjects.

Methods: In a single-blind dose-escalation study, 54 subjects were randomized to receive placebo or 9-, 16-, or 32-mg albiglutide on d 1 and 8. In a complementary study, 46 subjects were randomized to a single dose (16 or 64 mg) of albiglutide to the arm, leg, or abdomen.

Results: Significant dose-dependent reductions in 24-h mean weighted glucose [area under the curve((0-24 h))] were observed, with placebo-adjusted least squares means difference values in the 32-mg cohort of -34.8 and -56.4 mg/dl [95% confidence interval (-54.1, -15.5) and (-82.2, -30.5)] for d 2 and 9, respectively. Placebo-adjusted fasting plasma glucose decreased by -26.7 and -50.7 mg/dl [95% confidence interval (-46.3, -7.06) and (-75.4, -26.0)] on d 2 and 9, respectively. Postprandial glucose was also reduced. No hypoglycemic episodes were detected in the albiglutide cohorts. The frequency and severity of the most common adverse events, headache and nausea, were comparable with placebo controls. Albiglutide half-life ranged between 6 and 7 d. The pharmacokinetics or pharmacodynamic of albiglutide was unaffected by injection site.

Conclusions: Albiglutide improved fasting plasma glucose and postprandial glucose with a favorable safety profile in subjects with type 2 diabetes. Albiglutide's long half-life may allow for once-weekly or less frequent dosing.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Area Under Curve
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / pharmacokinetics
  • Glucagon-Like Peptide 1 / physiology*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glycated Hemoglobin / metabolism
  • Half-Life
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Molecular Mimicry
  • Young Adult


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • rGLP-1 protein
  • Glucagon-Like Peptide 1