Liraglutide: a once-daily incretin mimetic for the treatment of type 2 diabetes mellitus.
OBJECTIVE
To review the pharmacology, pharmacokinetics, efficacy, and safety of liraglutide, a glucagon-like peptide 1 (GLP-1) analog for the treatment of type 2 diabetes mellitus.


METHODS
A MEDLINE search (1966-May 2009) was conducted for English-language articles using the terms glucagon-like peptide 1, incretin mimetic, NN2211, and liraglutide. Abstracts presented at the American Diabetes Association and European Association for the Study of Diabetes annual meetings in 2006, 2007, and 2008 were also searched for relevant data.


METHODS
Articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of liraglutide were reviewed.


RESULTS
Liraglutide is a GLP-1 analog with pharmacokinetic properties suitable for once-daily administration. Clinical trial data from large, controlled studies demonstrate the effectiveness of liraglutide in terms of hemoglobin A(1c) (A1C) reduction, reductions in body weight, and the drug's low risk for hypoglycemic events when used as monotherapy. Data also support benefits of liraglutide therapy on beta-cell responsiveness to glucose, with animal and in vitro data indicating potential benefits in beta-cell mass and neogenesis with liraglutide treatment. Liraglutide has been studied as monotherapy and in combination with metformin, glimepiride, and rosiglitazone for the treatment of type 2 diabetes. Additionally, comparative data with insulin glargine and exenatide therapy are available from Phase 3 trials providing practitioners valuable clinical data on which to base clinical decision making. Overall, liraglutide is well tolerated with dose-dependent nausea, vomiting, and diarrhea being the most commonly reported adverse events in clinical trials.


CONCLUSIONS
Once-daily administration may provide a therapeutic advantage for liraglutide over twice-daily exenatide, with similar improvements in A1C and body weight observed when liraglutide was compared with exenatide. The glucose-dependent mechanism of insulin release with GLP-1 agonist therapy holds potential clinical significance in the management of postprandial hyperglycemic excursions, with minimal risk of hypoglycemia.
Neumiller
Joshua J
JJ
Department of Pharmacotherapy, College of Pharmacy, Washington State University/Elder Services, Spokane, WA 99217, USA. jneumiller@wsu.edu
Campbell
R Keith
RK
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D018849:Controlled Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D054795:Incretins / Q000378:metabolism; D000069450:Liraglutide
D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D000069450:Liraglutide